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Okita M, Takenaka K, Hirai F, Ashizuka S, Iijima H, Bamba S, Fujii T, Watanabe K, Shimodaira Y, Shiga H, Hiraoka S, Inokuchi T, Yamamura T, Emoto R, Matsui S. Diagnostic accuracy and cut-off values of serum leucine-rich alpha-2 glycoprotein for Crohn's disease activity in the small bowel. J Gastroenterol 2025; 60:573-582. [PMID: 39953247 PMCID: PMC12014797 DOI: 10.1007/s00535-025-02223-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Accepted: 01/25/2025] [Indexed: 02/17/2025]
Abstract
BACKGROUND Small bowel (SB) lesions in Crohn's disease (CD) are often asymptomatic despite being highly active. Fecal calprotectin (FC) is the most widely used biomarker of CD activity, but its drawbacks include a large intra-individual sample variability and the burden of collecting stool samples. Meanwhile, serum leucine-rich alpha-2 glycoprotein (LRG) has recently attracted attention as a biomarker that can address the limitations of FC. This study determined the diagnostic accuracy of LRG and its cut-off values for diagnosing CD activity in SB. METHODS This was a retrospective, multi-center study of CD patients undergoing retrograde balloon-assisted endoscopy. For ileal- and ileocolonic-type patients with a colon SES-CD score of 0, we estimated the receiver operating characteristic curve of LRG and determined the cut-off value to achieve a target sensitivity level of 80%. RESULTS Among 285 patients with SB lesions, LRG had an area under the curve (AUC) of 0.72 (95% CI 0.67-0.78) with a sensitivity of 80.2% and specificity of 47.2% for a cut-off value of 10.5 when diagnosing endoscopic remission (modified SES-CD ≤ 3), while it had an AUC of 0.72 (95% CI 0.65-0.78) with a sensitivity of 81.2% and specificity of 46.2% for a cut-off value of 10.1 when diagnosing complete ulcer healing (modified SES-CD ≤ 1). CONCLUSION LRG was effective for diagnosing CD activity in SB, specifically with cut-off values of 10.5 and 10.1 for endoscopic remission and complete ulcer healing, respectively. A future prospective validation study will assess its clinical utility.
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Affiliation(s)
- Muneyori Okita
- Department of Biostatistics, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
| | - Kento Takenaka
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Fumihito Hirai
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Fukuoka, Japan
| | - Shinya Ashizuka
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Fukuoka, Japan
| | - Hideki Iijima
- Osaka International Medical & Science Center, Osaka Keisatsu Hospital, Osaka, Japan
| | - Shigeki Bamba
- Department of Fundamental Nursing, Shiga University of Medical Science, Shiga, Japan
| | - Toshimitsu Fujii
- Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan
| | - Kenji Watanabe
- Department of Internal Medicine for Inflammatory Bowel Disease, Toyama University, Toyama, Japan
| | - Yosuke Shimodaira
- Department of Gastroenterology and Neurology, Akita University Graduate School of Medicine, Akita, Japan
| | - Hisashi Shiga
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Sakiko Hiraoka
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan
| | - Toshihiro Inokuchi
- Research Center for Intestinal Health Science, Okayama University, Okayama, Japan
| | - Takeshi Yamamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Ryo Emoto
- Department of Biostatistics, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Shigeyuki Matsui
- Department of Biostatistics, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan
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Edwards TS, Ho SSC, Brown SC, Appleton L, Smith BR, Borichevsky GM, Swaminathan A, Frampton CMA, Gearry RB, Kettle AJ, Day AS. Fecal Myeloperoxidase Levels Reflect Disease Activity in Children With Crohn's Disease. Inflamm Bowel Dis 2025; 31:800-811. [PMID: 39527499 PMCID: PMC11879223 DOI: 10.1093/ibd/izae262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Crohn's disease (CD) is a major form of inflammatory bowel disease (IBD) which has relapsing and remitting symptoms. Better ways to detect and monitor active disease are required for early diagnosis and optimal outcomes. We assessed fecal myeloperoxidase (fMPO), a neutrophil-derived enzyme that produces hypochlorous acid, as a marker of disease activity in children with CD. METHODS This observational study assessed myeloperoxidase (MPO) levels in fecal samples from children aged <17 years with CD (51 with active or 42 inactive disease) measured by enzyme-linked immunosorbent assay (ELISA) and compared to controls (35 healthy siblings and 15 unrelated well children). Results were correlated with fecal calprotectin, serum C-reactive protein, urinary glutathione sulfonamide (a biomarker of hypochlorous acid), and disease activity scores. Differences between groups were assessed by analysis of variance. Receiver-operating-characteristic curves were used to assess how biomarkers predicted disease and disease activity. RESULTS Fecal myeloperoxidase activity and fMPO protein correlated with fecal calprotectin (r = 0.78, P < .0001, and r = 0.81, P < .0001, respectively). Fecal myeloperoxidase activity and protein levels were significantly higher (P ≤ .0001) in individuals with active disease compared to healthy sibling controls, unrelated well children, and those with inactive disease. A 9.7 µg/g fMPO protein cutoff distinguished inactive from active disease (sensitivity = 75%, specificity = 76%). Urinary GSA was elevated in children with active disease (P < .0001) and correlated with fMPO protein (r = 0.43, P = .0002) in a subset of 72 children with IBD and controls. CONCLUSIONS Fecal myeloperoxidase may be superior to fCal at reflecting disease severity in children with CD and produces the damaging oxidant hypochlorous acid during active inflammation.
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Affiliation(s)
- Teagan S Edwards
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
| | - Shaun S C Ho
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
- Department of Gastroenterology and Clinical Nutrition, The Royal Children’s Hospital Melbourne, Melbourne, Victoria, Australia
- Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
- Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
| | - Stephanie C Brown
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
| | - Laura Appleton
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
| | - Briana R Smith
- Department of Pathology and Biomedical Sciences, Mātai Hāora—Centre for Redox Biology and Medicine, University of Otago, Christchurch, New Zealand
| | - Grace M Borichevsky
- Department of Pathology and Biomedical Sciences, Mātai Hāora—Centre for Redox Biology and Medicine, University of Otago, Christchurch, New Zealand
| | | | | | - Richard B Gearry
- Department of Medicine, University of Otago, Christchurch, New Zealand
- Department of Gastroenterology, Christchurch Hospital, Christchurch, New Zealand
| | - Anthony J Kettle
- Department of Pathology and Biomedical Sciences, Mātai Hāora—Centre for Redox Biology and Medicine, University of Otago, Christchurch, New Zealand
| | - Andrew S Day
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
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Ojaghi Shirmard F, Pourfaraji SM, Saeedian B, Bagheri T, Ismaiel A, Matsumoto S, Babajani N. The usefulness of serum leucine-rich alpha-2 glycoprotein as a novel biomarker in monitoring inflammatory bowel disease: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2025:00042737-990000000-00488. [PMID: 39976047 DOI: 10.1097/meg.0000000000002952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
Inflammatory bowel disease (IBD) is a condition of unknown origin. It does not have a definite cure and its response to various treatments can be evaluated based on symptom-based measures, invasive procedures, or biomarker levels, highlighting the need for an accurate biomarker. Since C-reactive protein (CRP) and fecal calprotectin have their shortcomings, the need for a novel biomarker remains critical. Systematic searches of PubMed, Scopus, Web of Science, and Embase were performed In January 2024. PROSPERO number is CRD42024507383. We assessed the accuracy of leucine-rich alpha-2 glycoprotein (LRG) in identifying disease activity among patients with IBD using a bivariate diagnostic random-effects model. Fourteen studies involving 1794 individuals conducted in Japan were selected for our systematic review. The sensitivity and specificity of LRG levels for detecting disease activity were analyzed in patients with IBD and in two subgroups (ulcerative colitis and Crohn's disease). The synthesized sensitivity and specificity were 75.4% [95% confidence interval (CI), 68.9-80.9%] and 77.3% (95% CI, 69.9-83.2%), respectively, in patients with IBD, 73.1% (95% CI, 62.7-81.5%) and 81.9% (95% CI, 73.9-87.8%), respectively, in patients with CD, and the secondary analysis of the ulcerative colitis subgroup showed a pooled sensitivity and specificity of 72.8 and 59.7%, respectively. Our systematic review and meta-analysis demonstrated that LRG could be useful in detecting IBD activity. It is superior for detecting disease activity, especially in patients with normal CRP levels. The LRG was more accurate in monitoring disease activity in patients with CD than in patients with IBD.
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Affiliation(s)
| | | | - Behrad Saeedian
- School of Medicine
- Digestive Diseases Research Institute (DDRI), Tehran University of Medical Sciences, Tehran, Iran
| | | | - Abdulrahman Ismaiel
- 2nd Department of Internal Medicine, 'Iuliu Hatieganu' University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Satohiro Matsumoto
- Department of Gastroenterology, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - Nastaran Babajani
- School of Medicine
- Digestive Diseases Research Institute (DDRI), Tehran University of Medical Sciences, Tehran, Iran
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Caetano‐Silva ME, Shrestha A, Duff AF, Kontic D, Brewster PC, Kasperek MC, Lin C, Wainwright DA, Hernandez‐Saavedra D, Woods JA, Bailey MT, Buford TW, Allen JM. Aging amplifies a gut microbiota immunogenic signature linked to heightened inflammation. Aging Cell 2024; 23:e14190. [PMID: 38725282 PMCID: PMC11320341 DOI: 10.1111/acel.14190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 04/20/2024] [Accepted: 04/22/2024] [Indexed: 08/15/2024] Open
Abstract
Aging is associated with low-grade inflammation that increases the risk of infection and disease, yet the underlying mechanisms remain unclear. Gut microbiota composition shifts with age, harboring microbes with varied immunogenic capacities. We hypothesized the gut microbiota acts as an active driver of low-grade inflammation during aging. Microbiome patterns in aged mice strongly associated with signs of bacterial-induced barrier disruption and immune infiltration, including marked increased levels of circulating lipopolysaccharide (LPS)-binding protein (LBP) and colonic calprotectin. Ex vivo immunogenicity assays revealed that both colonic contents and mucosa of aged mice harbored increased capacity to activate toll-like receptor 4 (TLR4) whereas TLR5 signaling was unchanged. We found patterns of elevated innate inflammatory signaling (colonic Il6, Tnf, and Tlr4) and endotoxemia (circulating LBP) in young germ-free mice after 4 weeks of colonization with intestinal contents from aged mice compared with young counterparts, thus providing a direct link between aging-induced shifts in microbiota immunogenicity and host inflammation. Additionally, we discovered that the gut microbiota of aged mice exhibited unique responses to a broad-spectrum antibiotic challenge (Abx), with sustained elevation in Escherichia (Proteobacteria) and altered TLR5 immunogenicity 7 days post-Abx cessation. Together, these data indicate that old age results in a gut microbiota that differentially acts on TLR signaling pathways of the innate immune system. We found that these age-associated microbiota immunogenic signatures are less resilient to challenge and strongly linked to host inflammatory status. Gut microbiota immunogenic signatures should be thus considered as critical factors in mediating chronic inflammatory diseases disproportionally impacting older populations.
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Affiliation(s)
- Maria Elisa Caetano‐Silva
- Department of Health and KinesiologyUniversity of Illinois at Urbana‐ChampaignUrbanaIllinoisUSA
- Division of Nutritional SciencesUniversity of Illinois at Urbana ChampaignUrbanaIllinoisUSA
| | - Akriti Shrestha
- Division of Nutritional SciencesUniversity of Illinois at Urbana ChampaignUrbanaIllinoisUSA
| | - Audrey F. Duff
- Center for Microbial PathogenesisNationwide Children's HospitalColumbusOhioUSA
| | - Danica Kontic
- Center for Microbial PathogenesisNationwide Children's HospitalColumbusOhioUSA
| | - Patricia C. Brewster
- Department of Health and KinesiologyUniversity of Illinois at Urbana‐ChampaignUrbanaIllinoisUSA
| | - Mikaela C. Kasperek
- Division of Nutritional SciencesUniversity of Illinois at Urbana ChampaignUrbanaIllinoisUSA
| | - Chia‐Hao Lin
- Department of Health and KinesiologyUniversity of Illinois at Urbana‐ChampaignUrbanaIllinoisUSA
| | - Derek A. Wainwright
- Departments of Cancer Biology and Neurological SurgeryLoyola University Chicago, Stritch School of MedicineMaywoodIllinoisUSA
| | - Diego Hernandez‐Saavedra
- Department of Health and KinesiologyUniversity of Illinois at Urbana‐ChampaignUrbanaIllinoisUSA
- Division of Nutritional SciencesUniversity of Illinois at Urbana ChampaignUrbanaIllinoisUSA
| | - Jeffrey A. Woods
- Department of Health and KinesiologyUniversity of Illinois at Urbana‐ChampaignUrbanaIllinoisUSA
- Division of Nutritional SciencesUniversity of Illinois at Urbana ChampaignUrbanaIllinoisUSA
| | - Michael T. Bailey
- Center for Microbial PathogenesisNationwide Children's HospitalColumbusOhioUSA
| | - Thomas W. Buford
- Division of Gerontology, Geriatrics and Palliative Care, Department of MedicineUniversity of Alabama at BirminghamBirminghamAlabamaUSA
- Birmingham/Atlanta VA GRECCBirmingham VA Medical CenterBirminghamAlabamaUSA
| | - Jacob M. Allen
- Department of Health and KinesiologyUniversity of Illinois at Urbana‐ChampaignUrbanaIllinoisUSA
- Division of Nutritional SciencesUniversity of Illinois at Urbana ChampaignUrbanaIllinoisUSA
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Edwards TS, Day AS. The role of fecal biomarkers in individuals with inflammatory bowel disease. Expert Rev Mol Diagn 2024; 24:497-508. [PMID: 38995110 DOI: 10.1080/14737159.2024.2375224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 06/28/2024] [Indexed: 07/13/2024]
Abstract
INTRODUCTION Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and Ulcerative Colitis (UC), is a relapsing and remitting condition. Noninvasive biomarkers have an increasingly important role in the diagnosis of IBD and in the prediction of future disease course in individuals with IBD. Strategies for the management of IBD increasingly rely upon close monitoring of gastrointestinal inflammation. AREAS COVERED This review provides an update on the current understanding of established and novel stool-based biomarkers in the diagnosis and management of IBD. It also highlights key gaps, identifies limitations, and advantages of current markers, and examines aspects that require further study and analysis. EXPERT OPINION Current noninvasive inflammatory markers play an important role in the diagnosis and management of IBD; however, limitations exist. Future work is required to further characterize and validate current and novel markers of inflammation. In addition, it is essential to better understand the roles and characteristics of noninvasive markers to enable the appropriate selection to accurately determine the condition of the intestinal mucosa.
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Affiliation(s)
- Teagan S Edwards
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand
| | - Andrew S Day
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand
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Okita M, Nakashima K, Yamamura T, Matsui S. Systematic Review and Meta-Analysis of the Use of Serum Leucine-Rich Alpha-2 Glycoprotein to Assess Crohn's Disease Activity. Inflamm Bowel Dis 2024; 30:780-787. [PMID: 37506169 DOI: 10.1093/ibd/izad128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Indexed: 07/30/2023]
Abstract
BACKGROUND Although fecal calprotectin is the most widely used biomarker for assessing Crohn's disease activity, serum leucine-rich alpha-2 glycoprotein has recently attracted attention, especially in Japan. Here we performed a systematic review and meta-analysis of serum leucine-rich alpha-2 glycoprotein to obtain evidence for its accuracy in assessing Crohn's disease activity. METHODS On February 1, 2023, we performed searches of PubMed, Web of Science, and CENTRAL. The Prospero number is CRD42023396034. The primary outcomes were the sensitivity and specificity of serum leucine-rich alpha-2 glycoprotein for assessing Crohn's disease activity. We used a bivariate generalized linear mixed model, assuming a binomial distribution at the test level and a bivariate normal distribution at the between-test level. RESULTS We selected 9 studies involving 797 individuals in our systematic review. Regarding the primary outcomes, the synthesized sensitivity and specificity of serum leucine-rich alpha-2 glycoprotein were 77.0% (95% confidence interval, 67.8% to 84.2%) and 81.1% (95% confidence interval, 72.6% to 87.4%), respectively. The area under the curve was 0.86, and the partial area under the curve was 0.78. Regarding between-study heterogeneity, both the I2 value by Zhou and Dendukuri approach and the I2 value by Holling sample size-adjusted approaches were 0%. CONCLUSIONS Our systematic review and meta-analysis of serum leucine-rich alpha-2 glycoprotein demonstrated its accuracy in assessing Crohn's disease activity. Further studies are needed to demonstrate its clinical utility and clinical validity.
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Affiliation(s)
- Muneyori Okita
- Department of Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Keita Nakashima
- Department of Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takeshi Yamamura
- Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shigeyuki Matsui
- Department of Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Manthey C, Super M, Cepon-Robins TJ. Childhood developmental environment affects adult intestinal inflammation levels: preliminary evidence from older adults in the United States. Ann Hum Biol 2024; 51:2427593. [PMID: 39638766 DOI: 10.1080/03014460.2024.2427593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 07/24/2024] [Accepted: 09/23/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND The Old Friends Hypothesis suggests limited exposure to symbionts during development leads to immune system dysregulation (e.g. allergies, autoimmunity) and inflammatory conditions (e.g. inflammatory bowel disease), with likely sex-specific variation based on exposure risk and sex hormones. Limited research documents how variation in childhood exposures affect older adult health. AIM We tested relationships between current intestinal inflammation and childhood environment in 84 older adults (51-88 years) living in Colorado, USA. SUBJECTS AND METHODS Faecal calprotectin (FC), a biomarker of intestinal inflammation, was measured from stool samples. Structured interviews assessed farm animal exposure during childhood and childhood environments (urban, suburban, rural) at different age periods (0 to 5, 5 to 10, 10 to 20 years). RESULTS AND CONCLUSIONS Farm animal exposure was not significantly associated with FC. Females who grew up in suburban environments, especially between the ages of 5 and 10, had higher FC than females from urban or rural environments (p < 0.05). Males living in urban environments between the ages of 10 and 20 had the lowest FC compared to both other environments (p < 0.05). We found mixed, age- and sex-specific support for the idea that childhood exposures alter risk of inflammatory disease later in life.
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Affiliation(s)
- Courtney Manthey
- Anthropology Department, University of Colorado Colorado Springs, Colorado Springs, CO, USA
- Anthropology Department, University of Montana, Missoula, MT, USA
| | - Meg Super
- Biology Department, University of Colorado Colorado Springs, Colorado Springs, CO, USA
| | - Tara J Cepon-Robins
- Anthropology Department, University of Colorado Colorado Springs, Colorado Springs, CO, USA
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Carnazzo V, Redi S, Basile V, Natali P, Gulli F, Equitani F, Marino M, Basile U. Calprotectin: two sides of the same coin. Rheumatology (Oxford) 2024; 63:26-33. [PMID: 37603715 PMCID: PMC10765140 DOI: 10.1093/rheumatology/kead405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 07/09/2023] [Accepted: 07/16/2023] [Indexed: 08/23/2023] Open
Abstract
Calprotectin (CLP) is a calcium-binding protein produced by neutrophils and monocytes in the course of inflammation. Today, the role of faecal CLP in chronic IBD is well known, but in recent years attention has shifted towards circulating CLP. In fact, this molecule can be measured in different biological fluids: blood, saliva and urine, using different analytic methods that are described in this review. Furthermore, different data confirm the relevant role of serum CLP in autoimmune diseases. In this review we will highlight the correlation between high levels of circulating CLP and specific autoantibodies of major autoimmune pathologies paving the way to the employment of CLP measurement as useful biomarker for monitoring outcome in different pathologies.
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Affiliation(s)
- Valeria Carnazzo
- Department of Clinical Pathology, Santa Maria Goretti Hospital, AUSL Latina, Latina, Italy
| | - Serena Redi
- Department of Clinical Pathology, Santa Maria Goretti Hospital, AUSL Latina, Latina, Italy
- Facoltà di medicina e Chirurgia, Department of Clinical Pathology, Università “La Sapienza”, Rome, Italy
| | - Valerio Basile
- Clinical Pathology Unit and Cancer Biobank, Department of Research and Advanced Technologies, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Patrizia Natali
- Department of Laboratory Medicine and Pathology, Azienda Ospedaliero Universitaria e Azienda Unità Sanitaria Locale di Modena, Modena, Italy
| | - Francesca Gulli
- Clinical Biochemistry Laboratory, IRCCS “Bambino Gesù” Children’s Hospital, Rome, Italy
| | - Francesco Equitani
- Department of Transfusion Medicine and Immuno-Hematology, Santa Maria Goretti Hospital, AUSL Latina, Latina, Italy
| | - Mariapaola Marino
- Dipartimento di Medicina e Chirurgia Traslazionale, Sezione di Patologia Generale, Università Cattolica del Sacro Cuore, Rome, Italy
- Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome, Italy
| | - Umberto Basile
- Department of Clinical Pathology, Santa Maria Goretti Hospital, AUSL Latina, Latina, Italy
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Kapel N, Ouni H, Benahmed NA, Barbot-Trystram L. Fecal Calprotectin for the Diagnosis and Management of Inflammatory Bowel Diseases. Clin Transl Gastroenterol 2023; 14:e00617. [PMID: 37440723 PMCID: PMC10522095 DOI: 10.14309/ctg.0000000000000617] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 06/13/2023] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open
Abstract
Calprotectin is a heterodimeric calcium- and zinc-binding protein mainly derived from the cytoplasm of neutrophils that has direct antimicrobial functions and a role in the regulation of the innate immune response. It can be found in various biological compartments, in particular, the stool, with concentrations related to the level of mucosal inflammation. The measurement of fecal calprotectin has thus been recognized as a useful surrogate marker to distinguish patients with inflammatory bowel disease from those with irritable bowel syndrome. Moreover, it allows the monitoring of intestinal inflammation with a high negative predictive value, making it possible to exclude the diagnosis of inflammatory bowel disease for symptomatic patients. It also shows high sensitivity for the identification of patients requiring additional examinations for diagnosis, such as colonoscopy, and the evaluation of therapeutic responses, providing evidence of relapse or mucosal healing, which can lead to the intensification or reduction of treatment. As calprotectin levels are a measure of mucosal inflammation, high fecal concentrations are also found in other diseases with an inflammatory component, such as infectious enteritis or colorectal cancer. Interpretation of the concentration must therefore always take into account the clinical history and symptoms specific to each patient.
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Affiliation(s)
- Nathalie Kapel
- Laboratoire de Coprologie Fonctionnelle, Laboratoire de Biologie Médicale de Référence «Exploration Biochimique des Selles (Phénotype)», AP–HP, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Paris, France
- INSERM UMR-S1139, Faculté de Pharmacie, Université de Paris Cité, Paris, France
| | - Hamza Ouni
- Laboratoire de Coprologie Fonctionnelle, Laboratoire de Biologie Médicale de Référence «Exploration Biochimique des Selles (Phénotype)», AP–HP, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Paris, France
| | - Nacer Adam Benahmed
- Laboratoire de Coprologie Fonctionnelle, Laboratoire de Biologie Médicale de Référence «Exploration Biochimique des Selles (Phénotype)», AP–HP, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Paris, France
| | - Laurence Barbot-Trystram
- Laboratoire de Coprologie Fonctionnelle, Laboratoire de Biologie Médicale de Référence «Exploration Biochimique des Selles (Phénotype)», AP–HP, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Paris, France
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Witarto BS, Visuddho V, Witarto AP, Sampurna MTA, Irzaldy A. Performance of fecal S100A12 as a novel non-invasive diagnostic biomarker for pediatric inflammatory bowel disease: a systematic review and meta-analysis. J Pediatr (Rio J) 2023; 99:432-442. [PMID: 37094752 PMCID: PMC10492162 DOI: 10.1016/j.jped.2023.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 03/18/2023] [Accepted: 03/20/2023] [Indexed: 04/26/2023] Open
Abstract
OBJECTIVE The incidence and prevalence of inflammatory bowel disease (IBD) in pediatric patients are increasing. Currently, the diagnostic method for IBD is inconvenient, expensive, and difficult. S100A12, a type of calcium-binding protein, detected in the feces of patients with IBD has recently been suggested as a promising diagnostic tool. Hence, the authors aimed to evaluate the accuracy of fecal S100A12 in diagnosing IBD in pediatric patients by performing a meta-analysis. METHODS The authors performed a systematic literature search in five electronic databases for eligible studies up to July 15, 2021. Pooled diagnostic accuracies of fecal S100A12 were analyzed as the primary outcomes. Secondary outcomes were standardized mean difference (SMD) of fecal S100A12 levels between IBD and non-IBD groups and a comparison of diagnostic accuracies between fecal S100A12 and fecal calprotectin. RESULTS Seven studies comprising 712 children and adolescents (474 non-IBD controls and 238 IBD cases) were included. Fecal S100A12 levels were higher in the IBD group than in the non-IBD group (SMD = 1.88; 95% confidence interval [CI] = 1.19-2.58; p < 0.0001). Fecal S100A12 could diagnose IBD in pediatric patients with a pooled sensitivity of 95% (95% CI = 88%-98%), specificity of 97% (95% CI = 95%-98%), and area under the receiver operating summary characteristics (AUSROC) curve of 0.99 (95% CI = 0.97-0.99). Fecal S100A12 specificity and AUSROC curve values were higher than those of fecal calprotectin (p < 0.05). CONCLUSION Fecal S100A12 may serve as an accurate and non-invasive tool for diagnosing pediatric IBD.
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Affiliation(s)
| | - Visuddho Visuddho
- Universitas Airlangga, Faculty of Medicine, Medical Program, Surabaya, Indonesia
| | | | - Mahendra Tri Arif Sampurna
- Universitas Airlangga, Airlangga Teaching Hospital, Faculty of Medicine, Department of Pediatrics, Surabaya, Indonesia; Universitas Airlangga, Dr. Soetomo General Hospital, Faculty of Medicine, Department of Pediatrics, Surabaya, Indonesia.
| | - Abyan Irzaldy
- University Medical Center Rotterdam, Department of Public Health, Erasmus MC, Rotterdam, the Netherlands
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11
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Barni S, Mori F, Giovannini M, Liotti L, Mastrorilli C, Pecoraro L, Saretta F, Castagnoli R, Arasi S, Caminiti L, Gelsomino M, Klain A, del Giudice MM, Novembre E. Allergic Proctocolitis: Literature Review and Proposal of a Diagnostic-Therapeutic Algorithm. Life (Basel) 2023; 13:1824. [PMID: 37763228 PMCID: PMC10533178 DOI: 10.3390/life13091824] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 08/22/2023] [Accepted: 08/25/2023] [Indexed: 09/29/2023] Open
Abstract
Allergic proctocolitis (AP) is a benign condition, frequent in childhood, that is classified as a non-IgE-mediated food allergy. The prevalence is unknown; however, its frequency appears to be increasing, especially in exclusively breastfed infants. Clinical manifestations typically begin in the first few months of life with the appearance of bright red blood (hematochezia), with or without mucus, in the stool of apparently healthy, thriving infants. Most cases of AP are caused by cow's milk proteins; however, other allergens, such as soy, egg, corn, and wheat, may be potential triggers. Diagnosis is based on the patient's clinical history and on the resolution of signs and symptoms with the elimination of the suspected food antigen from the diet and their reappearance when the food is reintroduced into the diet. The treatment of AP is based on an elimination diet of the trigger food, with resolution of the symptoms within 72-96 h from the beginning of the diet. The prognosis of AP is good; it is a self-limiting condition, because most children can tolerate the trigger food within one year of life, with an excellent long-term prognosis. The purpose of this review is to provide an update on the current knowledge and recommendations in epidemiological, diagnostic, and therapeutic terms to the pediatricians, allergists, and gastroenterologists who may find themselves managing a patient with AP.
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Affiliation(s)
- Simona Barni
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy; (S.B.); (F.M.); (M.G.); (E.N.)
| | - Francesca Mori
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy; (S.B.); (F.M.); (M.G.); (E.N.)
| | - Mattia Giovannini
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy; (S.B.); (F.M.); (M.G.); (E.N.)
- Department of Health Sciences, University of Florence, 50139 Florence, Italy
| | - Lucia Liotti
- Pediatric Unit, Department of Mother and Child Health, Salesi Children’s Hospital, 60123 Ancona, Italy;
| | - Carla Mastrorilli
- Pediatric and Emergency Department, Pediatric Hospital Giovanni XXIII, AOU Policlinic of Bari, 70126 Bari, Italy;
| | - Luca Pecoraro
- Pediatric Unit, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, 37126 Verona, Italy;
| | - Francesca Saretta
- Pediatric Department, Latisana-Palmanova Hospital, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy;
| | - Riccardo Castagnoli
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy;
- Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Stefania Arasi
- Translational Research in Pediatric Specialties Area, Division of Allergy, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy;
| | - Lucia Caminiti
- Allergy Unit, Department of Pediatrics, AOU Policlinico Gaetano Martino, 98124 Messina, Italy;
| | - Mariannita Gelsomino
- Department of Life Sciences and Public Health, Pediatric Allergy Unit, University Foundation Policlinico Gemelli IRCCS, Catholic University of the Sacred Heart, 00168 Rome, Italy
| | - Angela Klain
- Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.K.); (M.M.d.G.)
| | - Michele Miraglia del Giudice
- Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.K.); (M.M.d.G.)
| | - Elio Novembre
- Allergy Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy; (S.B.); (F.M.); (M.G.); (E.N.)
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12
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Murray J, Kok KB, Ayling RM. Fecal Calprotectin in Gastrointestinal Disease. Clin Chem 2023:7179811. [PMID: 37228058 DOI: 10.1093/clinchem/hvad051] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 03/14/2023] [Indexed: 05/27/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) comprises a group of chronic conditions characterized by relapsing and remitting inflammation of the gastrointestinal tract. The incidence is increasing worldwide, and the therapeutic options for management are expanding. Endoscopy is the gold standard investigation for diagnosis of IBD and for assessing mucosal healing, which is increasingly being used as a measure of disease control. However, it is an invasive procedure that is unpleasant for patients and expensive and time-consuming for hospitals. Fecal calprotectin has been shown to be an accurate surrogate marker of gastrointestinal inflammation in IBD. CONTENT Fecal calprotectin was initially used for the diagnosis of IBD but is now recognized as having a role in assisting in assessment of disease activity, prediction of relapse, and informing decisions around therapy and may help to minimize requirement for endoscopy. However, there are various preanalytical and analytical factors that can affect interpretation of the results; these need to be understood to optimize clinical care. SUMMARY Preanalytical and analytical factors that can potentially influence fecal calprotectin concentrations are examined, and an overview is provided of clinical situations in which fecal calprotectin is commonly measured.
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Affiliation(s)
- Jennifer Murray
- Department of Gastroenterology, Barts Health NHS Trust, Royal London Hospital, London, United Kingdom
| | - Klaartje B Kok
- Department of Gastroenterology, Barts Health NHS Trust, Royal London Hospital, London, United Kingdom
| | - Ruth M Ayling
- Department of Clinical Biochemistry, Barts Health NHS Trust, Royal London Hospital, London, United Kingdom
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13
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Kawamura T, Yamamura T, Nakamura M, Maeda K, Sawada T, Ishikawa E, Iida T, Mizutani Y, Ishikawa T, Kakushima N, Furukawa K, Ohno E, Honda T, Kawashima H, Ishigami M. Accuracy of Serum Leucine-Rich Alpha-2 Glycoprotein in Evaluating Endoscopic Disease Activity in Crohn's Disease. Inflamm Bowel Dis 2023; 29:245-253. [PMID: 35436345 DOI: 10.1093/ibd/izac076] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND Mucosal healing, confirmed by endoscopic evaluation, is the long-term goal of treatment for Crohn's disease (CD). Leucine-rich alpha-2 glycoprotein (LRG) is a new serum biomarker correlated with disease activity in inflammatory bowel disease. However, studies evaluating its relationship with CD, particularly in the context of small intestinal lesions, are scarce. The aim of this study was to investigate the accuracy of LRG in assessing endoscopic activity, especially remission, in patients with CD. METHODS Between July 2020 and March 2021, 72 patients with CD who underwent LRG testing and double-balloon endoscopy at the same time were included. Endoscopic activity was evaluated using the applied Simple Endoscopic Score for Crohn's disease, including small intestine lesions. The relationship of LRG with clinical symptoms and endoscopic activity was assessed, and its predictive accuracy was evaluated. RESULTS Leucine-rich alpha-2 glycoprotein showed a significant positive correlation with endoscopic activity (r = 0.619, P < .001), even in patients with active lesions in the small intestine (r = 0.626, P < .001). Multivariate logistic regression revealed that LRG was the only factor associated with endoscopic remission. An LRG cutoff value of 8.9 μg/mL had a sensitivity of 93.3%; specificity of 83.3%; positive predictive value of 96.6%; negative predictive value of 71.4%; accuracy of 91.7%; and area under the curve of 0.904 for the prediction of endoscopic remission. CONCLUSIONS Leucine-rich alpha-2 glycoprotein can be used in assessing endoscopic activity and is a reliable marker of endoscopic remission in CD patients. It can be an intermediate target in the treatment of CD.
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Affiliation(s)
- Tatsuya Kawamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Takeshi Yamamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Masanao Nakamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Keiko Maeda
- Department of Endoscopy, Nagoya University Hospital, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Tsunaki Sawada
- Department of Endoscopy, Nagoya University Hospital, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Eri Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Tadashi Iida
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Yasuyuki Mizutani
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Takuya Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Naomi Kakushima
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Kazuhiro Furukawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Eizaburo Ohno
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Hiroki Kawashima
- Department of Endoscopy, Nagoya University Hospital, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
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14
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Jendraszak M, Gałęcka M, Kotwicka M, Schwiertz A, Regdos A, Pazgrat-Patan M, Andrusiewicz M. Impact of Biometric Patient Data, Probiotic Supplementation, and Selected Gut Microorganisms on Calprotectin, Zonulin, and sIgA Concentrations in the Stool of Adults Aged 18-74 Years. Biomolecules 2022; 12:biom12121781. [PMID: 36551209 PMCID: PMC9775524 DOI: 10.3390/biom12121781] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 11/25/2022] [Accepted: 11/28/2022] [Indexed: 12/02/2022] Open
Abstract
Alterations to the intestinal barrier may be involved in the pathogenesis of various chronic diseases. The diagnosis of mucosal barrier disruption has become a new therapeutic target for disease prevention. The aim of this study was to determine whether various patient demographic and biometric data, often not included in diagnostic analyses, may affect calprotectin, zonulin, and sIgA biomarker values. Stool markers' levels in 160 samples were measured colorimetrically. The analysis of twenty key bacteria (15 genera and 5 species) was carried out on the basis of diagnostic tests, including cultures and molecular tests. The concentrations of selected markers were within reference ranges for most patients. The sIgA level was significantly lower in participants declaring probiotics supplementation (p = 0.0464). We did not observe differences in gastrointestinal discomfort in participants. We found significant differences in the sIgA level between the 29-55 years and >55 years age-related intervals groups (p = 0.0191), together with a significant decreasing trend (p = 0.0337) in age-dependent sIgA concentration. We observed complex interdependencies and relationships between their microbiota and the analyzed biomarkers. For correct clinical application, standardized values of calprotectin and sIgA should be determined, especially in elderly patients. We observed a correlation between the composition of the gut community and biomarker levels, although it requires further in-depth analysis.
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Affiliation(s)
- Magdalena Jendraszak
- Chair and Department of Cell Biology, Poznan University of Medical Sciences, Rokietnicka 5D, 60-806 Poznań, Poland
- Correspondence: (M.J.); (M.A.)
| | | | - Małgorzata Kotwicka
- Chair and Department of Cell Biology, Poznan University of Medical Sciences, Rokietnicka 5D, 60-806 Poznań, Poland
| | | | | | | | - Mirosław Andrusiewicz
- Chair and Department of Cell Biology, Poznan University of Medical Sciences, Rokietnicka 5D, 60-806 Poznań, Poland
- Correspondence: (M.J.); (M.A.)
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15
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A Clinical Outcome of the Anti-PD-1 Therapy of Melanoma in Polish Patients Is Mediated by Population-Specific Gut Microbiome Composition. Cancers (Basel) 2022; 14:cancers14215369. [PMID: 36358789 PMCID: PMC9653730 DOI: 10.3390/cancers14215369] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 10/25/2022] [Accepted: 10/27/2022] [Indexed: 11/06/2022] Open
Abstract
The gut microbiota is considered a key player modulating the efficacy of immune checkpoint inhibitor therapy. The study investigated the association between the response to anti-PD-1 therapy and the baseline gut microbiome in a Polish cohort of melanoma patients, alongside selected agents modifying the microbiome. Sixty-four melanoma patients enrolled for the anti-PD-1 therapy, and ten healthy subjects were recruited. The response to the treatment was assessed according to the response evaluation criteria in solid tumors, and patients were classified as responders or non-responders. The association between selected extrinsic factors and response was investigated using questionnaire-based analysis and the metataxonomics of the microbiota. In the responders, the Bacteroidota to Firmicutes ratio was higher, and the richness was decreased. The abundance of Prevotella copri and Bacteroides uniformis was related to the response, whereas the non-responders’ gut microbiota was enriched with Faecalibacterium prausnitzii and Desulfovibrio intestinalis and some unclassified Firmicutes. Dietary patterns, including plant, dairy, and fat consumption as well as gastrointestinal tract functioning were significantly associated with the therapeutic effects of the therapy. The specific gut microbiota along with diet were found to be associated with the response to the therapy in the population of melanoma patients.
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16
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Hone Lopez S, Jalving M, Fehrmann RS, Nagengast WB, de Vries EG, de Haan JJ. The gut wall’s potential as a partner for precision oncology in immune checkpoint treatment. Cancer Treat Rev 2022; 107:102406. [DOI: 10.1016/j.ctrv.2022.102406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 04/29/2022] [Accepted: 05/01/2022] [Indexed: 11/02/2022]
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17
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Guo X, Huang C, Xu J, Xu H, Liu L, Zhao H, Wang J, Huang W, Peng W, Chen Y, Nie Y, Zhou Y, Zhou Y. Gut Microbiota Is a Potential Biomarker in Inflammatory Bowel Disease. Front Nutr 2022; 8:818902. [PMID: 35127797 PMCID: PMC8814525 DOI: 10.3389/fnut.2021.818902] [Citation(s) in RCA: 71] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 12/29/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is characterized by relapse and remission alternately. It remains a great challenge to diagnose and assess disease activity during IBD due to the lack of specific markers. While traditional biomarkers from plasma and stool, such as C-reactive protein (CRP), fecal calprotectin (FC), and S100A12, can be used to measure inflammation, they are not specific to IBD and difficult to determine an effective cut-off value. There is consensus that gut microbiota is crucial for intestinal dysbiosis is closely associated with IBD etiopathology and pathogenesis. Multiple studies have documented differences in the composition of gut microbiota between patients with IBD and healthy individuals, particularly regarding microbial diversity and relative abundance of specific bacteria. Patients with IBD have higher levels of Proteobacteria and lower amounts of Bacteroides, Eubacterium, and Faecalibacterium than healthy individuals. This review summarizes the pros and cons of using traditional and microbiota biomarkers to assess disease severity and treatment outcomes and addresses the possibility of using microbiota-focused interventions during IBD treatment. Understanding the role of microbial biomarkers in the assessment of disease activity and treatment outcomes has the potential to change clinical practice and lead to the development of more personalized therapies.
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Affiliation(s)
- Xue Guo
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Chen Huang
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Jing Xu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Haoming Xu
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Le Liu
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Hailan Zhao
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Jiaqi Wang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Wenqi Huang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Wu Peng
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Ye Chen
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Yuqiang Nie
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Yongjian Zhou
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Youlian Zhou
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
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18
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Kowalski K, Mulak A. Small intestinal bacterial overgrowth in Alzheimer's disease. J Neural Transm (Vienna) 2021; 129:75-83. [PMID: 34797427 PMCID: PMC8738624 DOI: 10.1007/s00702-021-02440-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Accepted: 11/04/2021] [Indexed: 11/21/2022]
Abstract
The results of animal studies and clinical data support the gut microbiota contribution to the pathogenesis of Alzheimer’s disease (AD). The aim of this pilot study was to evaluate the prevalence of small intestinal bacterial overgrowth (SIBO) and fecal markers of intestinal inflammation and permeability in AD patients. The study was conducted in 45 AD patients and 27 controls. Data on comorbidities, pharmacotherapy, and gastrointestinal symptoms were acquired from medical records and a questionnaire. SIBO was evaluated using lactulose hydrogen breath test. Fecal calprotectin and zonulin levels were assessed by ELISA assays. The positive result of SIBO breath test was found in 49% of the AD patients and 22% of the controls (p = 0.025). The comparative analysis between SIBO-positive and SIBO-negative AD patients with respect to the degree of cognitive impairment, comorbidities and used medications did not reveal any statistically significant difference, except for less common heartburn in SIBO-positive AD patients than in SIBO-negative ones (9 vs 35%, p = 0.038). The median fecal calprotectin and zonulin levels in the AD group compared to the control group amounted to 43.1 vs 64.2 µg/g (p = 0.846) and 73.5 vs 49.0 ng/ml (p = 0.177), respectively. In the AD patients there was no association between the presence of SIBO and fecal calprotectin level. Patients with AD are characterized by higher prevalence of SIBO not associated with increased fecal calprotectin level that may be related to anti-inflammatory effect of cholinergic drugs used in the treatment of AD.
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Affiliation(s)
- Karol Kowalski
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556, Wrocław, Poland
| | - Agata Mulak
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556, Wrocław, Poland.
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19
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Kmeid M, Arker SH, Petchers A, Lukose G, Li H, Lee EC, Qualia CM, Arslan ME, Lee H. Appendiceal inflammation in colectomy is independently correlated with early pouchitis following ileal pouch anal anastomosis in ulcerative colitis and indeterminate colitis. Ann Diagn Pathol 2021; 55:151838. [PMID: 34626936 DOI: 10.1016/j.anndiagpath.2021.151838] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Revised: 09/23/2021] [Accepted: 09/28/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Appendiceal inflammation in colectomy is one of the histologic predictors of pouchitis in ulcerative colitis (UC) following ileal pouch anal anastomosis (IPAA). Fecal calprotectin level has been shown to increase 2 months prior to the onset of pouchitis. We evaluated whether inflammation and calprotectin expression in appendiceal specimens correlate with early-onset pouchitis in UC and indeterminate colitis (IC). MATERIALS AND METHODS IPAA (2000-2018) cases with appendix blocks available in colectomy specimens were identified (n = 93, 90 UC, 3 IC). Histologic features thought to predict pouchitis were evaluated. The degree of appendiceal inflammation was scored. Calprotectin immunostain was performed on the appendix blocks and the extent of mucosal staining was quantified. Electronic medical records were reviewed for demographics, smoking history, clinical pouchitis, time of onset of pouchitis, and clinical and endoscopic components of the Pouchitis Disease Activity Index (PDAI) score. Follow-up pouch biopsies were reviewed and scored to generate histologic PDAI score, when available. RESULTS Among the patients with clinical pouchitis (n = 73), moderate to severe appendiceal inflammation independently correlated with earlier pouchitis compared to no/mild inflammation (median time to pouchitis 12.0 vs. 23.8, log rank p = 0.016). Calprotectin staining correlated with inflammatory scores of the appendix (Spearman's rho, r = 0.630, p < 0.001) but not with early pouchitis (p > 0.05). CONCLUSIONS The presence of moderate to severe appendiceal inflammation at the time of colectomy was associated with a shorter time to pouchitis following IPAA. Calprotectin immunostain may be used to demonstrate the presence of inflammation in the appendix but its role in predicting early pouchitis remains limited.
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Affiliation(s)
- Michel Kmeid
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
| | - Soe Htet Arker
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
| | - Adam Petchers
- Department of Surgery, Albany Medical Center, Albany, NY, USA.
| | | | - Hua Li
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
| | - Edward C Lee
- Department of Surgery, Albany Medical Center, Albany, NY, USA.
| | - Cary M Qualia
- Department of Pediatrics, Albany Medical Center, Albany, NY, USA.
| | - Mustafa Erdem Arslan
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
| | - Hwajeong Lee
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
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20
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Chatziparasidis G, Kantar A. Calprotectin: An Ignored Biomarker of Neutrophilia in Pediatric Respiratory Diseases. CHILDREN-BASEL 2021; 8:children8060428. [PMID: 34063831 PMCID: PMC8223968 DOI: 10.3390/children8060428] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 05/18/2021] [Accepted: 05/19/2021] [Indexed: 12/20/2022]
Abstract
Calprotectin (CP) is a non-covalent heterodimer formed by the subunits S100A8 (A8) and S100A9 (A9). When neutrophils become activated, undergo disruption, or die, this abundant cytosolic neutrophil protein is released. By fervently chelating trace metal ions that are essential for bacterial development, CP plays an important role in human innate immunity. It also serves as an alarmin by controlling the inflammatory response after it is released. Extracellular concentrations of CP increase in response to infection and inflammation, and are used as a biomarker of neutrophil activation in a variety of inflammatory diseases. Although it has been almost 40 years since CP was discovered, its use in daily pediatric practice is still limited. Current evidence suggests that CP could be used as a biomarker in a variety of pediatric respiratory diseases, and could become a valuable key factor in promoting diagnostic and therapeutic capacity. The aim of this study is to re-introduce CP to the medical community and to emphasize its potential role with the hope of integrating it as a useful adjunct, in the practice of pediatric respiratory medicine.
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Affiliation(s)
| | - Ahmad Kantar
- Pediatric Asthma and Cough Centre, Instituti Ospedalieri Bergamaschi, University and Research Hospitals, 24046 Bergamo, Italy
- Correspondence:
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21
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D'Amico F, Rubin DT, Kotze PG, Magro F, Siegmund B, Kobayashi T, Olivera PA, Bossuyt P, Pouillon L, Louis E, Domènech E, Ghosh S, Danese S, Peyrin‐Biroulet L. International consensus on methodological issues in standardization of fecal calprotectin measurement in inflammatory bowel diseases. United European Gastroenterol J 2021; 9:451-460. [PMID: 33961734 PMCID: PMC8259254 DOI: 10.1002/ueg2.12069] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 02/26/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Fecal calprotectin (FC) is a non-invasive marker of gut inflammation which is frequently used to guide therapeutic decisions in patients with inflammatory bowel diseases (IBD). Each step of FC measurement can influence the results, leading to misinterpretations and potentially impacting the management of IBD patients. To date, there is high heterogeneity between FC measurements and no current method is universally accepted as a standard. AIMS Our aim was to provide clear position statementsabout the pre-analytical and the analytical phases of FC measurement to homogenize FC levels and to minimize variability and risk of misinterpretation through aninternational consensus. MATERIALS & METHODS Fourteen physicians with expertise in the field of IBD and FC from 11 countries attended a virtual international consensus meeting on July 17th, 2020. A systematic literature was conducted and the literature evidence was shared and discussedamong the participants. Statements were formulated, discussed, and voted. Statements were considered approved if all participants agreed. RESULTS Nine statements were formulated and approved. Based on the available evidence, quantitative tests should be preferred for measuring FC. Furthermore, FC measurement, if possible, should always be performed with the same method and factors influencing FC levels should be taken into account when interpreting the results. DISCUSSION FC has an increasingly important role in the management of patients with IBD. However, large multicenter studies should be conducted to define the reproducibility and to confirm the diagnostic accuracy of the available FC tests. CONCLUSION FC concentrations guide clinicians' treatment decisions. Our statements have a relevant impact in daily practice and could be applied in clinical trials to standardize FC measurement.
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Affiliation(s)
- Ferdinando D'Amico
- Department of Biomedical SciencesHumanitas UniversityMilanItaly
- Department of Gastroenterology and Inserm U1256Nutrition – Genetics and Exposure to Environmental RisksUniversity Hospital of NancyUniversity of LorraineVandoeuvre‐lès‐NancyFrance
| | - David T. Rubin
- Section of Gastroenterology, Hepatology and NutritionUniversity of Chicago Department of MedicineChicagoIllinoisUSA
| | | | - Fernando Magro
- Department of GastroenterologyCentro Hospitalar São JoãoPortoPortugal
| | - Britta Siegmund
- Medizinische Klinik m. S. Gastroenterologie, Infektiologie und RheumatologieCharité ‐ Universitätsmedizin BerlinCorporate Member of Freie Universität BerlinHumboldt‐Universität zu Berlinand Berlin Institute of HealthBerlinGermany
| | - Taku Kobayashi
- Center for Advanced IBD Research and TreatmentKitasato University Kitasato Institute HospitalTokyoJapan
| | - Pablo A. Olivera
- Gastroenterology SectionDepartment of Internal MedicineCentro de Educación Médica e Investigaciones Clínicas (CEMIC)Buenos AiresArgentina
| | - Peter Bossuyt
- Imelda GI Clinical Research CenterImelda General HospitalBonheidenBelgium
| | - Lieven Pouillon
- Imelda GI Clinical Research CenterImelda General HospitalBonheidenBelgium
| | - Edouard Louis
- Department of GastroenterologyCHU Liège University HospitalLiègeBelgium
| | - Eugeni Domènech
- Gastroenterology DepartmentHospital Universitari Germans Trias i PujolBadalonaCataloniaSpain
- Departament de MedicinaUniversitat Autònoma de BarcelonaBarcelonaSpain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)MadridSpain
| | - Subrata Ghosh
- NIHR Biomedical Research CentreUniversity of Birmingham and University Hospitals NHS Foundation TrustBirminghamUK
| | - Silvio Danese
- Department of Biomedical SciencesHumanitas UniversityMilanItaly
- IBD CenterHumanitas Research HospitalIRCCSMilanItaly
| | - Laurent Peyrin‐Biroulet
- Department of Gastroenterology and Inserm U1256Nutrition – Genetics and Exposure to Environmental RisksUniversity Hospital of NancyUniversity of LorraineVandoeuvre‐lès‐NancyFrance
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22
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The utility of faecal and urine biomarkers for small bowel diseases. Curr Opin Gastroenterol 2021; 37:284-294. [PMID: 33769381 DOI: 10.1097/mog.0000000000000730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
PURPOSE OF REVIEW Small bowel diseases pose a unique diagnostic and management challenge and often requires tertiary specialist referral. The use of biomarkers may provide a cheap, noninvasive tool to assess the small bowel in terms of diagnosis, offering a better way to triage referrals and select patients for early management. This review looks at the most recent evidence behind the use of several faecal and urine biomarkers for small bowel diseases. RECENT FINDINGS Faecal calprotectin shows the most promise, with evidence to support its role in predicting relapse postsurgery and monitoring treatment response in patients with Crohn's disease. A faecal calprotectin less than 50 μg/g may also be used as a cut-off to triage further investigation. Faecal lactoferrin also appears promising as a marker of small bowel inflammation. A positive faecal immunohistochemistry test precapsule may help to prioritize referrals for obscure bleeding. SUMMARY The use of biomarkers in the diagnosis and management of small bowel disease is still controversial and remains unclear. More studies are required to further develop their potential and before societal guidelines can be developed to direct their appropriate use in clinical practice.
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23
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The Use of Fecal Calprotectin Testing in Paediatric Disorders: A Position Paper of the European Society for Paediatric Gastroenterology and Nutrition Gastroenterology Committee. J Pediatr Gastroenterol Nutr 2021; 72:617-640. [PMID: 33716293 DOI: 10.1097/mpg.0000000000003046] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES The aim of the study was to review the evidence regarding the clinical use and value of fecal calprotectin (FC) measurements in different gastrointestinal disorders in children. METHODS A literature search was conducted in the PubMed, MEDLINE, EMBASE, and Cochrane databases until October 31, 2019. Subtopics were identified and each assigned to individual authors. RESULTS A total of 28 recommendations were voted on using the nominal voting technique. Recommendations are given related to sampling, measurement methods, and results interpretation. The 14 authors anonymously voted on each recommendation using a 9-point scale (1 strongly disagree to 9 fully agree). Consensus was considered achieved if at least 75% of the authors voted 6, 7, 8, or 9. CONCLUSIONS Consensus was reached for all recommendations. Limitations for the use of FC in clinical practice include variability in extraction methodology, performance of test kits as well as the need to establish local reference ranges because of the influence of individual factors, such as age, diet, microbiota, and drugs. The main utility of FC measurement at present is in the diagnosis and monitoring of inflammatory bowel disease (IBD) as well as to differentiate it from functional gastrointestinal disorders (FAPDs). FC, however, has neither utility in the diagnosis of infantile colic nor to differentiate between functional and organic constipation. A rise in FC concentration, may alert to the risk of developing necrotizing enterocolitis and help identifying gastrointestinal involvement in children with Henoch-Schönlein purpura. FC measurement is of little value in Cow's Milk Protein Allergy, coeliac disease (CD), and cystic fibrosis. FC does neither help to distinguish bacterial from viral acute gastroenteritis (AGE), nor to diagnose Helicobacter Pylori infection, small intestinal bacterial overgrowth (SIBO), acute appendicitis (AA), or intestinal polyps.
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24
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Heilmann RM, Guard MM, Toresson L, Unterer S, Grellet A, Grützner N, Suchodolski JS, Steiner JM. Association of clinical characteristics and lifestyle factors with fecal S100/calgranulin concentrations in healthy dogs. Vet Med Sci 2021; 7:1131-1143. [PMID: 33751838 PMCID: PMC8294382 DOI: 10.1002/vms3.469] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 02/10/2021] [Accepted: 02/22/2021] [Indexed: 02/06/2023] Open
Abstract
Background Fecal S100/calgranulin (S100A12 and calprotectin) concentrations are useful markers of gastrointestinal inflammation in dogs. In people, fecal S100/calgranulin concentrations are affected by age, obesity, diet and other lifestyle factors. Knowledge about the effects of such factors on fecal S100/calgranulin concentrations in dogs is currently scarce. Objective To evaluate the association between several factors and fecal S100/calgranulin concentrations in a large cohort of healthy adult dogs. Methods Single‐spot fecal samples from 181 healthy pet dogs and data derived from a standard questionnaire served to evaluate the effect of age, sex, reproductive status, body weight and body condition, breed type and size, vaccination, endoparasite treatment, diet, environment and travel history on fecal S100/calgranulin concentrations and the fecal calgranulin ratio (fCalR). Results Univariate analysis showed a significant association of reproductive status (in female dogs) and breed size with fecal S100A12, fecal calprotectin and fCalR. Breed type was linked to fecal S100A12 concentrations and fCalR; recent vaccination (particularly with a vaccine against canine parvovirus) to fCalR. In multivariate models, breed size was linked to fecal S100A12 and calprotectin concentrations, and recent vaccination affected S100A12 concentrations. Conclusions Breed size, recent vaccination and reproductive status in female dogs can affect fecal S100/calgranulin concentrations, and these biomarkers should be interpreted in light of those confounding factors. The utility of reference intervals for fecal canine S100/calgranulin concentrations might be improved through stratification by sex/reproductive status and breed size. Fecal canine S100/calgranulin concentrations are not confounded by age, body condition, deworming, diet, environment or travel history.
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Affiliation(s)
- Romy M Heilmann
- Department for Small Animals, Veterinary Teaching Hospital, College of Veterinary Medicine, University of Leipzig, Leipzig, Germany.,School of Veterinary Science, Massey University, Palmerston North, New Zealand
| | - Melissa M Guard
- Gastrointestinal Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA
| | - Linda Toresson
- Evidensia Specialist Animal Hospital, Helsingborg, Sweden.,Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, Helsinki University, Helsinki, Finland
| | - Stefan Unterer
- Clinic of Small Animal Internal Medicine, Center for Clinical Veterinary Medicine, Ludwig-Maximilians-University, Munich, Germany
| | - Aurélien Grellet
- NeoCare, UMR INRA/ENVT 1225 IHAP, Reproduction, Université de Toulouse, Toulouse, France
| | - Niels Grützner
- School of Veterinary Science, Massey University, Palmerston North, New Zealand.,Clinic for Swine and Small Ruminants, Forensic Medicine and Ambulatory Service, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Jan S Suchodolski
- Gastrointestinal Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA
| | - Joerg M Steiner
- Gastrointestinal Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA
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25
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The Multiomics Analyses of Fecal Matrix and Its Significance to Coeliac Disease Gut Profiling. Int J Mol Sci 2021; 22:ijms22041965. [PMID: 33671197 PMCID: PMC7922330 DOI: 10.3390/ijms22041965] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 02/08/2021] [Accepted: 02/11/2021] [Indexed: 12/15/2022] Open
Abstract
Gastrointestinal (GIT) diseases have risen globally in recent years, and early detection of the host’s gut microbiota, typically through fecal material, has become a crucial component for rapid diagnosis of such diseases. Human fecal material is a complex substance composed of undigested macromolecules and particles, and the processing of such matter is a challenge due to the unstable nature of its products and the complexity of the matrix. The identification of these products can be used as an indication for present and future diseases; however, many researchers focus on one variable or marker looking for specific biomarkers of disease. Therefore, the combination of genomics, transcriptomics, proteomics and metabonomics can give a detailed and complete insight into the gut environment. The proper sample collection, sample preparation and accurate analytical methods play a crucial role in generating precise microbial data and hypotheses in gut microbiome research, as well as multivariate data analysis in determining the gut microbiome functionality in regard to diseases. This review summarizes fecal sample protocols involved in profiling coeliac disease.
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26
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Kotsiou OS, Papagiannis D, Papadopoulou R, Gourgoulianis KI. Calprotectin in Lung Diseases. Int J Mol Sci 2021; 22:ijms22041706. [PMID: 33567747 PMCID: PMC7915440 DOI: 10.3390/ijms22041706] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 01/31/2021] [Accepted: 02/04/2021] [Indexed: 12/14/2022] Open
Abstract
Calprotectin (CLP) is a heterodimer formed by two S-100 calcium-binding cytosolic proteins, S100A8 and S100A9. It is a multifunctional protein expressed mainly by neutrophils and released extracellularly by activated or damaged cells mediating a broad range of physiological and pathological responses. It has been more than 20 years since the implication of S100A8/A9 in the inflammatory process was shown; however, the evaluation of its role in the pathogenesis of respiratory diseases or its usefulness as a biomarker for the appropriate diagnosis and prognosis of lung diseases have only gained attention in recent years. This review aimed to provide current knowledge regarding the potential role of CLP in the pathophysiology of lung diseases and describe how this knowledge is, up until now, translated into daily clinical practice. CLP is involved in numerous cellular processes in lung health and disease. In addition to its anti-microbial functions, CLP also serves as a molecule with pro- and anti-tumor properties related to cell survival and growth, angiogenesis, DNA damage response, and the remodeling of the extracellular matrix. The findings of this review potentially introduce CLP in daily clinical practice within the spectrum of respiratory diseases.
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Affiliation(s)
- Ourania S. Kotsiou
- Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece;
- Department of Nursing, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece;
- Correspondence:
| | - Dimitrios Papagiannis
- Department of Nursing, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece;
| | - Rodanthi Papadopoulou
- Human Nutrition, School of Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow G31 2ER, UK;
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27
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Patel C, Keller L, Welsche S, Hattendorf J, Sayasone S, Ali SM, Ame SM, Coulibaly JT, Hürlimann E, Keiser J. Assessment of fecal calprotectin and fecal occult blood as point-of-care markers for soil-transmitted helminth attributable intestinal morbidity in a case-control substudy conducted in Côte d'Ivoire, Lao PDR and Pemba Island, Tanzania. EClinicalMedicine 2021; 32:100724. [PMID: 33554091 PMCID: PMC7851339 DOI: 10.1016/j.eclinm.2021.100724] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 01/06/2021] [Accepted: 01/07/2021] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND Infections with soil-transmitted helminths (STHs) may result in chronic inflammatory disorders affecting the human host. The objective of this study was to evaluate Fecal Calprotectin (FC) and Fecal Occult Blood (FOB) in individuals infected and non-infected with STHs to identify potential intestinal morbidity markers. METHODS Stool from participants diagnosed positive for Trichuris trichiura and concomitant STH infections from three countries was used to perform FC and FOB point-of-care assays. Simultaneously, identified STH negative participants underwent FC and FOB testing as controls. Potential associations between test results and determinants were analyzed using multivariable logistic regression. FINDINGS In total, 1034 T. trichiura infected cases (mostly light infections) and 157 STH negative controls were tested for FC and FOB. Among all participants tested, 18·5% had ≥ 50 µg/g FC concentration, while 14 (1·2%) were positive for FOB. No statistically significant association was found between T. trichiura infection or Ascaris lumbricoides co-infection and FC concentration, while an inverse association (odds ratio (OR): 0·45, 95% credible intervals (CrI): 0·26, 0·75) was found between hookworm co-infection and FC concentration. In Lao PDR, the proportion of participants in the ≥ 50 µg/g FC category was significantly higher in the oldest age category compared to the 5-11 years group (OR: 3·31, 95% CrI: 1·62, 7·24). Too few participants were found positive for FOB to derive any conclusions. INTERPRETATION Studies are needed to better understand the relationship between intestinal morbidity and STH infections. Suitable, standardized, low-cost markers of STH attributable morbidity to better monitor the impact of STH control interventions are necessary. FUNDING BMGF (OPP1153928).
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Affiliation(s)
- Chandni Patel
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Ladina Keller
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Sophie Welsche
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Jan Hattendorf
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Somphou Sayasone
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
- Department of International Program for Health in the Tropics, Lao Tropical and Public Health Institute, Vientiane, Lao People's Democratic Republic
| | - Said M. Ali
- Public Health Laboratory Ivo de Carneri, Chake Chake, Pemba, Zanzibar, Tanzania
| | - Shaali M. Ame
- Public Health Laboratory Ivo de Carneri, Chake Chake, Pemba, Zanzibar, Tanzania
| | - Jean Tenena Coulibaly
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
- Unité de Formation et de Recherche Biosciences, Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire
- Department of Research and Development, Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, Abidjan, Côte d'Ivoire
| | - Eveline Hürlimann
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Jennifer Keiser
- Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
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28
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D'Amico F, Nancey S, Danese S, Peyrin-Biroulet L. A Practical Guide for Faecal Calprotectin Measurement: Myths and Realities. J Crohns Colitis 2021; 15:152-161. [PMID: 32392336 DOI: 10.1093/ecco-jcc/jjaa093] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Faecal calprotectin [FC] is a valid and non-invasive marker of mucosal inflammation. It is widely used both in clinical trials and in daily clinical practice for patients with inflammatory bowel diseases, but currently no accepted standardization for FC testing is available. Our primary aim here was to provide a clinician's guide containing all the practical information on FC measurement in order to avoid any confounding factors, to minimize intra- and inter-individual variability in dosage, and to ensure a better and adequate interpretation of the results. METHODS We conducted a detailed search of the scientific literature in the PubMed/MEDLINE, EMBASE and Cochrane databases up to January 2020 to find all relevant and available articles on pre-analytical and analytical phases of FC measurement. RESULTS FC testing is a multi-step procedure consisting of a pre-analytical phase aimed to collect and process the stool sample and a subsequent analytical phase of FC measurement. Several factors can influence test results determining false positives or false negatives. Importantly, this faecal marker is mostly used for patient follow-up and as a predictor of treatment response. For this reason, any altered data may affect the physicians' decisions, negatively impacting on patient management. CONCLUSIONS This review provides for the first time practical advice to minimize dosage variability, although further dedicated studies are needed to compare commercially available tests and identify the best tools for the most precise and accurate FC measurement.
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Affiliation(s)
- Ferdinando D'Amico
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Stéphane Nancey
- Department of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre Benite, and Inserm U1111, CIRI, Lyon, France
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,IBD Center, Department of Gastroenterology, Humanitas Research Hospital, Rozzano -IRCCS-, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
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29
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Sjöström B, Bredberg A, Mandl T, Alonso-Magdalena L, Ohlsson B, Lavasani S, Nouri M, Henriksson G. Increased intestinal permeability in primary Sjögren's syndrome and multiple sclerosis. J Transl Autoimmun 2021; 4:100082. [PMID: 33506194 PMCID: PMC7815467 DOI: 10.1016/j.jtauto.2021.100082] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 12/23/2020] [Accepted: 12/30/2020] [Indexed: 02/07/2023] Open
Abstract
There is increasing evidence suggesting a role of intestinal dysfunction in a number of autoimmune diseases. Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease with a documented increased level of intestinal inflammation, whereas multiple sclerosis (MS) is an organ-specific autoimmune disease known to exhibit increased intestinal permeability. In this study we determine to what extent intestinal inflammation, analysed by a faecal calprotectin ELISA, is accompanied by altered intestinal wall permeability, as measured by a lactulose and mannitol intestinal absorption assay. Intestinal permeability was increased in both pSS and MS patients, while faecal calprotectin was elevated in pSS but normal in MS. Our findings suggest different mechanisms mediating a leaky gut in these two diseases: in pSS there is autoimmune attack directly on the intestinal wall; in MS, with autoimmunity being limited to the CNS, it may be due to a disturbed CNS regulation of enteric nerve function.
Intestinal permeability analysed by sugar absorption is increased in primary Sjögren’s syndrome and multiple sclerosis. Intestinal wall inflammation as determined by faecal calprotectin is observed in pSS but not in MS. Leaky gut may be due to autoimmune targeting of the intestinal wall in pSS and to disturbed intestinal innervation in MS.
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Affiliation(s)
- Bitte Sjöström
- Department of Laboratory Medicine, Medical Microbiology, Lund University, Lund, Sweden
| | - Anders Bredberg
- Department of Laboratory Medicine, Medical Microbiology, Lund University, Lund, Sweden
| | - Thomas Mandl
- Department of Rheumatology, Skåne University Hospital, Malmö, Lund University, Lund, Sweden.,Department of Clinical Sciences, Malmö, Rheumatology, Lund University, Malmö, Sweden
| | - Lucía Alonso-Magdalena
- Department of Neurology, Skåne University Hospital, Malmö/Lund, Lund University, Sweden.,Department of Clinical Sciences, Malmö, Neurology, Lund University, Sweden
| | - Bodil Ohlsson
- Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden.,Department of Clinical Sciences, Malmö, Lund University, Sweden
| | - Shahram Lavasani
- Department of Biology, Lund University, Lund, Sweden.,ImmuneBiotech AB, Medicon Village, Lund, Sweden
| | - Mehrnaz Nouri
- Department of Biology, Lund University, Lund, Sweden.,Department of Clinical Sciences, Clinical Research Centre, Surgery Research Unit, Lund University, Malmö, Sweden
| | - Gunnel Henriksson
- Department of Laboratory Medicine, Medical Microbiology, Lund University, Lund, Sweden.,Department of Clinical Microbiology, Skåne University Hospital, Lund, Sweden
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30
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Roca M, Rodriguez Varela A, Carvajal E, Donat E, Cano F, Armisen A, Vaya MJ, Ekoff H, Hervas D, Rydell N, Ribes-Koninckx C. Fecal calprotectin in healthy children aged 4-16 years. Sci Rep 2020; 10:20565. [PMID: 33239728 PMCID: PMC7688634 DOI: 10.1038/s41598-020-77625-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 11/12/2020] [Indexed: 12/13/2022] Open
Abstract
Reference values of fecal calprotectin (fCP) have not been convincingly established in children. We aimed to investigate fCP concentrations in a larger population of healthy children aged 4–16 years to analyze more in depth the behavior of fCP in this age range and to determine if cut-off levels could be conclusively recommended. A prospective study was conducted to investigate fCP concentrations of healthy children aged 4–16 years. In 212 healthy children, the median and 95th percentile for fCP were 18.8 mg/kg and 104.5 mg/kg, respectively. We found a statistically significant association between the 95th percentile of fCP concentrations and age (p < 0.001). We propose a nomogram to facilitate the interpretation of fCP results in children aged 4–16 years. Further studies are required to validate the proposed values in clinical practice.
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Affiliation(s)
- María Roca
- Celiac Disease and Digestive Immunopathology Unit, Instituto de Investigación Sanitaria La Fe, P.O. Box 46026, Valencia, Spain.
| | | | - Eva Carvajal
- Department of Paediatrics, Hospital Casa de Salud, P.O. Box 46021, Valencia, Spain
| | - Ester Donat
- Celiac Disease and Digestive Immunopathology Unit, Instituto de Investigación Sanitaria La Fe, P.O. Box 46026, Valencia, Spain.,Pediatric Gastrohepatology Unit, Hospital Universitario y Politécnico La Fe, P.O. Box 46026, Valencia, Spain
| | - Francisco Cano
- Primary Health Care Center of Betera, P.O. Box 46117, Bétera, Valencia, Spain
| | - Ana Armisen
- Primary Health Care Center of Betera, P.O. Box 46117, Bétera, Valencia, Spain
| | - Maria Jose Vaya
- Primary Health Care Center of Betera, P.O. Box 46117, Bétera, Valencia, Spain
| | - Helena Ekoff
- Thermo Fisher Scientific, PO Box 6460, Uppsala, Sweden
| | - David Hervas
- Biostatistics Unit, Instituto de Investigación Sanitaria La Fe, P.O. Box 46026, Valencia, Spain
| | - Niclas Rydell
- Thermo Fisher Scientific, PO Box 6460, Uppsala, Sweden
| | - Carmen Ribes-Koninckx
- Celiac Disease and Digestive Immunopathology Unit, Instituto de Investigación Sanitaria La Fe, P.O. Box 46026, Valencia, Spain.,Pediatric Gastrohepatology Unit, Hospital Universitario y Politécnico La Fe, P.O. Box 46026, Valencia, Spain
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31
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Khaki-Khatibi F, Qujeq D, Kashifard M, Moein S, Maniati M, Vaghari-Tabari M. Calprotectin in inflammatory bowel disease. Clin Chim Acta 2020; 510:556-565. [PMID: 32818491 PMCID: PMC7431395 DOI: 10.1016/j.cca.2020.08.025] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 08/11/2020] [Accepted: 08/13/2020] [Indexed: 02/07/2023]
Abstract
The term IBD is usually used for referring to a group of inflammatory gastro-intestinal diseases (mainly Crohn's disease and ulcerative colitis). Accordingly, IBD arises as a result of inappropriate immune response to intestinal commensal organisms among genetically susceptible individuals. Performing colonoscopy and histopathologic evaluation on an inflamed bowel biopsy specimen are currently considered as gold standards for diagnosis and management of IBD. Correspondingly, these techniques are known to be invasive and costly. In recent decades, fecal calprotectin, as a biomarker, has received much attention for the diagnosis and non-invasive management of IBD. Up to now, many studies have investigated the efficacy of fecal calprotectin in the areas of IBD differentiation from IBS, prediction of endoscopic and histologic activities of IBD and prediction of disease recurrence. Although some of these studies have reported promising results, some others have shown significant limitations. Therefore, in this paper, we reviewed the most interesting ones of these studies after a brief discussion of the laboratory measurement of fecal calprotectin. Moreover, we attempted to provide an answer for the question of whether fecal-calprotectin could be considered as a potential surrogate marker for colonoscopy.
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Affiliation(s)
- Fatemeh Khaki-Khatibi
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Durdi Qujeq
- Cellular and Molecular Biology Research Center (CMBRC), Health Research Institute, Babol University of Medical Sciences, Babol, Iran,Department of Clinical Biochemistry, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Mehrdad Kashifard
- Department of Internal Medicine, Gastroenterology Division, Ayatollah Rouhani Hospital, Babol University of Medical Sciences, Babol, Iran
| | - Soheila Moein
- Department of Biochemistry, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Mahmood Maniati
- English Department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mostafa Vaghari-Tabari
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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Ebrahimi B, Nazarinia M, Molayem M. Calprotectin, an available prognostic biomarker in systemic sclerosis: a systematic review. Clin Rheumatol 2020; 40:1709-1715. [PMID: 33044726 DOI: 10.1007/s10067-020-05446-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 10/01/2020] [Accepted: 10/05/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND Finding easier and less invasive biologic biomarker in the clinical specimen of systemic sclerosis (SSc) patients can be effective in diagnosing and treating SSc-associated multisystem diseases. The complex of S100A8 and S100A9 (Calprotectin) is an easily available prognostic biomarker that secretes from immune cells and is necessary for initiating the immune response to noninfectious inflammation processes. The present study aims to evaluate the effectiveness of Calprotectin in specimen of SSc patients. We reviewed the evidence for Calprotectin in diagnostic and prognostic of SSc patients. METHODS This systematic review was done to identify studies on "Calprotectin" within "SSc" patients. PubMed, Web of knowledge, and Scopus were searched for this purpose. A standardized form was used to extract diseases, sample size, biomarkers identified, source of biomarker, and its effects. RESULTS Overall, the 16 articles selected show that the main sources of Calprotectin were plasma, bronchoalveolar lavage fluid, and especially stool. CONCLUSION The best source of Calprotectin was fecal Calprotectin that could show the inflammation and small intestinal bacterial overgrowth (SIBO) on SSc patients. Also, the most arguable source is plasma because of its low sample size. Comparing the Calprotectin level in different rheumatic diseases showed the specificity of fecal Calprotectin for SSc disease. Nevertheless, it has to be noted that Calprotectin correlates with some other factors such as age, PIP drug, and nonsteroidal anti-inflammatory drugs.
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Affiliation(s)
- Bahareh Ebrahimi
- Shiraz Geriatric Research Center, Shiraz University of Medical Sciences, Shiraz, 71936-35899, Iran
| | - MohamadAli Nazarinia
- Shiraz Geriatric Research Center, Shiraz University of Medical Sciences, Shiraz, 71936-35899, Iran.
- Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Mina Molayem
- Shiraz Geriatric Research Center, Shiraz University of Medical Sciences, Shiraz, 71936-35899, Iran
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Mennini M, Fiocchi AG, Cafarotti A, Montesano M, Mauro A, Villa MP, Di Nardo G. Food protein-induced allergic proctocolitis in infants: Literature review and proposal of a management protocol. World Allergy Organ J 2020; 13:100471. [PMID: 33072241 PMCID: PMC7549143 DOI: 10.1016/j.waojou.2020.100471] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 09/12/2020] [Accepted: 09/14/2020] [Indexed: 02/06/2023] Open
Abstract
Food protein-induced allergic proctocolitis (FPIAP) is a condition characterized by inflammatory changes in the distal colon in response to one or more foreign food proteins because of immune-mediated reactions. FPIAP prevalence estimates range widely from 0.16% in healthy children and 64% in patients with blood in stools. In clinical practice, FPIAP is diagnosed when patients respond positively to the elimination of a suspected triggering food allergen. Nevertheless, significant proportions of infants get misdiagnosed with IgE mediated allergy and undergo unnecessary dietary changes. Diagnosis is based on clinical symptoms, a good response to an allergen-free diet and the recurrence of symptoms during the "allergy challenge test". Sometimes clinical features may be non-specific and the etiology of rectal bleeding in childhood may be heterogeneous. Therefore, it is crucial to exclude a variety of other possible causes of rectal bleeding in the pediatric age group, including infection, anal fissure, intestinal intussusception and, in infants, necrotizing enterocolitis and very early onset inflammatory bowel disease. The diagnostic workup includes in those cases invasive procedures such as sigmoidoscopy and colonoscopy with biopsies. The high prevalence of FPIAP contrasts with the lack of known information about the pathogenesis of this condition. For this reason and due to the absence of a review of the evidence, a literature review appears necessary to clarify some aspects of allergic colitis. The aim of the review is to fill this gap and to lay the foundations for a subsequent evidence-based approach to the condition.
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Affiliation(s)
- Maurizio Mennini
- Multifactorial and Systemic Diseases Research Area, Predictive and Preventive Medicine Research Unit, Division of Allergy Bambino Gesù Children's Hospital IRCCS, Rome, Italy
| | - Alessandro Giovanni Fiocchi
- Multifactorial and Systemic Diseases Research Area, Predictive and Preventive Medicine Research Unit, Division of Allergy Bambino Gesù Children's Hospital IRCCS, Rome, Italy
| | - Arianna Cafarotti
- Multifactorial and Systemic Diseases Research Area, Predictive and Preventive Medicine Research Unit, Division of Allergy Bambino Gesù Children's Hospital IRCCS, Rome, Italy
| | - Marilisa Montesano
- Chair of Pediatrics, NESMOS Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Sant’Andrea University Hospital, Rome, Italy
| | - Angela Mauro
- Department of Paediatrics, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - Maria Pia Villa
- Chair of Pediatrics, NESMOS Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Sant’Andrea University Hospital, Rome, Italy
| | - Giovanni Di Nardo
- Chair of Pediatrics, NESMOS Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Sant’Andrea University Hospital, Rome, Italy
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Park SY. Age-Related Fecal Calprotectin Concentrations in Healthy Adults. KOREAN JOURNAL OF CLINICAL LABORATORY SCIENCE 2020. [DOI: 10.15324/kjcls.2020.52.3.181] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Shin Young Park
- Department of Clinical Laboratory Science, Cheju Halla University, Jeju, Korea
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Abstract
OBJECTIVES Fecal calprotectin is a valued surrogate marker for intestinal inflammation. It has been argued that calprotectin levels are higher in early age than in later life hampering the use of calprotectin in young children. SUBJECTS AND METHODS To study age-related variation, we used data from our laboratory information system on consecutive, unselected fecal calprotectin measurements from 2014 to 2017 in all children aged 0 to 18 years. From each individual, the first measurement was included and repeated measurements were excluded. Fecal calprotectin was quantitated in the major clinical laboratory in southern Finland, HUSLAB with an ELISA kit from Calpro AS (Calpro/Calprolab, Oslo, Norway). Currently, the assay is performed on two automatic pipetting analysers (Dynex DS2, Chantilly, USA) according to the instructions of the manufacturer. RESULTS There were altogether 11,255 fecal calprotectin results from as many children. The median level of fecal calprotectin was 51 mg/kg in infants < 1 year of age (95th percentile 648 mg/kg; n = 239). This was 3-4-fold higher when compared to yearly age groups from 1 to 10 years (total number of children included 5,691). Across yearly age groups from 11 to 18, the median values varied from 11 to 19 mg/kg (total number of included children 5,325). The proportion of samples above the routine cut-off for an elevated concentration >100 mg/kg increased with increasing age. CONCLUSIONS Fecal calprotectin values in children beyond the first year of life are in general low and comparable in children and adolescents.
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Affiliation(s)
- Kaija-Leena Kolho
- Children´s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Henrik Alfthan
- Helsinki University Hospital Laboratory (HUSLAB), Helsinki University Hospital, Helsinki, Finland
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Laserna-Mendieta EJ, Lucendo AJ. Faecal calprotectin in inflammatory bowel diseases: a review focused on meta-analyses and routine usage limitations. Clin Chem Lab Med 2020; 57:1295-1307. [PMID: 30785706 DOI: 10.1515/cclm-2018-1063] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Accepted: 11/28/2018] [Indexed: 12/12/2022]
Abstract
A growing body of evidence has been published about the usefulness of measuring calprotectin in faecal samples (FCAL) in inflammatory bowel disease (IBD) assessment, including diagnosis, monitoring of disease activity and relapse prediction. Several systematic reviews with meta-analyses compiling studies for each particular clinical setting have been carried out in recent years. Most of these were focused on the use of FCAL in IBD diagnosis and showed a relevant role for this marker in selecting patients with gastrointestinal symptoms who would not need a further examination by endoscopy. Although a lesser number of meta-analyses have been performed on the use of FCAL as a surrogate marker of disease activity, a close correlation between FCAL and endoscopic activity of IBD has been shown. With respect to the predictive capacity of FCAL for IBD relapse, a single meta-analysis published indicates that this role is more limited. Furthermore, FCAL thresholds vary considerably depending on the clinical setting and, what is more concerning, among different commercially available assays due to a lack of FCAL concentration interchangeability. Here, we summarise recent publications about the role and limitations of FCAL in IBD, with a special focus on meta-analyses, and give an overview of alternative faecal biomarkers.
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Affiliation(s)
- Emilio J Laserna-Mendieta
- Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain.,Clinical Laboratory, Hospital General de Villarrobledo, Villarrobledo, Spain
| | - Alfredo J Lucendo
- Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain.,Biomedical Research Network Centre for Liver and Digestive Diseases (CIBEREHD), Madrid, Spain
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Cremer A, Ku J, Amininejad L, Bouvry MR, Brohet F, Liefferinckx C, Devière J, van Gossum A, Smet J, Stordeur P, Franchimont D. Variability of Faecal Calprotectin in Inflammatory Bowel Disease Patients: An Observational Case-control Study. J Crohns Colitis 2019; 13:1372-1379. [PMID: 30944925 DOI: 10.1093/ecco-jcc/jjz069] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Several factors have been reported to affect faecal calprotectin [FC] values, and significant variation in FC concentrations has been observed in inflammatory bowel disease [IBD] patients. We aimed to evaluate FC variability in IBD patients, and to assess the robustness of a single stool punch. METHODS This is a single-centre observational case-control study. Disease activity was assessed using endoscopic and clinical activity scores, as well as C-reactive protein levels. Stool samples were collected twice within a 1 to 6 days interval, and FC was measured on punches and homogenates by fluorometric enzyme immunocapture assay. RESULTS In all, 260 stool samples were collected from 120 patients. Intrastool variability was low, with an intraclass correlation coefficient for single measures between three punches from a single stool sample of 0.91, and median coefficient of variation [CV] of 17%. CV of two stool samples a few days apart [intra-individual variability] were significantly higher [p <0.01] with median CV of 36%. FC standard deviations correlated with mean FC levels either for intrastool or for intra-individual variability, with a Spearman's coefficient of rank correlation of 0.85 and 0.78, respectively [p <0.01]. Disease type, location, activity, and FC levels did not influence variability. CONCLUSIONS A single stool punch is reliable for FC measurement, considering that intrastool variability is low. Intra-individual variability a few days apart is significantly higher. Therefore, decision-making strategies based on single measurements should consider this variability, to determine the minimum optimal variation to be achieved, rather than a cut-off, especially in high FC levels.
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Affiliation(s)
- Anneline Cremer
- Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.,Department of Gastroenterology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Jade Ku
- Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
| | - Leila Amininejad
- Department of Gastroenterology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Marie-Rose Bouvry
- Immunobiology Clinic, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Fabian Brohet
- Immunobiology Clinic, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Claire Liefferinckx
- Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
| | - Jacques Devière
- Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.,Department of Gastroenterology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - André van Gossum
- Department of Gastroenterology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Julie Smet
- Immunobiology Clinic, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Patrick Stordeur
- Immunobiology Clinic, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Denis Franchimont
- Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.,Department of Gastroenterology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
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Mulak A, Koszewicz M, Panek-Jeziorna M, Koziorowska-Gawron E, Budrewicz S. Fecal Calprotectin as a Marker of the Gut Immune System Activation Is Elevated in Parkinson's Disease. Front Neurosci 2019; 13:992. [PMID: 31611762 PMCID: PMC6776883 DOI: 10.3389/fnins.2019.00992] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Accepted: 09/03/2019] [Indexed: 12/26/2022] Open
Abstract
Introduction Alpha-synucleinopathy constituting a characteristic feature of Parkinson’s disease (PD) occurs at all levels of the brain-gut axis including the enteric nervous system (ENS). Lesions in the ENS may be connected with gut inflammation, increased intestinal permeability and dysmotility contributing to the pathogenesis of PD and its gastrointestinal manifestations. Aims To evaluate fecal calprotectin and zonulin as biomarkers of gut inflammation and intestinal barrier dysfunction in PD patients. Methods Quantitative evaluation of fecal biomarkers was performed by ELISA tests in 35 PD patients and 20 healthy controls. Additionally, patients filled out a short questionnaire concerning gastrointestinal symptoms. Results Median fecal calprotectin level (μg/g) was significantly higher in PD patients compared to the controls: 54.5 (29.0–137.9) vs. 9.7 (5.2–23.3), p < 0.0001. Applying age-related reference ranges, the increased fecal calprotectin level was found in 43% of PD patients and in none of the control subjects (p < 0.001). No correlation between fecal calprotectin level and PD duration was observed. No statistically significant difference between the groups regarding zonulin level was found. The most frequent bowel symptoms reported by PD patients included constipation (69% of subjects), feeling of incomplete evacuation (51%), bloating (51%), abdominal pain (20%), and alternating bowel movement pattern (17%). Conclusion The evaluation of fecal calprotectin level may be a useful tool to detect the signs of gut immune system activation present in a remarkable number of PD patients, also in the early stage of the disease. Calprotectin may constitute a critical link between amyloid formation and neuroinflammatory cascades serving as a prospective diagnostic and therapeutic target.
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Affiliation(s)
- Agata Mulak
- Department of Gastroenterology and Hepatology, Wrocław Medical University, Wrocław, Poland
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Cepon‐Robins TJ, Gildner TE, Schrock J, Eick G, Bedbury A, Liebert MA, Urlacher SS, Madimenos FC, Harrington CJ, Amir D, Bribiescas RG, Sugiyama LS, Snodgrass JJ. Soil‐transmitted helminth infection and intestinal inflammation among the Shuar of Amazonian Ecuador. AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 2019; 170:65-74. [DOI: 10.1002/ajpa.23897] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2018] [Revised: 06/18/2019] [Accepted: 06/19/2019] [Indexed: 12/26/2022]
Affiliation(s)
| | | | - Joshua Schrock
- Department of Anthropology University of Oregon Eugene Oregon
| | - Geeta Eick
- Department of Anthropology University of Oregon Eugene Oregon
| | - Ali Bedbury
- Department of Anthropology University of Oregon Eugene Oregon
| | - Melissa A. Liebert
- Department of Anthropology Northern Arizona University Flagstaff Arizona
| | - Samuel S. Urlacher
- Department of Evolutionary Anthropology Duke University Durham North Carolina
- Department of Anthropology Baylor University Waco Texas
| | - Felicia C. Madimenos
- Department of Anthropology Queens College ‐ City University of New York Queens New York
| | | | - Dorsa Amir
- Department of Psychology Boston College Chestnut Hill Massachusetts
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40
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Li J, Zhao X, Li X, Lu M, Zhang H. Systematic Review with Meta-Analysis: Fecal Calprotectin as a Surrogate Marker for Predicting Relapse in Adults with Ulcerative Colitis. Mediators Inflamm 2019; 2019:2136501. [PMID: 31275056 PMCID: PMC6558608 DOI: 10.1155/2019/2136501] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 05/05/2019] [Indexed: 02/07/2023] Open
Abstract
The clinical course of ulcerative colitis (UC) is featured by remission and relapse, which remains unpredictable. Recent studies revealed that fecal calprotectin (FC) could predict clinical relapse for UC patients in remission, which has not yet been well accepted. To detect the predictive value of FC for clinical relapse in adult UC patients based on updated literature, we carried out a comprehensive electronic search of PubMed, Web of Science, Embase, and the Cochrane Library to identify all eligible studies. Diagnostic accuracy including pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and pooled area under the receiver operating characteristic (AUROC) was calculated using a random effects model. Heterogeneity across studies was assessed by the I 2 metric. Sources of heterogeneity were detected using subgroup analysis. Metaregression was used to test potential factors correlated to DOR. Publication bias was assessed using Deek's funnel plots. In our study, 14 articles enrolling a total of 1110 participants were finally included, and all articles underwent a quality assessment. Pooled sensitivity, specificity, PLR, and NLR with 95% confidence intervals (CIs) were 0.75 (95% CI: 0.70-0.79), 0.77 (95% CI: 0.74-0.80), 3.45 (95% CI: 2.31-5.14), and 0.37 (95% CI: 0.28-0.49) respectively. The area under the summary receiver operating characteristic (sROC) curve was 0.82, and the diagnostic odds ratio was 10.54 (95% CI: 6.16-18.02). Our study suggested that FC is useful in predicting clinical relapse for adult UC patients in remission as a simple and noninvasive marker.
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Affiliation(s)
- Jiajia Li
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210029, China
| | - Xiaojing Zhao
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210029, China
| | - Xueting Li
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210029, China
| | - Meijiao Lu
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210029, China
| | - Hongjie Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210029, China
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Ooi CY, Syed SA, Rossi L, Garg M, Needham B, Avolio J, Young K, Surette MG, Gonska T. Impact of CFTR modulation with Ivacaftor on Gut Microbiota and Intestinal Inflammation. Sci Rep 2018; 8:17834. [PMID: 30546102 PMCID: PMC6292911 DOI: 10.1038/s41598-018-36364-6] [Citation(s) in RCA: 78] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Accepted: 11/09/2018] [Indexed: 12/16/2022] Open
Abstract
Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Next to progressive airway disease, CF is also associated with intestinal inflammation and dysbiosis. Ivacaftor, a CFTR potentiator, has improved pulmonary and nutritional status but its effects on the intestinal microbiota and inflammation are unclear. Hence, we assessed the changes on the intestinal microbial communities (16S rRNA variable 3 gene region) and inflammatory markers (calprotectin and M2-pyruvate kinase [M2-PK]) in 16 CF individuals (8 children and 8 adults) before and after (median 6.1 months) ivacaftor. Stool calprotectin significantly decreased following ivacaftor (median [IQR]: 154.4 [102.1–284.2] vs. 87.5 [19.5–190.2] mg/kg, P = 0.03). There was a significant increase in Akkermansia with ivacaftor. Increased abundance of Akkermansia was associated with normal stool M2-PK concentrations, and decreased abundances of Enterobacteriaceae correlated with decreased stool calprotectin concentrations. In summary, changes in the gut microbiome and decrease in intestinal inflammation was associated with Ivacaftor treatment among individuals with CF carrying at least one gating CFTR mutation. Thus, CFTR-modifying therapy may adequately improve the aberrant pathophysiology and milieu of the CF gut to favor a more healthy microbiota, which in turn reduces intestinal inflammation.
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Affiliation(s)
- Chee Y Ooi
- School of Women's and Children's Health, Medicine, The University of New South Wales, Sydney, NSW, Australia. .,Molecular and Integrative Cystic Fibrosis (miCF) Research Centre, Sydney Children's Hospital, Randwick, NSW, Australia. .,Department of Gastroenterology, Sydney Children's Hospital, Randwick, NSW, Australia.
| | - Saad A Syed
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada.,Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, ON, Canada.,Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Laura Rossi
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada.,Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, ON, Canada.,Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Millie Garg
- School of Women's and Children's Health, Medicine, The University of New South Wales, Sydney, NSW, Australia
| | - Bronwen Needham
- School of Women's and Children's Health, Medicine, The University of New South Wales, Sydney, NSW, Australia
| | - Julie Avolio
- Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Kelsey Young
- Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Michael G Surette
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada.,Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, ON, Canada.,Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Tanja Gonska
- Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.,Translational Medicine, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
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The Therapeutic Effect of a Multistrain Probiotic on Diarrhea-Predominant Irritable Bowel Syndrome: A Pilot Study. Gastroenterol Res Pract 2018; 2018:8791916. [PMID: 30622561 PMCID: PMC6304810 DOI: 10.1155/2018/8791916] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 10/15/2018] [Indexed: 12/20/2022] Open
Abstract
Backgrounds Recent studies suggest that diarrhea-predominant irritable bowel syndrome (IBS) is associated with intestinal bacterial microflora, colonic inflammation, and small intestinal bacterial overgrowth (SIBO). The purpose of this study was to evaluate the effect of a multistrain probiotic intake on these associated factors in patients with diarrhea-predominant IBS. Methods The recruited volunteers were adults who were diagnosed with diarrhea-predominant IBS according to the Rome III criteria. After 8 weeks of probiotic ingestion, changes in gastrointestinal symptoms, fecal microbiome, SIBO, and fecal calprotectin were determined. Results There was an increase in beneficial bacteria (41.2 ± 16.8% vs. 53.7 ± 15.3%, P = 0.018) and a decrease in harmful bacteria (13.0 ± 13.9% vs. 4.7 ± 4.0%, P = 0.010) in the microbial stool analysis. The SIBO prevalence also decreased at the end of treatment. However, the average levels of fecal calprotectin showed a decreasing tendency, without reaching statistical significance (364.4 ± 729.1 mg/kg vs. 200.9 ± 347.6 mg/kg, P = 0.375). Conclusion Treatment with a multistrain probiotic for 8 weeks led to significant increases in beneficial bacteria in the gut as well as the improvement of gastrointestinal symptoms. This study is registered at the Clinical Research Information Service (KCT0002906).
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Padoan A, D’Incà R, Scapellato ML, De Bastiani R, Caccaro R, Mescoli C, Moz S, Bozzato D, Zambon CF, Lorenzon G, Rugge M, Plebani M, Basso D. Improving IBD diagnosis and monitoring by understanding preanalytical, analytical and biological fecal calprotectin variability. ACTA ACUST UNITED AC 2018; 56:1926-1935. [DOI: 10.1515/cclm-2018-0134] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Accepted: 04/03/2018] [Indexed: 12/12/2022]
Abstract
Abstract
Background:
The appropriate clinical use of fecal calprotectin (fCal) might be compromised by incomplete harmonization between assays and within- and between-subjects variability. Our aim was to investigate the analytical and biological variability of fCal in order to provide tools for interpreting fCal in the clinical setting.
Methods:
Experiments were conducted to investigate the effects of temperature and storage time on fCal. Thirty-nine controls were enrolled to verify biological variability, and a case-control study was conducted on 134 controls and 110 IBD patients to compare the clinical effectiveness of three different fCal assays: ELISA, CLIA and turbidimetry.
Results:
A 12% decline in fCal levels was observed within 24 h following stool collection irrespective of storage temperature. Samples were unstable following a longer storage time interval at room temperature. Within- and between-subjects fCal biological variability, at 31% and 72% respectively, resulted in a reference change value (RCV) in the region of 100%. fCal sensitivity in distinguishing between controls and IBD patients is satisfactory (68%), and the specificity high (93%) among young (<65 years), but not among older (≥65 years) subjects (ROC area: 0.584; 95% CI: 0.399–0.769). Among the young, assays have different optimal thresholds (120 μg/g for ELISA, 50 μg/g for CLIA and 100 μg/g for turbidimetry).
Conclusions:
We recommend a standardized preanalytical protocol for fCal, avoiding storage at room temperature for more than 24 h. Different cutoffs are recommended for different fCal assays. In monitoring, the difference between two consecutive measurements appears clinically significant when higher than 100%, the fCal biological variability-derived RCV.
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Affiliation(s)
- Andrea Padoan
- Department of Medicine – DIMED , University of Padova , Padova , Italy
| | - Renata D’Incà
- Division of Gastroenterology , University Hospital , Padova , Italy
| | - Maria Luisa Scapellato
- Department of Cardiologic, Thoracic and Vascular Sciences , Preventive Medicine and Risk Assessment Unit , University Hospital of Padova , Padova , Italy
| | - Rudi De Bastiani
- Italian Association for Gastroenterology in Primary Care (GICA-CP) , Feltre , Italy
| | - Roberta Caccaro
- Division of Gastroenterology , University Hospital , Padova , Italy
| | - Claudia Mescoli
- Department of Medicine – DIMED , University of Padova , Padova , Italy
| | - Stefania Moz
- Department of Medicine – DIMED , University of Padova , Padova , Italy
| | - Dania Bozzato
- Department of Medicine – DIMED , University of Padova , Padova , Italy
| | | | - Greta Lorenzon
- Division of Gastroenterology , University Hospital , Padova , Italy
| | - Massimo Rugge
- Department of Medicine – DIMED , University of Padova , Padova , Italy
| | - Mario Plebani
- Department of Medicine – DIMED , University of Padova , Padova , Italy
| | - Daniela Basso
- Department of Medicine – DIMED , University of Padova , Padova , Italy
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D'Angelo F, Felley C, Frossard JL. Calprotectin in Daily Practice: Where Do We Stand in 2017? Digestion 2018; 95:293-301. [PMID: 28511188 DOI: 10.1159/000476062] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Accepted: 04/23/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND To make a distinction between organic and functional disease is essential for gastroenterologists in their daily practice, but it may be challenging, given the variety and aspecificity of gastrointestinal symptoms among the general population. The clinician aim is to avoid diagnostic delay and to restrict unnecessary invasive and expensive exams. SUMMARY Faecal markers, in particular faecal calprotectin (FC), have given proof of being reliable markers of intestinal inflammation with good clinical sensitivity. Calprotectin is useful in the differential diagnosis between inflammatory bowel disease and irritable bowel syndrome, as well as in the follow-up of inflammatory bowel disease patients and in predicting treatment response, with an excellent correlation with endoscopic activity. Its role in collagenous colitis and infectious colitis is less clear and still under investigation. Key Message: Despite the growing evidence supporting its use, many clinicians are uncomfortable in dosing FC, due to its low specificity and the variability of cut-off values. Indeed there are no clear guidelines about how to manage patients with intermediate levels of FC. The aim of this article is to review recent literature on calprotectin and its use. The strong points and the limits of FC measurement will be analysed, and a practical approach in the daily clinical routine will be proposed.
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Affiliation(s)
- Fabrizia D'Angelo
- Service of Gastroenterology and Hepatology, Geneva University Hospital, Geneva, Switzerland
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45
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Shores DR, Everett AD. Children as Biomarker Orphans: Progress in the Field of Pediatric Biomarkers. J Pediatr 2018; 193:14-20.e31. [PMID: 29031860 PMCID: PMC5794519 DOI: 10.1016/j.jpeds.2017.08.077] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 08/04/2017] [Accepted: 08/30/2017] [Indexed: 12/20/2022]
Affiliation(s)
- Darla R Shores
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD.
| | - Allen D Everett
- Division of Cardiology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD
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46
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Unsuspected Small-Bowel Crohn's Disease in Elderly Patients Diagnosed by Video Capsule Endoscopy. DIAGNOSTIC AND THERAPEUTIC ENDOSCOPY 2018; 2018:9416483. [PMID: 29622900 PMCID: PMC5830029 DOI: 10.1155/2018/9416483] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Revised: 11/27/2017] [Accepted: 12/12/2017] [Indexed: 12/13/2022]
Abstract
Background Video capsule endoscopy (VCE) is increasingly performed among the elderly for obscure bleeding. Our aim was to report on the utility of VCE to uncover unsuspected Crohn's disease (CD) in elderly patients. Methods Retrospective review of VCE performed in elderly patients (≥70 y) at a tertiary hospital (2010-2015). All underwent prior negative bidirectional endoscopies. CD diagnosis was based on consistent endoscopic findings, exclusion of other causes, and a Lewis endoscopic score (LS) > 790 (moderate-to-severe inflammation). Those with lower LS (350-790) required histological confirmation. Known IBD cases were excluded. Results 197 VCE were performed (mean age 78; range 70-93). Main indications were iron deficiency anemia (IDA), occult GI bleeding (OGIB), chronic abdominal pain, or diarrhea. Eight (4.1%) were diagnosed as CD based on the aforementioned criteria. Fecal calprotectin (FCP) was elevated in 7/8 (mean 580 μg/g). Mean LS was 1824. Small-bowel CD detected by VCE led to a change in management in 4/8. One patient had capsule retention secondary to NSAID induced stricture, requiring surgical retrieval. Conclusions VCE can be safely performed in the elderly. A proportion of cases may have unsuspected small-bowel CD despite negative endoscopies. FCP was the best screening test. Diagnosis frequently changed management.
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Abstract
Calprotectin is a 36kDa member of the S100 family of proteins. It is derived predominantly from neutrophils and has direct antimicrobial effects and a role within the innate immune response. Calprotectin is found in various body fluids in proportion to the degree of any existing inflammation and its concentration in feces is about six times that of plasma. Measurement of fecal calprotectin is a useful surrogate marker of gastrointestinal inflammation. It has a high negative predictive value in ruling out inflammatory bowel disease (IBD) in undiagnosed, symptomatic patients and a high sensitivity for diagnosing the disease making it useful as a tool for prioritising endoscopy. In patients with known IBD, fecal calprotectin can be a useful tool to assist management, providing evidence of relapse or mucosal healing to enable therapy to be intensified or reduced. There are a number of commercial calprotectin assays with marked difference in performance as judged by external quality assessment and at present no standardised reference material exists. Various factors may affect results including age, medication and day to day variation. Laboratories should therefore be mindful of the characteristics of their own assay and factors that may affect results.
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Affiliation(s)
- Ruth M Ayling
- FRCPath Consultant Chemical Pathologist, Clinical Biochemistry, Pathology and Pharmacy Building, Royal London Hospital, London, United Kingdom
| | - Klaartje Kok
- MRCP Consultant Gastroenterologist, Barts Health NHS Trust, London, United Kingdom
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48
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Almousa AA, Morris M, Fowler S, Jones J, Alcorn J. Elevation of serum pyruvate kinase M2 (PKM2) in IBD and its relationship to IBD indices. Clin Biochem 2017; 53:19-24. [PMID: 29273328 DOI: 10.1016/j.clinbiochem.2017.12.007] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Revised: 12/04/2017] [Accepted: 12/17/2017] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Endoscopy remains the gold standard to diagnose and evaluate inflammatory bowel disease (IBD) activity. Current biomarkers or their combinations cannot adequately predict IBD risk, diagnosis, progression or relapse, and response to therapy. Pyruvate kinase M2 (PKM2) is emerging as a significant mediator of the inflammatory process. We aimed to assess levels of serum PKM2 in healthy and newly diagnosed IBD patients and its relationship with IBD indices and microbiota changes. DESIGN AND METHODS IBD serum samples from newly diagnosed patients were collected and analyzed using a PKM2-ELISA and correlated with disease activity scores, IBD disease type, and intestinal microbiota. Furthermore, we tested the genetic and protein expression of PKM2 in an in vitro intestinal cell model of inflammation. RESULTS Serum PKM2 levels were 6-fold higher in IBD patients compared to healthy controls, with no sensitivity to disease phenotype (Crohn's Disease or Ulcerative Colitis) or localization of inflammation. Serum PKM2 had considerably less interindividual variability than established IBD fecal biomarkers. A positive Pearson correlation (r=0.6121) existed between serum PKM2 and Bacteroidetes fecal levels in Crohn's disease (CD), while a negative (r=-0.6128) correlation was observed with Actinobacteria fecal levels. Furthermore, LPS (500ng/mL) significantly increased PKM2 expression in vitro, which was significantly suppressed by an anti-inflammatory flaxseed bioactive agent. CONCLUSION Our data suggests PKM2 as a putative biomarker for IBD and the dysbiosis of microflora in CD. Investigations involving larger number of clinical patients are necessary to validate its use as a serum biomarker of IBD.
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Affiliation(s)
- Ahmed A Almousa
- Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan, Canada
| | - Marc Morris
- Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan, Canada
| | - Sharyle Fowler
- Department of Gastroenterology, College of Medicine, University of Saskatchewan, Saskatoon, Canada
| | - Jennifer Jones
- Division of Digestive Care & Endoscopy, Department of Community Health and Epidemiology, Dalhousie University, Halifax, Canada
| | - Jane Alcorn
- Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan, Canada.
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49
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Fecal Calprotectin, Elastase, and Alpha-1-Antitrypsin Levels After Roux-en-Y Gastric Bypass; Calprotectin Is Significantly Elevated in the Majority of Patients. Obes Surg 2017; 26:2974-2980. [PMID: 27216731 PMCID: PMC5118387 DOI: 10.1007/s11695-016-2222-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
BACKGROUND Roux-en-Y gastric bypass (RYGB) causes several alterations in gastrointestinal function. We hypothesized that levels of three commonly used fecal tests change after RYGB. METHODS Fecal levels of calprotectin, elastase, and alpha-1-antitrypsin were determined in 122 patients without signs of gastrointestinal disease 1 to 2 years after RYGB. Medians, distribution of values, and the percentage of patients with levels above or below reference values were determined. RESULTS Median fecal calprotectin level was 163.5 (<30-1587) μg/g; in 87 % of patients, it was above the reference value (<50 μg/g). Median fecal elastase level was 444 (<15-647) μg/g; 13 % was below the reference value (>200 μg/g). Median fecal alpha-1-antitrypsin level was 0.51 (<0.20-2.20) mg/g, comparable to the reference values. CONCLUSIONS Fecal calprotectin levels are significantly higher than the reference value in most patients after RYGB. Fecal elastase is significantly lower. This might indicate that the validity of fecal calprotectin testing is impaired after RYGB and the specificity for fecal elastase is decreased. Clinical awareness of altered fecal markers after RYGB is essential to prevent unnecessary diagnostic tests, such as colonoscopy. Fecal alpha-1-antitrypsin is not influenced by RYGB.
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50
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Garg M, Leach ST, Pang T, Needham B, Coffey MJ, Katz T, Strachan R, Widger J, Field P, Belessis Y, Chuang S, Day AS, Jaffe A, Ooi CY. Age-related levels of fecal M2-pyruvate kinase in children with cystic fibrosis and healthy children 0 to 10years old. J Cyst Fibros 2017; 17:109-113. [PMID: 28754328 DOI: 10.1016/j.jcf.2017.07.011] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Revised: 07/11/2017] [Accepted: 07/11/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND The pathogenesis of gut inflammation, bacterial dysbiosis and increased rates of malignancy in CF is unclear. Fecal M2-pyruvate kinase (M2-PK) is a biomarker indicative of cellular proliferation that may be raised in intestinal malignancy and inflammation. Biomarkers, including M2-PK, may be useful in assessing effects of novel therapies on the gastrointestinal tract. METHODS M2-PK was measured in stools collected from patients with CF and HC (0-10years). Linear mixed model analysis was used. RESULTS M2-PK levels did not significantly change in children with CF (36 patients, 77 samples) (P=0.998) or HC (45 patients, 45 samples) (P=0.21), over the age range 0-10years. Patients with CF had elevated M2-PK compared to HC (median [IQR; range]: 10.7 [5.7-28.6; 1.0-239.1] (n=77) vs. 1.0 [1.0-1.0; 1.0-50.0] (n=45) U/mL, respectively; P=0.001). CONCLUSIONS Fecal M2-PK was elevated in children with CF compared with HC during infancy and throughout childhood suggesting abnormalities in the CF gut exist in early life.
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Affiliation(s)
- Millie Garg
- School of Women and Children's Health, Medicine, The University of New South Wales, High Street, Sydney Children's Hospital, Randwick 2031, New South Wales, Australia
| | - Steven T Leach
- School of Women and Children's Health, Medicine, The University of New South Wales, High Street, Sydney Children's Hospital, Randwick 2031, New South Wales, Australia
| | - Tamara Pang
- School of Women and Children's Health, Medicine, The University of New South Wales, High Street, Sydney Children's Hospital, Randwick 2031, New South Wales, Australia
| | - Bronwen Needham
- Sydney Medical Program, The University of Sydney, Camperdown 2050, New South Wales, Australia
| | - Michael J Coffey
- School of Women and Children's Health, Medicine, The University of New South Wales, High Street, Sydney Children's Hospital, Randwick 2031, New South Wales, Australia
| | - Tamarah Katz
- Department of Nutrition and Dietetics, Sydney Children's Hospital, High Street, Randwick 2031, New South Wales, Australia
| | - Roxanne Strachan
- Department of Respiratory Medicine, Sydney Children's Hospital, High Street, Randwick 2031, New South Wales, Australia
| | - John Widger
- School of Women and Children's Health, Medicine, The University of New South Wales, High Street, Sydney Children's Hospital, Randwick 2031, New South Wales, Australia; Department of Respiratory Medicine, Sydney Children's Hospital, High Street, Randwick 2031, New South Wales, Australia
| | - Penelope Field
- School of Women and Children's Health, Medicine, The University of New South Wales, High Street, Sydney Children's Hospital, Randwick 2031, New South Wales, Australia; Department of Respiratory Medicine, Sydney Children's Hospital, High Street, Randwick 2031, New South Wales, Australia
| | - Yvonne Belessis
- School of Women and Children's Health, Medicine, The University of New South Wales, High Street, Sydney Children's Hospital, Randwick 2031, New South Wales, Australia; Department of Respiratory Medicine, Sydney Children's Hospital, High Street, Randwick 2031, New South Wales, Australia
| | - Sandra Chuang
- School of Women and Children's Health, Medicine, The University of New South Wales, High Street, Sydney Children's Hospital, Randwick 2031, New South Wales, Australia; Department of Respiratory Medicine, Sydney Children's Hospital, High Street, Randwick 2031, New South Wales, Australia
| | - Andrew S Day
- Department of Paediatrics, University of Otago, Riccarton Ave, Christchurch 8011, Canterbury, New Zealand
| | - Adam Jaffe
- School of Women and Children's Health, Medicine, The University of New South Wales, High Street, Sydney Children's Hospital, Randwick 2031, New South Wales, Australia; Department of Respiratory Medicine, Sydney Children's Hospital, High Street, Randwick 2031, New South Wales, Australia
| | - Chee Y Ooi
- School of Women and Children's Health, Medicine, The University of New South Wales, High Street, Sydney Children's Hospital, Randwick 2031, New South Wales, Australia; Department of Gastroenterology, Sydney Children's Hospital, High Street, Randwick 2031, New South Wales, Australia.
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