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Haider MB, Al Sbihi A, Reddy SN, Green P. Prevalence of malignant neoplasms in celiac disease patients - a nationwide United States population-based study. World J Clin Oncol 2024; 15:1048-1060. [PMID: 39193153 PMCID: PMC11346075 DOI: 10.5306/wjco.v15.i8.1048] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 06/10/2024] [Accepted: 06/27/2024] [Indexed: 08/16/2024] Open
Abstract
BACKGROUND Celiac disease (CeD) is an autoimmune disorder triggered by the immune response to gluten in genetically predisposed individuals. Recent research has unveiled a heightened risk of developing specific malignant neoplasms (MN) and various malignancies, including gastrointestinal, lymphomas, skin, and others, in individuals with CeD. AIM To investigate the prevalence of MN in hospitalized CeD patients in the United States. METHODS Using data from the National Inpatient Sample spanning two decades, from January 2000 to December 2019, we identified 529842 CeD patients, of which 78128 (14.75%) had MN. Propensity score matching, based on age, sex, race, and calendar year, was employed to compare CeD patients with the general non-CeD population at a 1:1 ratio. RESULTS Positive associations were observed for several malignancies, including small intestine, lymphoma, nonmelanoma skin, liver, melanoma skin, pancreas myelodysplastic syndrome, biliary, stomach, and other neuroendocrine tumors (excluding small and large intestine malignant carcinoid), leukemia, uterus, and testis. Conversely, CeD patients exhibited a reduced risk of respiratory and secondary malignancies. Moreover, certain malignancies showed null associations with CeD, including head and neck, nervous system, esophagus, colorectal, anus, breast, malignant carcinoids, bone and connective tissues, myeloma, cervix, and ovary cancers. CONCLUSION Our study is unique in highlighting the detailed results of positive, negative, or null associations between different hematologic and solid malignancies and CeD. Furthermore, it offers insights into evolving trends in CeD hospital outcomes, shedding light on advancements in its management over the past two decades. These findings contribute valuable information to the understanding of CeD's impact on health and healthcare utilization.
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Affiliation(s)
- Maryam Bilal Haider
- Department of Gastroenterology, Northshore University Health System, Evanston, IL 60201, United States
| | - Ali Al Sbihi
- Department of Hematology/Oncology, University of Miami Miller School of Medicine, Miami, FL 33101, United States
| | - Sushmitha Nanja Reddy
- Department of Hematology/Oncology, Karmanos Cancer Institute/Wayne State University, Detroit, MI 48235, United States
| | - Peter Green
- Celiac Disease Center, Columbia University, New York, NY 10032, United States
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Gordon ER, Adeuyan O, Kwinta BD, Schreidah CM, Fahmy LM, Queen D, Trager MH, Magro CM, Geskin LJ. Exploring cutaneous lymphoproliferative disorders in the wake of COVID-19 vaccination. SKIN HEALTH AND DISEASE 2024; 4:e367. [PMID: 38846690 PMCID: PMC11150739 DOI: 10.1002/ski2.367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 02/08/2024] [Accepted: 03/01/2024] [Indexed: 06/09/2024]
Abstract
Background Individual reports have described lymphoproliferative disorders (LPDs) and cutaneous lymphomas emerging after administration of the COVID-19 vaccine; however, the relationship between reactions and vaccine types has not yet been examined. Objective Determine if there are cases of cutaneous LPDs associated with certain COVID-19 vaccines and their outcomes. Methods We analysed PubMed, the Vaccine Adverse Events Reporting System (VAERS), and our database for instances of biopsy-proven LPDs following COVID-19 vaccines. Results Fifty cases of biopsy-proven LPDs arising after COVID-19 vaccination were found: 37 from medical literature, 11 from VAERS and two from our institution. Geographical distribution revealed the most cases in the United States, Italy, and Greece, with single cases in Spain, Colombia, Canada, Japan, and Romania. The average age of patients was 53; with a slight male predominance (male-to-female ratio of 1.5:1). The Pfizer-BioNTech vaccine was associated with LPDs in 36/50 (72%) cases, aligning with its 70% share of the global vaccine market. Histopathology revealed CD30+ in 80% of cases. The most prevalent form of LPD was lymphomatoid papulosis (LyP, 30%). All reported cases produced favourable outcomes (either complete or near-complete remission). Therapeutic approaches ranged from observation to treatment with steroids, methotrexate, or excision. Conclusion LPDs after COVID-19 vaccination appear in the context of the same vaccines (proportionally to their global market shares), share clinical and pathological findings, and have indolent, self-limited character.
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Affiliation(s)
- Emily R. Gordon
- Vagelos College of Physicians & SurgeonsColumbia UniversityNew YorkNYUSA
| | - Oluwaseyi Adeuyan
- Vagelos College of Physicians & SurgeonsColumbia UniversityNew YorkNYUSA
| | - Bradley D. Kwinta
- Department of DermatologyColumbia University Irving Medical CenterNew YorkNYUSA
| | | | - Lauren M. Fahmy
- Vagelos College of Physicians & SurgeonsColumbia UniversityNew YorkNYUSA
| | - Dawn Queen
- Department of DermatologyColumbia University Irving Medical CenterNew YorkNYUSA
| | - Megan H. Trager
- Department of DermatologyColumbia University Irving Medical CenterNew YorkNYUSA
| | - Cynthia M. Magro
- Department of Pathology and Laboratory MedicineWeill Cornell MedicineNew YorkNYUSA
| | - Larisa J. Geskin
- Department of DermatologyColumbia University Irving Medical CenterNew YorkNYUSA
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Gordon ER, Kwinta BD, Schreidah CM, Fahmy LM, Adeuyan O, Queen D, Trager MH, Magro CM, Geskin LJ. Cutaneous lymphoproliferative disorders after COVID-19 vaccination: clinical presentation, histopathology, and outcomes. Leuk Lymphoma 2024; 65:48-54. [PMID: 37861685 DOI: 10.1080/10428194.2023.2270766] [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: 07/27/2023] [Accepted: 10/08/2023] [Indexed: 10/21/2023]
Abstract
Individual reports described lymphoproliferative disorders (LPDs) after COVID-19 vaccination; however, the relationship between cases is unexamined. We aim to determine if there are cases of cutaneous LPDs associated with COVID-19 vaccination and their outcomes. We present a review of world literature, vaccine registries, and two unreported cases of LPDs after COVID-19 vaccination. Review of the medical literature, VAERS, and our two cases reveal predominance of Pfizer-BioNTech vaccine, younger patients, and males. All cases resulted in favorable outcomes. Approximately 84% of cases demonstrated CD30+ positivity in their skin biopsies, suggesting that an antigenic trigger may lead to a type IV adaptive immune response, with clonal expansion of CD30+ T-cells and subsequent oncogenic mutational hits eventuating in transient LPDs. LPDs after COVID-19 vaccination appear in the context of the same vaccines (proportionally to their global market shares), share clinical and pathological findings, and have indolent, self-limited character.
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Affiliation(s)
- Emily R Gordon
- Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA
| | - Bradley D Kwinta
- Department of Dermatology, Columbia University Irving Medical Center, New York, NY, USA
| | - Celine M Schreidah
- Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA
| | - Lauren M Fahmy
- Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA
| | - Oluwaseyi Adeuyan
- Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA
| | - Dawn Queen
- Department of Dermatology, Columbia University Irving Medical Center, New York, NY, USA
| | - Megan H Trager
- Department of Dermatology, Columbia University Irving Medical Center, New York, NY, USA
| | - Cynthia M Magro
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Larisa J Geskin
- Department of Dermatology, Columbia University Irving Medical Center, New York, NY, USA
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Alhamadh MS, Alhowaish TS, Mathkour A, Altamimi B, Alheijani S, Alrashid A. Infection Risk, Mortality, and Hypogammaglobulinemia Prevalence and Associated Factors in Adults Treated with Rituximab: A Tertiary Care Center Experience. Clin Pract 2023; 13:1286-1302. [PMID: 37987416 PMCID: PMC10660466 DOI: 10.3390/clinpract13060115] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 10/09/2023] [Accepted: 10/18/2023] [Indexed: 11/22/2023] Open
Abstract
BACKGROUND Rituximab is a human monoclonal antibody directed against the B-cell transmembrane protein CD20. Although well-tolerated, given its mechanism of action, rituximab can induce a state of severe immunosuppression, increasing the risk of opportunistic and fulminant infection and mortality. AIM To evaluate the risk of infection, mortality, and hypogammaglobulinemia and their associated factors among rituximab receivers. METHOD This was a single-center retrospective cohort study of adults treated with rituximab for various indications. Hypogammaglobulinemia was defined by a cut-off value below the normal limit (an IgG level of <7.51 g/L, an IgM level of <0.46 g/L, and/or an IgA level of <0.82 g/L). Patients who met the definition of hypogammaglobinemia solely based on IgA were excluded. Severe infection was defined as any infection that required intensive care unit admission. RESULTS A total of 137 adults with a mean age of 47.69 ± 18.86 years and an average BMI of 28.57 ± 6.55 kg/m2 were included. Hematological malignancies and connective tissue diseases were the most common primary diagnoses for which rituximab was used. More than half of the patients received the 375 mg/m2 dose. Rituximab's mean cumulative dose was 3216 ± 2282 mg, and the overall mortality rate was 22.6%. Hypogammaglobulinemia was diagnosed in 43.8% of the patients, and it was significantly more prevalent among males and the 375 mg/m2 and 500 mg doses. Hematological malignancy was the only predictor for infection. Patients with blood type AB or B, hematological malignancies, and corticosteroids had a significantly higher mortality rate. Receiving the 1000 mg dose and having a low CD19 were associated with a significantly lower risk of infection and mortality, respectively. CONCLUSIONS Hypogammaglobulinemia was diagnosed in 43.8% of the patients, and it was significantly more common among males and the 375 mg/m2 and 500 mg doses. Hematological malignancies were significantly associated with higher infection and mortality rates, while corticosteroids were significantly associated with a higher mortality. Since the culprit of mortality was infection, these findings highlight the critical need for more frequent immunological monitoring during rituximab treatment period to mitigate the burden of infection and identify candidates for immunoglobulin replacement.
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Affiliation(s)
- Moustafa S. Alhamadh
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Ministry of the National Guard-Health Affairs, Riyadh 14611, Saudi Arabia
- King Abdullah International Medical Research Center, Ministry of the National Guard-Health Affairs, Riyadh 11481, Saudi Arabia; (T.S.A.)
| | - Thamer S. Alhowaish
- King Abdullah International Medical Research Center, Ministry of the National Guard-Health Affairs, Riyadh 11481, Saudi Arabia; (T.S.A.)
- Department of Neurology, King Abdulaziz Medical City, Ministry of the National Guard-Health Affairs, Riyadh 11426, Saudi Arabia
| | | | - Bayan Altamimi
- King Abdullah International Medical Research Center, Ministry of the National Guard-Health Affairs, Riyadh 11481, Saudi Arabia; (T.S.A.)
- Department of Medicine, Division of Rheumatology, King Abdulaziz Medical City, Ministry of the National Guard-Health Affairs, Riyadh 11426, Saudi Arabia
| | - Shahd Alheijani
- College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
| | - Abdulrahman Alrashid
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Ministry of the National Guard-Health Affairs, Riyadh 14611, Saudi Arabia
- King Abdullah International Medical Research Center, Ministry of the National Guard-Health Affairs, Riyadh 11481, Saudi Arabia; (T.S.A.)
- Department of Medicine, Division of Rheumatology, King Abdulaziz Medical City, Ministry of the National Guard-Health Affairs, Riyadh 11426, Saudi Arabia
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Treppo E, Toffolutti F, Manfrè V, Taborelli M, De Marchi G, De Vita S, Serraino D, Quartuccio L. Risk of Cancer in Connective Tissue Diseases in Northeastern Italy over 15 Years. J Clin Med 2022; 11:jcm11154272. [PMID: 35893361 PMCID: PMC9332163 DOI: 10.3390/jcm11154272] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 07/08/2022] [Accepted: 07/20/2022] [Indexed: 11/30/2022] Open
Abstract
Objective: To evaluate cancer risk among individuals with connective tissue disease (CTD) in Friuli Venezia Giulia, northern Italy. Methods: A population-based cohort study was conducted based on data from health records available in the regional healthcare database. Demographic characteristics, hospital discharges, exemption from medical charges, drug prescriptions, were individually matched with data from the population-based cancer registry. Cancer risk was assessed in people diagnosed with the following diseases: systemic lupus erythematosus (SLE), Sjögren’s syndrome (SS), systemic sclerosis (SSc), polymyositis (PM), and dermatomyositis (DM). Results: In all, 2504 patients were followed for a total of 18,006 person-years (median follow-up: 6.8 years). After 5 and 10 years of follow-up, the cumulative cancer incidence was 2.6% and 8.5%, respectively. The most common cancers were breast (n = 34), lung (n = 24), colon–rectum–anus (n = 20), and non-Hodgkin lymphomas (NHL) (n = 20). Overall, no excess cancer risk was noted (SIR = 0.87), whereas the number of observed NHL cases was more than two-fold significantly higher than expected (SIR = 2.52). The subgroup analysis showed a higher risk of NHL among SS patients (SIR = 3.84) and SLE patients (SIR = 2.69). Conversely, the study population showed a decreased risk for breast cancers (SIR = 0.61) and corpus uteri (SIR = 0.21). Conclusions: The incidence of NHL was higher among patients with SS and SLE. Careful surveillance for hematological malignancies in these patients is recommended.
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Affiliation(s)
- Elena Treppo
- Division of Rheumatology, Academic Hospital “Santa Maria della Misericordia”, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy; (E.T.); (V.M.); (G.D.M.); (S.D.V.)
- Department of Medicine (DAME), University of Udine, Via Colugna 50, 33100 Udine, Italy
| | - Federica Toffolutti
- Unit of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Via F. Gallini 2, 33081 Aviano, Italy; (F.T.); (M.T.); (D.S.)
| | - Valeria Manfrè
- Division of Rheumatology, Academic Hospital “Santa Maria della Misericordia”, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy; (E.T.); (V.M.); (G.D.M.); (S.D.V.)
- Department of Medicine (DAME), University of Udine, Via Colugna 50, 33100 Udine, Italy
| | - Martina Taborelli
- Unit of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Via F. Gallini 2, 33081 Aviano, Italy; (F.T.); (M.T.); (D.S.)
| | - Ginevra De Marchi
- Division of Rheumatology, Academic Hospital “Santa Maria della Misericordia”, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy; (E.T.); (V.M.); (G.D.M.); (S.D.V.)
| | - Salvatore De Vita
- Division of Rheumatology, Academic Hospital “Santa Maria della Misericordia”, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy; (E.T.); (V.M.); (G.D.M.); (S.D.V.)
- Department of Medicine (DAME), University of Udine, Via Colugna 50, 33100 Udine, Italy
| | - Diego Serraino
- Unit of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Via F. Gallini 2, 33081 Aviano, Italy; (F.T.); (M.T.); (D.S.)
- Friuli Venezia Giulia Cancer Registry, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Via F. Gallini 2, 33081 Aviano, Italy
| | - Luca Quartuccio
- Division of Rheumatology, Academic Hospital “Santa Maria della Misericordia”, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy; (E.T.); (V.M.); (G.D.M.); (S.D.V.)
- Department of Medicine (DAME), University of Udine, Via Colugna 50, 33100 Udine, Italy
- Correspondence: ; Tel.: +39-043-255-9808; Fax: +39-043-255-9472
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Pelizzaro F, Marsilio I, Fassan M, Piazza F, Barberio B, D’Odorico A, Savarino EV, Farinati F, Zingone F. The Risk of Malignancies in Celiac Disease-A Literature Review. Cancers (Basel) 2021; 13:cancers13215288. [PMID: 34771450 PMCID: PMC8582432 DOI: 10.3390/cancers13215288] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 10/15/2021] [Accepted: 10/19/2021] [Indexed: 12/14/2022] Open
Abstract
Celiac disease (CeD) is an immune-mediated enteropathy precipitated by ingestion of gluten in genetically predisposed individuals. Considering that CeD affects approximately 1% of the Western population, it may be considered a global health problem. In the large majority of cases, CeD has a benign course, characterized by the complete resolution of symptoms and a normal life expectancy after the beginning of a gluten-free-diet (GFD); however, an increased risk of developing malignancies, such as lymphomas and small bowel carcinoma (SBC), has been reported. In particular, enteropathy-associated T-cell lymphoma (EATL), a peculiar type of T-cell lymphoma, is characteristically associated with CeD. Moreover, the possible association between CeD and several other malignancies has been also investigated in a considerable number of studies. In this paper, we aim to provide a comprehensive review of the current knowledge about the associations between CeD and cancer, focusing in particular on EATL and SBC, two rare but aggressive malignancies.
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Affiliation(s)
- Filippo Pelizzaro
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Ilaria Marsilio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Matteo Fassan
- Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University Hospital of Padova, 35128 Padova, Italy;
- Veneto Oncology Institute, IOV-IRCCS, 35128 Padova, Italy
| | - Francesco Piazza
- Department of Medicine, Hematology, University Hospital of Padova, 35128 Padova, Italy;
| | - Brigida Barberio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Anna D’Odorico
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Edoardo V. Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Fabiana Zingone
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
- Correspondence:
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Huang HS, Chu SC, Chen PC, Lee MH, Huang CY, Chou HM, Chu TY. Insuline-Like Growth Factor-2 (IGF2) and Hepatocyte Growth Factor (HGF) Promote Lymphomagenesis in p53-null Mice in Tissue-specific and Estrogen-signaling Dependent Manners. J Cancer 2021; 12:6021-6030. [PMID: 34539876 PMCID: PMC8425200 DOI: 10.7150/jca.60120] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 07/31/2021] [Indexed: 01/04/2023] Open
Abstract
Background: Trp53-/- mice are prone to develop lymphomas at old ages. Factors promoting this tumorigenesis are unknown. Here, we showed human ovulatory follicular fluid (FF) largely promotes lymphomagenesis in Trp53-/- mice at earlier ages. Meanwhile, we clarified that IGF2 and HGF are important cell transforming factors within FF. Methods: To induce tumor formation, 5% FFs, 100 ng/ml IGF2, 20 ng/ml HGF, or both IGF2 and HGF in a volume of 200 µl PBS, was injected into 8-wk-old female Trp53 -/- mice at the mammary fat pad. The injection was repeated weekly for up to 7 weeks or extending to 13 weeks to observe the accumulative incidence of lymphomagenesis. Immunohistochemistry staining and gene rearrangement analysis were used to identify the tumor type. Results: By injecting FF into the mammary fat pad weekly, lymphomas developed in 8/16 (50%) of mice by seven weeks. We identified IGF2 and HGF in FF is largely responsible for this activity. The same weekly injection of IGF2, HGF, and their combination induced lymphomas in 4/11 (36%), 3/8 (38%), and 6/9 (67%) mice, respectively. Interestingly, tumorigenesis was induced only when those were injected into the adipose tissues in the mammary gland, but not when injected into non-adipose sites. We also found this tumor-promoting activity is estradiol (E2)-dependent and relies on estrogen receptor (ER) α expression in the adipose stroma. No tumor or only tiny tumor was yielded when the ovaries were resected or when ER is antagonized. Finally, an extension of the weekly FF-injection to 13 weeks did not further increase the lymphomagenesis rate, suggesting an effect on pre-initiated cancer cells. Conclusions: Taken together, the study disclosed a robust tumor-promoting effect of IGF2 and HGF in the p53 loss-initiated lymphomagenesis depending on an adipose microenvironment in the presence of E2. In light of the clarity of this spontaneous tumor promotion model, we provide a new tool for studying p53-mediated lymphomagenesis and suggest that, as a chemoprevention test, this is a practical model to perform.
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Affiliation(s)
- Hsuan-Shun Huang
- Center for Prevention and Therapy of Gynecological Cancers, Department of Research, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan, ROC
| | - Sung-Chao Chu
- Department of Hematology and Oncology, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan, ROC.,School of Medicine, College of Medicine, Tzu Chi University, Hualien 970, Taiwan, ROC
| | - Pao-Chu Chen
- Department of Obstetrics & Gynecology, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan, ROC
| | - Ming-Hsun Lee
- Department of Pathology, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan, ROC
| | - Chi-Ya Huang
- Center for Prevention and Therapy of Gynecological Cancers, Department of Research, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan, ROC
| | - Hsien-Ming Chou
- Center for Prevention and Therapy of Gynecological Cancers, Department of Research, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan, ROC
| | - Tang-Yuan Chu
- Center for Prevention and Therapy of Gynecological Cancers, Department of Research, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan, ROC.,Department of Obstetrics & Gynecology, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan, ROC.,Department of Life Science, Tzu Chi University, Hualien 970, Taiwan, ROC
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8
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Sørensen TT, Farkas DK, Riahi EZB, Ehrenstein V, Henderson VW. Motor Neuron Disease and Risk of Cancer: A Population-Based Cohort Study in Denmark. Clin Epidemiol 2020; 12:1347-1353. [PMID: 33324108 PMCID: PMC7733394 DOI: 10.2147/clep.s271543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 10/27/2020] [Indexed: 11/23/2022] Open
Abstract
Background Some neurogenerative diseases have been linked to a reduced risk of cancer, but the association between motor neuron disease and cancer risk is not well understood. We hypothesized that cancer risk would be lower among those with motor neuron disease and its most common subtype, amyotrophic lateral sclerosis. Methods We conducted a population-based cohort study of motor neuron disease and cancer risk using routinely collected data from population-based registries in Denmark. We examined cancer incidence among patients diagnosed with motor neuron disease between January 1980 and December 2013 followed through 2013. Using Danish national cancer rates for the study period, we computed standardized incidence ratios as a measure of relative risks. Results In the cohort of 5053 patients with a motor neuron disease, the overall standardized incidence ratio of any cancer was 1.17 (95% confidence interval [CI], 1.03-1.31); the corresponding standardized incidence ratio for amyotrophic lateral sclerosis was 1.24 (95% CI, 0.96-1.57). The standardized incidence ratios of any cancer in the cohort with motor neuron disease was 1.52 (95% CI, 1.22-1.87) for <1 year of follow-up; 0.87 (95% CI, 0.68-1.09) for years 1-5 of follow-up; and 1.22 (95% CI, 1.01-1.46) for >5 years of follow-up. Beyond one year of follow-up, patients in the motor neuron disease had elevated standardized incidence ratios for lymphoid leukemia, non-Hodgkin lymphoma, and basal cell skin cancer. Conclusion Findings fail to support the hypothesis that motor neuron disease or amyotrophic lateral sclerosis is associated with reduced cancer incidence. An elevated risk of cancer during the first year of follow-up may be attributable to heightened surveillance.
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Affiliation(s)
| | | | | | - Vera Ehrenstein
- Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark
| | - Victor W Henderson
- Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.,Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA.,Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA
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Vasaitis L, Nordmark G, Theander E, Backlin C, Smedby KE, Askling J, Rönnblom L, Sundström C, Baecklund E. Population-based study of patients with primary Sjögren's syndrome and lymphoma: lymphoma subtypes, clinical characteristics, and gender differences. Scand J Rheumatol 2020; 49:225-232. [PMID: 32153241 DOI: 10.1080/03009742.2019.1696403] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Objective: To examine lymphoma subtypes, clinical characteristics, and gender differences in patients with primary Sjögren's syndrome (pSS) and lymphoma in a population-based setting.Method: Patients with Sjögren's syndrome and lymphoma diagnoses were identified by linkage of the Swedish Patient Register 1964-2007 with the Cancer Register 1990-2007. Clinical data were collected from medical records and lymphoma tissues were re-examined. The lymphoma subtype distribution was compared with the Swedish Lymphoma Register.Results: We identified 105 pSS patients with lymphoma. Diffuse large B-cell lymphoma (DLBCL) (32%) and marginal zone lymphoma [MZL including mucosa-associated lymphoid tissue (MALT) lymphoma] (31%) were the most common lymphoma subtypes. The proportion of DLBCL was not increased compared to the general population reference (32%, p = 1), in contrast to MZL (general population 5%, p < 0.0001). Compared to DLBCL, MALT lymphoma was diagnosed at a younger age (55 vs 67 years, p = 0.0001), and earlier after patient-reported sicca onset (7 vs 18 years, p = 0.0001) and pSS diagnosis (2 vs 9 years, p = 0.0005). Sixteen of the pSS-lymphoma cases were men (15%), twice the proportion in general pSS populations. Compared to women, men had a shorter median time from pSS diagnosis to lymphoma diagnosis (1 vs 8 years, p = 0.0003) and more often had lymphoma in the salivary glands (56% vs 29%, p = 0.04).Conclusion: DLBCL and MZL are common in pSS patients, but only MZL/MALT lymphoma occurs at an increased relative frequency in pSS compared to the general population. The study supports increased awareness of signs of lymphoma in men in the first years after pSS diagnosis.
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Affiliation(s)
- L Vasaitis
- Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden
| | - G Nordmark
- Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden
| | - E Theander
- Department of Rheumatology, Skåne University Hospital, Lund University, Malmö, Sweden
| | - C Backlin
- Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden
| | - K E Smedby
- Department of Medical Sciences, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden
| | - J Askling
- Department of Medical Sciences, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden
| | - L Rönnblom
- Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden
| | - C Sundström
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
| | - E Baecklund
- Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden
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10
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Skarlis C, Argyriou E, Mavragani CP. Lymphoma in Sjögren’s Syndrome: Predictors and Therapeutic Options. CURRENT TREATMENT OPTIONS IN RHEUMATOLOGY 2020. [DOI: 10.1007/s40674-020-00138-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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11
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Kapsogeorgou EK, Voulgarelis M, Tzioufas AG. Predictive markers of lymphomagenesis in Sjögren's syndrome: From clinical data to molecular stratification. J Autoimmun 2019; 104:102316. [PMID: 31431317 DOI: 10.1016/j.jaut.2019.102316] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 08/03/2019] [Indexed: 12/26/2022]
Abstract
Sjögren's syndrome (SS) is a chronic systemic autoimmune disease, affecting predominantly the exocrine glands, a large array of systemic manifestations and high risk of lymphoma development. The latter constitutes the major adverse outcome of SS contributing in the increased morbidity and mortality of the disease. The vast majority of lymphomas in SS are B-cell non-Hodgkin's lymphomas (NHL), primarily indolent mucosa-associated lymphoid tissue (MALT) lymphomas, followed by nodal marginal zone lymphomas (NMZL) and diffuse large B cell lymphomas (DLBCL). In the last 3 decades and due to the adverse impact of NHL in disease outcome, an effort has been undertaken to identify markers and models predicting patients with SS at high risk for lymphoma development. Several epidemiological, clinical, laboratory and histological parameters, some of which are evident at the time of SS diagnosis, were proved to independently predict the development of NHL. These include salivary gland enlargement, skin vasculitis/purpura, glomerulonephritis, peripheral neuropathy, Raynaud's phenomenon, lymphadenopathy, splenomegaly, cytopenias, hypocomplementemia, cryoglobulinemia, rheumatoid factor, anti-Ro/La autoantibodies, hypergammaglobulinemia, serum monoclonal gammopathy, biopsy focus score and organization of lymphocytic infiltrates in the salivary glands into ectopic germinal centers. Prediction models combining some of the afore-mentioned predictors have also been described. However, the identification of specific and sensitive molecular biomarkers, related to the process of lymphomagenesis is still pending. Recently, we described a novel biomarker the miR200b-5p micro-RNA. Low levels of this miRNA in the minor salivary glands, appears to discriminate with high specificity and sensitivity the SS patients who have from those who do not have NHL. miR200b-5p, being expressed years before the clinical onset of NHL, independently predicts NHL development with a predictive value higher than the previously published multifactorial models and has a possible role in the monitoring of therapeutic response. Thus, it is a strong candidate for the identification and follow-up of patients at risk.
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Affiliation(s)
- Efstathia K Kapsogeorgou
- Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Greece; Academic Joint Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, Greece.
| | - Michael Voulgarelis
- Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Greece; Academic Joint Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, Greece.
| | - Athanasios G Tzioufas
- Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Greece; Academic Joint Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, Greece.
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12
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Mörth C, Valachis A, Abu Sabaa A, Marshall K, Hedström G, Flogegård M, Baecklund E, Enblad G. Autoimmune disease in patients with diffuse large B-cell lymphoma: occurrence and impact on outcome. Acta Oncol 2019; 58:1170-1177. [PMID: 31131659 DOI: 10.1080/0284186x.2019.1619936] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Background: Patients with certain autoimmune diseases (AID) have an increased risk of developing diffuse large B-cell lymphoma (DLBCL). However, the occurrence of AID in patients with DLBCL as well as the impact of AID on outcome has not been extensively studied. The main purpose of this study was to establish the occurrence of AIDs in a population-based cohort of DLBCL patients and to compare outcomes in patients with or without AID treated with rituximab(R)-CHOP/CHOP-like treatment. We also aimed to analyse gender differences and the potential role of different AIDs on outcome and the frequency of treatment-associated neutropenic fever. Patients and methods: All adult patients treated 2000-2013 with R-CHOP/CHOP-like treatment for DLBCL in four counties of Sweden were included (n = 612). Lymphoma characteristics, outcome and the presence of AID were obtained through medical records. Results: The number of patients with AID was 106 (17.3%). Thyroid disease dominated (n = 33, 31.1%) followed by rheumatoid arthritis (RA) (n = 24, 22.6%). The proportion of AID was significantly higher in females (59/254, 23.2%) vs. in males (47/358, 13.1%) (p = .001). In the whole cohort there was no difference in event free survival (EFS) or overall survival (OS) between patients with or without AID. However, patients with an AID primarily mediated by B-cell responses (thyroid disorders excluded) had a worse OS (p = .037), which seemed to affect only women. The AID group more often had neutropenic fever after first treatment (16.0% vs 8.7%, p = .034) and those with neutropenic fever had a worse OS (p = .026) in Kaplan-Meier analyses. Conclusion: There is a high prevalence of AID among patients with DLBCL. AIDs categorized as primarily B-cell mediated (in this study mainly RA, systemic lupus erythematosus and Sjögren's syndrome) may be associated with inferior OS. AID patients may be more prone to neutropenic fever compared to patients without concomitant AID.
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Affiliation(s)
- Charlott Mörth
- Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden
- Experimental and Clinical Oncology, Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden
| | - Antonios Valachis
- Department of Oncology, Faculty of Medicine and health, Örebro University, Örebro, Sweden
| | - Amal Abu Sabaa
- Experimental and Clinical Oncology, Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden
| | - Katharina Marshall
- Experimental and Clinical Oncology, Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden
| | - Gustaf Hedström
- Experimental and Clinical Oncology, Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden
| | - Max Flogegård
- Department of Internal Medicine, Falun General Hospital, Falun, Sweden
| | - Eva Baecklund
- Section of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Gunilla Enblad
- Experimental and Clinical Oncology, Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden
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13
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Retamozo S, Brito-Zerón P, Ramos-Casals M. Prognostic markers of lymphoma development in primary Sjögren syndrome. Lupus 2019; 28:923-936. [PMID: 31215845 DOI: 10.1177/0961203319857132] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Sjögren syndrome is a systemic autoimmune disease that principally affects women between the fourth and sixth decades of life who present with sicca symptomatology caused by dryness of the main mucosal surfaces. The clinical spectrum of Sjögren syndrome extends from dryness to systemic involvement. Since 1978, Sjögren syndrome has been closely associated with an enhanced risk of lymphoma, one of the most severe complications a patient may develop. Primary Sjögren syndrome patients have a 10-44-fold greater risk of lymphoma than healthy individuals, higher than that reported for systemic lupus erythematosus and rheumatoid arthritis. The close link between lymphoma and Sjögren syndrome is clearly exemplified by the very specific type of lymphoma arising in Sjögren syndrome patients, mainly low-grade B-cell lymphomas (predominantly a marginal zone histological type) with primary extranodal involvement of the major salivary glands (overwhelmingly parotid), with a primordial role of cryoglobulinemic-related markers (both clinical and immunological). The most recent studies support a higher number of risk factors detected in an individual leads to a higher lymphoma risk. A close follow-up of high-risk groups with longitudinal assessments of all known risk factors, including cryoglobulin-related markers and EULAR Sjögren's syndrome disease activity index measurement in particular, is mandatory.
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Affiliation(s)
- S Retamozo
- 1 Instituto de Investigaciones en Ciencias de la Salud (INICSA), Universidad Nacional de Córdoba (UNC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, Argentina.,2 Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Córdoba, Argentina.,3 Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Barcelona, Spain
| | - P Brito-Zerón
- 3 Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Barcelona, Spain.,4 Department of Medicine, Hospital CIMA-Sanitas, Barcelona, Spain
| | - M Ramos-Casals
- 3 Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Barcelona, Spain.,5 Department of Autoimmune Diseases, ICMiD, Barcelona, Spain.,6 Department of Medicine, University of Barcelona, Barcelona, Spain
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14
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Kane E, Painter D, Smith A, Crouch S, Oliver S, Patmore R, Roman E. The impact of rheumatological disorders on lymphomas and myeloma: a report on risk and survival from the UK's population-based Haematological Malignancy Research Network. Cancer Epidemiol 2019; 59:236-243. [PMID: 30844679 PMCID: PMC6452783 DOI: 10.1016/j.canep.2019.02.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Revised: 02/05/2019] [Accepted: 02/09/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND Autoimmune inflammatory disease increases the risk of diffuse large B-cell lymphoma (DLBCL) and marginal zone lymphoma (MZL), but findings for other mature B-cell malignancies are equivocal. Furthermore, it has been suggested that the increase in DLBCL is due to the activated B-cell (ABC) subtype; but data on this, and the impact of inflammatory co-morbidities on survival, are sparse and contradictory. METHODS Data are from an established UK population-based cohort. Patients (n = 6834) diagnosed between 01/2009 and 08/2015 are included; DLBCL (n = 1771), myeloma (n = 1760), chronic lymphocytic leukaemia (CLL, n = 1580), MZL (n = 936), and follicular lymphoma (FL, n = 787). Information on rheumatological disorders and deaths was obtained by record-linkage to nationally compiled Hospital Episode Statistics, with age-and sex-matched individuals (n = 68,340) from the same catchment population (˜4 million people) providing the comparator. RESULTS Significantly increased risks for DLBCL (OR = 2.3, 95% CI 1.8-2.8) and MZL (OR = 2.0, 95% CI 1.5-2.7) were found for those with rheumatological disorders; the site distribution of those with/without rheumatological conditions differing for DLBCL (p = 0.007) and MZL (p = 0.002). No increases in risk were observed for the remaining mature B-cell malignancies, and no associations with survival were detected for DLBCL (age-adjusted HR = 1.2, 95% CI 0.9-1.6) or MZL (age-adjusted HR = 1.0, 95% CI 0.6-1.9). Furthermore, whilst our findings provide evidence for an association with rheumatological disease severity for DLBCL, they offer little support for the notion that the association is driven by an increase in the incidence of the ABC subtype. CONCLUSION Our findings support the hypothesis that the chronic activation and proliferation of specific B-cell populations which characterize autoimmune disease increase the potential for the lymphomagenic events that lead to DLBCL and MZL in both males and females; but have no impact on the development of CLL, FL or MM, or on survival.
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MESH Headings
- Aged
- Aged, 80 and over
- Female
- Humans
- Leukemia, Lymphocytic, Chronic, B-Cell
- Lymphoma/epidemiology
- Lymphoma/mortality
- Lymphoma/pathology
- Lymphoma, B-Cell, Marginal Zone/epidemiology
- Lymphoma, B-Cell, Marginal Zone/mortality
- Lymphoma, Follicular/epidemiology
- Lymphoma, Follicular/mortality
- Lymphoma, Follicular/pathology
- Lymphoma, Large B-Cell, Diffuse/epidemiology
- Lymphoma, Large B-Cell, Diffuse/mortality
- Lymphoma, Large B-Cell, Diffuse/pathology
- Male
- Middle Aged
- Multiple Myeloma/epidemiology
- Multiple Myeloma/mortality
- Multiple Myeloma/pathology
- Rheumatic Diseases/epidemiology
- Rheumatic Diseases/mortality
- Rheumatic Diseases/pathology
- United Kingdom/epidemiology
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Affiliation(s)
- Eleanor Kane
- Department of Health Sciences, University of York, York, UK.
| | - Daniel Painter
- Department of Health Sciences, University of York, York, UK
| | | | - Simon Crouch
- Department of Health Sciences, University of York, York, UK
| | - Steven Oliver
- Department of Health Sciences, University of York, York, UK; Hull York Medical School, York, UK
| | | | - Eve Roman
- Department of Health Sciences, University of York, York, UK
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15
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Tanaka S, Sawada N, Yamaji T, Shimazu T, Goto A, Iwasaki M, Inoue M, Tsugane S. Female reproductive factors and risk of lymphoid neoplasm: The Japan Public Health Center-based Prospective Study. Cancer Sci 2019; 110:1442-1452. [PMID: 30719848 PMCID: PMC6447856 DOI: 10.1111/cas.13962] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Revised: 01/28/2019] [Accepted: 01/30/2019] [Indexed: 12/21/2022] Open
Abstract
Although a possible role of reproductive factors in lymphomagenesis has been hypothesized, results of epidemiological studies have been inconsistent. Here, we investigated the association between reproductive factors and the risk of lymphoid neoplasm and its subgroups. We used data from a large‐scale, population‐based prospective study in a Japanese cohort with 42 691 eligible women aged 40‐69 years from 1990 to 1994. During a mean follow up of 18.7 years, we identified 176 cases of lymphoid neoplasm and 90 of non‐Hodgkin lymphoma (NHL). A multivariable‐adjusted Cox proportional hazards regression model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the risk of lymphoid neoplasms and its subgroups according to self‐reported reproductive factors. Parous women had an increased risk of lymphoid neoplasm compared with nulliparous women (HR = 2.51, 95% CI, 1.03‐6.13). An increased risk of lymphoid neoplasms was found in women with later onset of menarche (≤13 years old; reference: 14‐15; HR = 1.75, 95% CI = 1.10‐2.79: ≥16; HR = 1.93, 95% CI = 1.17‐3.19: P‐trend: 0.01) and a shorter menstrual cycle (28‐29 days; reference: ≤27; HR = 1.60, 95% CI = 1.05‐2.43, P‐trend = 0.81). No association was observed between lymphoid neoplasms and other reproductive factors, including age at first birth, breastfeeding, type of menopause, or exogenous hormone use. Our study suggests that ever parity, late age at menarche and a short menstrual cycle length may be associated with the development of lymphoid neoplasms. The inconsistency seen in epidemiological research to date warrants further investigation.
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Affiliation(s)
- Shiori Tanaka
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.,Department of Global Health Policy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Norie Sawada
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Taiki Yamaji
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Taichi Shimazu
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Atsushi Goto
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Motoki Iwasaki
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Manami Inoue
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Shoichiro Tsugane
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
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16
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Sène D, Ismael S, Forien M, Charlotte F, Kaci R, Cacoub P, Diallo A, Dieudé P, Lioté F. Ectopic Germinal Center-Like Structures in Minor Salivary Gland Biopsy Tissue Predict Lymphoma Occurrence in Patients With Primary Sjögren's Syndrome. Arthritis Rheumatol 2018; 70:1481-1488. [PMID: 29669392 DOI: 10.1002/art.40528] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2017] [Accepted: 04/10/2018] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To determine risk factors for primary Sjögren's syndrome (SS)-associated lymphoma in a multicenter cohort of patients, with analysis of the predictive power of previously reported risk factors, including the presence of ectopic germinal center (GC)-like structures in minor salivary gland (MSG) biopsy tissue. METHODS One hundred fifteen patients with primary SS were included, and MSG biopsy tissue from these patients was retrospectively examined, focusing on the presence of ectopic GC-like structures. Epidemiologic, clinical, biologic, immunologic, and histologic data were collected at the time of diagnosis of primary SS. Patients with non-Hodgkin's lymphoma (NHL) were compared with those without NHL during the follow-up period, using a Cox proportional hazards multiple regression model. RESULTS NHL was diagnosed in 8 patients (6.96%), and ectopic GC-like structures in 19 patients (16.5%). The presence of ectopic GC-like structures was associated with a 7.8-fold increased risk of lymphoma occurrence (95% confidence interval [95% CI] 1.73-34.86 [P = 0.0075]). Other independent predictors included a positive cryoglobulin test result (hazard ratio [HR] 7.10, 95% CI 1.74-28.92 [P = 0.006]), male sex (HR 28.73, 95% CI 4.46-144.87 [P = 0.0004]), sensorimotor neuropathy (HR 35.48, 95% CI 5.79-217.39 [P = 0.0001]), and splenomegaly (HR 19.9, 95% CI 4.4-90 [P = 0.0001]). CONCLUSION The presence of ectopic GC-like structures in MSG biopsy tissue is associated with the risk of lymphoma in patients with primary SS. These data reinforce the major role of MSG biopsy tissue in primary SS, for the identification a priori of a subgroup of patients with the highest risk of lymphoma.
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Affiliation(s)
- Damien Sène
- Lariboisière Fernand Widal Hospital, AP-HP and Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Sophie Ismael
- Lariboisière Fernand Widal Hospital, AP-HP and Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Marine Forien
- Bichat Hospital, AP-HP and Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Frédéric Charlotte
- Pitié-Salpêtrière Hospital, AP-HP and Pierre & Marie Curie University, Paris, France
| | - Rachid Kaci
- Lariboisière Fernand Widal Hospital, AP-HP, Paris, France
| | - Patrice Cacoub
- Pitié-Salpêtrière Hospital, AP-HP and Pierre & Marie Curie University, Paris, France
| | - Abdourahmane Diallo
- Biostatistics and Clinical Trial Unit, Lariboisière Fernand Widal Hospital, AP-HP, Paris, France
| | - Philippe Dieudé
- Bichat Hospital, AP-HP and Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Frédéric Lioté
- INSERM UMR 1132, Lariboisière Fernand Widal Hospital, AP-HP, and Université Paris Diderot, Sorbonne Paris Cité, Paris, France
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17
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Molecular Highlighting Analysis of Mutational P27 Gene Products in Association with Human T-lymphotropic (HTLV-1) Infection in Tissues from Iraqi Patients with Non-Hodgkin’s lymphoma. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2017. [DOI: 10.22207/jpam.11.3.24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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18
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Ramírez Sepúlveda JI, Kvarnström M, Eriksson P, Mandl T, Norheim KB, Johnsen SJ, Hammenfors D, Jonsson MV, Skarstein K, Brun JG, Rönnblom L, Forsblad-d'Elia H, Magnusson Bucher S, Baecklund E, Theander E, Omdal R, Jonsson R, Nordmark G, Wahren-Herlenius M. Long-term follow-up in primary Sjögren's syndrome reveals differences in clinical presentation between female and male patients. Biol Sex Differ 2017; 8:25. [PMID: 28789696 PMCID: PMC5549313 DOI: 10.1186/s13293-017-0146-6] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2017] [Accepted: 07/26/2017] [Indexed: 12/28/2022] Open
Abstract
Background Despite men being less prone to develop autoimmune diseases, male sex has been associated with a more severe disease course in several systemic autoimmune diseases. In the present study, we aimed to investigate differences in the clinical presentation of primary Sjögren’s syndrome (pSS) between the sexes and establish whether male sex is associated with a more severe form of long-term pSS. Methods Our study population included 967 patients with pSS (899 females and 68 males) from Scandinavian clinical centers. The mean follow-up time (years) was 8.8 ± 7.6 for women and 8.5 ± 6.2 for men (ns). Clinical data including serological and hematological parameters and glandular and extraglandular manifestations were compared between men and women. Results Male patient serology was characterized by more frequent positivity for anti-Ro/SSA and anti-La/SSB (p = 0.02), and ANA (p = 0.02). Further, men with pSS were more frequently diagnosed with interstitial lung disease (p = 0.008), lymphadenopathy (p = 0.04) and lymphoma (p = 0.007). Conversely, concomitant hypothyroidism was more common among female patients (p = 0.009). Conclusions We observe enhanced serological responses and higher frequencies of lymphoma-related extraglandular manifestations in men with pSS. Notably, lymphoma itself was also significantly more common in men. These observations may reflect an aggravated immune activation and a more severe pathophysiological state in male patients with pSS and indicate a personalized managing of the disease due to the influence of the sex of patients with pSS.
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Affiliation(s)
- Jorge I Ramírez Sepúlveda
- Unit of Experimental Rheumatology, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, SE-171 76, Stockholm, Sweden
| | - Marika Kvarnström
- Unit of Experimental Rheumatology, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, SE-171 76, Stockholm, Sweden
| | - Per Eriksson
- Division of Rheumatology, Department of Clinical Experimental Medicine, Linköping University, Linköping, Sweden
| | - Thomas Mandl
- Department of Rheumatology, Skåne University Hospital, Malmö, Sweden
| | - Katrine Brække Norheim
- Clinical immunology unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway
| | - Svein Joar Johnsen
- Clinical immunology unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway
| | - Daniel Hammenfors
- Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.,Department of Rheumatology, Haukeland University Hospital, Bergen, Norway
| | - Malin V Jonsson
- Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.,Section for Oral and Maxillofacial Radiology, Department of Clinical Dentistry, University of Bergen, Bergen, Norway
| | - Kathrine Skarstein
- Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.,Department of Pathology, Haukeland University Hospital, Bergen, Norway
| | - Johan G Brun
- Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.,Department of Rheumatology, Haukeland University Hospital, Bergen, Norway
| | | | - Lars Rönnblom
- Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | - Helena Forsblad-d'Elia
- Department of Public Health and Clinical Medicine, Rheumatology, Umeå University, Umeå, Sweden
| | - Sara Magnusson Bucher
- Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Eva Baecklund
- Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | - Elke Theander
- Department of Rheumatology, Skåne University Hospital, Malmö, Sweden
| | - Roald Omdal
- Clinical immunology unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway
| | - Roland Jonsson
- Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.,Department of Rheumatology, Haukeland University Hospital, Bergen, Norway
| | - Gunnel Nordmark
- Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | - Marie Wahren-Herlenius
- Unit of Experimental Rheumatology, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, SE-171 76, Stockholm, Sweden.
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Beheshti A, Neuberg D, McDonald JT, Vanderburg CR, Evens AM. The Impact of Age and Sex in DLBCL: Systems Biology Analyses Identify Distinct Molecular Changes and Signaling Networks. Cancer Inform 2015; 14:141-8. [PMID: 26691437 PMCID: PMC4676434 DOI: 10.4137/cin.s34144] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2015] [Revised: 10/19/2015] [Accepted: 10/24/2015] [Indexed: 12/16/2022] Open
Abstract
Potential molecular alterations based on age and sex are not well defined in diffuse large B-cell lymphoma (DLBCL). We examined global transcriptome DLBCL data from The Cancer Genome Atlas (TCGA) via a systems biology approach to determine the molecular differences associated with age and sex. Collectively, sex and age revealed striking transcriptional differences with older age associated with decreased metabolism and telomere functions and female sex was associated with decreased interferon signaling, transcription, cell cycle, and PD-1 signaling. We discovered that the key genes for most groups strongly regulated immune function activity. Furthermore, older females were predicted to have less DLBCL progression versus older males and young females. Finally, analyses in systems biology revealed that JUN and CYCS signaling were the most critical factors associated with tumor progression in older and male patients. We identified important molecular perturbations in DLBCL that were strongly associated with age and sex and were predicted to strongly influence tumor progression.
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Affiliation(s)
- Afshin Beheshti
- Division of Hematology/Oncology, Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA, USA
| | - Donna Neuberg
- Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard University, Boston, MA, USA
| | | | | | - Andrew M Evens
- Director, Tufts Cancer Center, and Chief, Division of Hematology/Oncology, Tufts Medical Center, Boston, MA, USA. ; Professor of Medicine, Tufts University School of Medicine, Boston, MA, USA
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Brandt JE, Priori R, Valesini G, Fairweather D. Sex differences in Sjögren's syndrome: a comprehensive review of immune mechanisms. Biol Sex Differ 2015; 6:19. [PMID: 26535108 PMCID: PMC4630965 DOI: 10.1186/s13293-015-0037-7] [Citation(s) in RCA: 73] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Accepted: 09/17/2015] [Indexed: 02/03/2023] Open
Abstract
Autoimmune diseases (ADs) are estimated to affect between 5 and 8 % of the US population, and approximately 80 % of these patients are women. Sjögren’s syndrome (SS) is an AD that occurs predominately in women over men (16:1). The hallmark characteristic of SS is diminished secretory production from the primary exocrine gland and the lacrimal or salivary glands resulting in symptoms of dry eye and mouth. The disease is believed to be mediated by an inflammatory and autoantibody response directed against salivary and lacrimal gland tissues. This review will examine the literature on sex differences in the immune response of patients and animal models of Sjögren’s syndrome in order to gain a better understanding of disease pathogenesis.
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Affiliation(s)
- Jessica E Brandt
- Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205 USA ; Reumatologia, Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, 00161 Rome, Italy
| | - Roberta Priori
- Reumatologia, Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, 00161 Rome, Italy
| | - Guido Valesini
- Reumatologia, Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, 00161 Rome, Italy
| | - DeLisa Fairweather
- Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205 USA ; Department of Cardiovascular Diseases, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224 USA
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Horesh N, Horowitz NA. Does gender matter in non-hodgkin lymphoma? Differences in epidemiology, clinical behavior, and therapy. Rambam Maimonides Med J 2014; 5:e0038. [PMID: 25386354 PMCID: PMC4222427 DOI: 10.5041/rmmj.10172] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Non-Hodgkin lymphoma (NHL) is one of the most common hematologic malignancies worldwide. The incidence of NHL has been rising for several decades; however, in the last 20 years, it reached a plateau. NHL incidence among males is significantly higher than in females. In addition to gender itself, gravidity has a protective role against NHL occurrence. Gender also matters in terms of NHL clinical characteristics. For example, female predominance was found in three extra-nodal sites (the breast, thyroid, and the respiratory system) occasionally involved in NHL. The diagnosis of NHL during pregnancy is associated with a unique clinical behavior. It is usually diagnosed in the second or third trimester and in advanced stage. Furthermore, the histological subtype is highly aggressive, and reproductive organ involvement is common. The reduced rate of NHL among females may be explained by direct effects of estrogens on lymphoma cell proliferation or by its effect on anti-tumor immune response. Gender has an important role in responsiveness to standard B cell NHL treatment. Among older adults, women benefited more from the addition of the anti-CD20 antibody rituximab to standard chemotherapy regimens. This phenomenon can be explained by the difference in clearance rate of rituximab that was found to be significantly lower among older females than older males. In mantle cell lymphoma, women receiving lenalidomide have higher rates of response. An understanding of the mechanisms responsible for gender-associated NHL differences will ultimately improve the clinical approach, allowing for a more accurate assessment of prognosis and patient-tailored treatment.
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Affiliation(s)
- Nurit Horesh
- Department of Internal Medicine H, Rambam Health Care Campus, Haifa, Israel
| | - Netanel A Horowitz
- Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel ; Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
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22
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Reksten TR, Jonsson MV. Sjögren's syndrome: an update on epidemiology and current insights on pathophysiology. Oral Maxillofac Surg Clin North Am 2014; 26:1-12. [PMID: 24287189 DOI: 10.1016/j.coms.2013.09.002] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Primary Sjögren's syndrome (pSS) is an autoimmune chronic inflammatory disorder affecting 0.2% to 3.0% of the population, with a 9:1 female to male ratio. Features are oral and ocular dryness, local and systemic autoantibody production, and progressive focal mononuclear cell infiltration in the affected salivary and lacrimal glands. Lymphoma is the most severe complication of pSS, occurring in 4% to 5% of patients. Genetic studies identified an association with HLA and susceptibility genes in cytokine genes and genes involved in B-cell differentiation. Genetic variations may help explain why disease manifestations differ among patients and supports the hypothesis of certain distinct disease phenotypes.
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Affiliation(s)
- Tove R Reksten
- Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, The Laboratory Building, 5th Floor, Haukeland University Hospital, Bergen N-5021, Norway
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23
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Costas L, de Sanjosé S, Infante-Rivard C. Reproductive factors and non-Hodgkin lymphoma: a systematic review. Crit Rev Oncol Hematol 2014; 92:181-93. [PMID: 25132165 DOI: 10.1016/j.critrevonc.2014.07.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2013] [Revised: 05/08/2014] [Accepted: 07/23/2014] [Indexed: 02/07/2023] Open
Abstract
Considerable efforts have been made to elucidate non-Hodgkin lymphoma's (NHL) etiology during the last decades. Some evidence points to an association with reproductive factors, as incidence rates for most NHL subtypes are usually higher in men than in women, and several subtypes express hormonal receptors. Although the evidence is not compelling, some studies show an inverse association with gravidity. Associations with postmenopausal hormone therapy are usually derived from unopposed estrogen use, rather than for the combination of estrogen with progestin, but these findings vary by study design. Inconsistencies in the results are likely due to the complex relationship between reproductive, biological, and sociodemographic factors, as well as to study limitations. Elucidating the role of hormonal factors should provide clues for therapeutic options and public health decisions. We provide an overview of the available evidence on reproductive factors in NHL etiology, underscoring potential sources of discrepancies and bias.
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Affiliation(s)
- Laura Costas
- Unit of Infections and Cancer, Cancer Epidemiology Research Programme, IDIBELL, Catalan Institute of Oncology, Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain; CIBER Epidemiologia y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, Montreal, Canada.
| | - Silvia de Sanjosé
- Unit of Infections and Cancer, Cancer Epidemiology Research Programme, IDIBELL, Catalan Institute of Oncology, Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain; CIBER Epidemiologia y Salud Pública (CIBERESP), Madrid, Spain
| | - Claire Infante-Rivard
- Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, Montreal, Canada
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Abstract
Non-Hodgkin Lymphoma (NHL) occurs worldwide although there is notable geographical variation in incidence and subtype distribution. These differences are due to a combination of demographic, environmental and other unidentified factors. A dramatic increase in NHL incidence was seen starting around 1970, with subsequent stabilization 10 years ago. Despite this plateau, the number of new cases in many countries will increase significantly in coming years due primarily to aging populations. In the majority of cases, strong risk factors are not identifiable. There is significant epidemiological heterogeneity between NHL subtypes, yet cancer registries have tended to consider NHL as a single entity. This is one of several epidemiological obstacles discussed.
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Affiliation(s)
- Pamela Skrabek
- Department of Medical Oncology and Haematology, CancerCare Manitoba, Canada; Department of Community Health Sciences, University of Manitoba, Canada.
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25
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Nguyen CQ, Peck AB. The Interferon-Signature of Sjögren's Syndrome: How Unique Biomarkers Can Identify Underlying Inflammatory and Immunopathological Mechanisms of Specific Diseases. Front Immunol 2013; 4:142. [PMID: 23847613 PMCID: PMC3701867 DOI: 10.3389/fimmu.2013.00142] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2013] [Accepted: 05/27/2013] [Indexed: 11/13/2022] Open
Abstract
Innate immune responses direct the nature and specificity of downstream adaptive responses in autoimmune diseases. One of the strongest markers of innate immunity is the up-regulated expression of interferon (IFN) and IFN-responsive/stimulated genes (IRGs/ISGs). While multiple IRGs are induced during the innate phase of host responses, transcriptome data suggest unique IRG-signatures for different diseases. Sjögren's syndrome (SjS) is characterized by chronic immune attacks against exocrine glands leading to exocrine dysfunction, plus strong up-regulated expressions of IFN IRG transcripts. Genome-wide transcriptome analyses indicate that differentially expressed IRGs are restricted during disease development and therefore define underlying etiopathological mechanisms. Here we review the innate immune-associated IFN-signature of SjS and show how differential gene expressions of IRG/ISG sets interact molecularly and biologically to identify critical details of SjS etiopathogenesis.
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Affiliation(s)
- Cuong Quoc Nguyen
- Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida , Gainesville, FL , USA ; Center for Orphaned Autoimmune Diseases, University of Florida , Gainesville, FL , USA
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26
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Tarella C, Gueli A, Ruella M, Cignetti A. Lymphocyte transformation and autoimmune disorders. Autoimmun Rev 2013; 12:802-13. [DOI: 10.1016/j.autrev.2012.11.004] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Peck AB, Nguyen CQ. Transcriptome analysis of the interferon-signature defining the autoimmune process of Sjögren's syndrome. Scand J Immunol 2012; 76:237-45. [PMID: 22703193 DOI: 10.1111/j.1365-3083.2012.02749.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Sjögren's syndrome (SS) of humans and SS-like (SjS-like) diseases in mouse models are characterized by chronic immune attacks against the salivary and lacrimal glands leading to exocrine dysfunction. One characteristic of SS and SjS-like diseases repeatedly observed is a strong upregulated expression of both the type I (α/β) and type II (γ) interferons (IFNs). In addition, recent global transcriptome studies have identified a variety of IFN-stimulated gene (ISG) transcripts differentially expressed in tissues of SS patients and mouse models exhibiting SjS-like disease. Analyses of these transcriptome databases indicate that the sets of differentially expressed genes are highly restricted, suggesting that there is a unique specificity in ISGs activated (or suppressed) during development and onset of disease. As a result, these observations have led to both SS and SjS-like diseases being designated as 'interferon-signature' diseases. While SS and SjS-like diseases may be designated as such, very little effort has been made to determine what an interferon-signature might signify relative to autoinflammation and whether it might point directly to an underlying etiopathological mechanism. Here, we review these limited data and provide a model of how the products of these genes interact molecularly and biologically to define critical details of SS pathology.
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Affiliation(s)
- A B Peck
- Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA. peck@ pathology.ufl.edu
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28
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Jonsson MV, Theander E, Jonsson R. Predictors for the development of non-Hodgkin lymphoma in primary Sjögren's syndrome. Presse Med 2012; 41:e511-6. [PMID: 22867948 DOI: 10.1016/j.lpm.2012.05.025] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2012] [Revised: 05/28/2012] [Accepted: 05/30/2012] [Indexed: 11/26/2022] Open
Abstract
Sjögren's syndrome (SS) is a complex autoimmune disease with multi-organ involvement. Its most serious complication is the development of non-Hodgkin lymphoma (NHL). In cohorts of unselected patients with long observation, this lifetime risk is estimated to be 5 to 15%, or approximately 20 times increased risk compared to the general population. Being able to identify patients prone to malignancy would significantly aid in the process of customised treatment and strategy for follow-up. Among the established predictors for lymphoma development in SS, we recognize recurrent or permanent swelling of major salivary glands (SG), lymphadenopathy, cryoglobulinemia, splenomegaly, low complement levels of C4 and C3, lymphopenia, skin vasculitis or palpable purpura, M-component in serum or urine, peripheral neuropathy, glomerulonephritis and elevated beta2-microglobulin. More recent suggestions include some genetic factors, CD4 lymphocytopenia, and ectopic germinal center-like structures in minor SG biopsies. Despite these predictors, there remains a need for defining algorithms for NHL screening and patient follow-up in SS.
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Affiliation(s)
- Malin V Jonsson
- University of Bergen, Department of Clinical Dentistry - Section for Oral and Maxillofacial Radiology, Bergen, Norway
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29
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Lindqvist CA, Loskog ASI. T regulatory cells in B-cell malignancy - tumour support or kiss of death? Immunology 2012; 135:255-60. [PMID: 22112044 DOI: 10.1111/j.1365-2567.2011.03539.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
It is well established that T regulatory (Treg) cells counteract tumour immunity. However, conflicting results describing the role of Treg cells in haematological tumours warrant further investigations to clarify the interactions between Treg cells and the tumour. B-cell malignancy derives from different stages of B-cell development and differentiation in which T cells play a profound role. The transformed B cell may still be in need of T-cell help to thrive but simultaneously they may be recognized and destroyed by cytotoxic lymphocytes. Recent reports demonstrate that Treg cells can suppress and even kill B cells as part of their normal function to rescue the body from autoimmunity. An emerging body of evidence points out that Treg cells not only inhibit tumour-specific T cells but may also have a role in suppressing the progression of the B-cell tumour. In this review, we discuss the origin and function of Treg cells and their role in patients with B-cell tumours.
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Affiliation(s)
- Camilla A Lindqvist
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
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30
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Tio M, Cox MR, Eslick GD. Meta-analysis: coeliac disease and the risk of all-cause mortality, any malignancy and lymphoid malignancy. Aliment Pharmacol Ther 2012; 35:540-51. [PMID: 22239821 DOI: 10.1111/j.1365-2036.2011.04972.x] [Citation(s) in RCA: 97] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2011] [Revised: 11/15/2011] [Accepted: 12/12/2011] [Indexed: 02/06/2023]
Abstract
BACKGROUND Coeliac disease has been associated with an increased risk of mortality and malignancy. However, the strength of this association is conflicting among different studies. AIM To perform a systematic review and quantitative meta-analysis to determine the risk of all-cause mortality, any malignancy and lymphoid malignancy in coeliac disease patients. METHODS Four electronic databases (Medline, PubMed, Embase and Current Contents Connect) were searched to 4 January 2012, with no language restrictions. From 8698 citations identified, a total of 17 studies met our inclusion criteria. RESULTS The all-cause mortality meta-analysis showed an increased risk for all-cause mortality in coeliac patients [odds ratio (OR) 1.24; 95% confidence interval (CI) 1.19-1.30]. A subgroup analysis showed that patients identified by positive serology alone were also at an increased risk of all-cause mortality (OR 1.16; 95% CI 1.02-1.31). The non-Hodgkin lymphoma (NHL) meta-analysis showed an increased risk for NHL in coeliac patients (OR 2.61; 95% CI 2.04-3.33). A subgroup analysis showed that patients identified by positive serology alone were also at an increased risk of NHL (OR 2.55; 95% CI 1.02-6.36). The T-cell non-Hodgkin lymphoma (TNHL) meta-analysis showed an increased risk of TNHL (OR 15.84; 95% CI 7.85-31.94). The any malignancy meta-analysis showed no increased risk (OR 1.07; 95% CI 0.89-1.29). CONCLUSIONS Patients with coeliac disease are at an increased risk of mortality and non-Hodgkin lymphoma, particularly T-cell non-Hodgkin lymphoma; they do not have an increased risk of any malignancy overall. Serologically defined patients with coeliac disease have an elevated risk of mortality and non-Hodgkin lymphoma.
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Affiliation(s)
- M Tio
- The Whiteley-Martin Research Centre, The Discipline of Surgery, The University of Sydney, Sydney Medical School, Nepean, Penrith, NSW, Australia
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Abstract
Autoimmune rheumatic diseases (ARD), such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome (SS), have consistently been associated with the development of B-cell non-Hodgkin lymphoma (BCNHL). In this Review, we focus on reports published since 2006 and summarize the data regarding the BCNHL subtypes and clinical findings associated with this increased risk. Patients with these ARD, particularly those with detectable autoantibodies and systemic involvement, are at increased risk of developing BCNHL, especially diffuse large B-cell lymphoma and marginal zone lymphoma. SS shows the strongest association with BCNHL. Male sex, advanced age, prolonged disease course and increased disease severity, but not family history of autoimmune conditions, seem to be associated with an increased risk of non-Hodgkin lymphoma. Chronic immune stimulation, genetic and environmental factors and some immunosuppressive drugs might be involved in lymphomagenesis in these patients. The reason why some ARD are associated with BCNHL and other autoimmune diseases are not remains unclear. These associations are important as they provide information about the mechanisms of lymphomagenesis, and might help identify new therapeutic targets.
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Kane EV, Newton R, Roman E. Non-Hodgkin lymphoma and gluten-sensitive enteropathy: estimate of risk using meta-analyses. Cancer Causes Control 2011; 22:1435-44. [PMID: 21755296 DOI: 10.1007/s10552-011-9818-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2011] [Accepted: 07/05/2011] [Indexed: 12/21/2022]
Abstract
OBJECTIVES Gluten-sensitive enteropathy, including coeliac disease and dermatitis herpetiformis, is associated with non-Hodgkin lymphoma (NHL), and particularly enteropathy-associated T-cell lymphoma (EATCL). We conducted a meta-analysis to quantify the association. METHODS Fifty-four risk estimates (range 0.28-300) were pooled using random-effects meta-analysis. Potential sources of variation were examined using sensitivity analyses and meta-regression. RESULTS Thirty-one estimates with gluten-sensitive enteropathy diagnosed by serology then biopsy, serology alone, or recorded in medical notes accounted for half the variation in risks, giving a pooled estimate of 4.42 (95% confidence interval (CI) 3.72-5.26, I2 = 0%). Men and women had similar pooled risks. Risks were largest when these conditions were diagnosed using biopsy and lowest when self-reported. Study design, comparison population, geography or gluten-sensitive enteropathy type explained less of the variation. EATCL estimates ranged from 6 to 200; an association with diffuse large B-cell lymphoma (DLBCL) was also observed (pooled risk estimate = 1.97, 95% CI 1.23-3.15). CONCLUSIONS Where gluten-sensitive enteropathy was diagnosed using modern techniques, NHL risk was increased fourfold. At this level, one in 2,000 persons with gluten-sensitive enteropathy develops NHL each year. In addition to EATCL, DLBCL and possibly other subtypes may be linked to these conditions, and these weaker associations could be investigated in large population-based cohorts with biological samples.
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Affiliation(s)
- Eleanor V Kane
- Epidemiology and Genetics Unit, Department of Health Sciences, University of York, Seebohm Rowntree Building, Heslington, York, YO10 5DD, UK.
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