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Han M, Luo J, Zhou W, Wen S, Zhou Y, Ye Y, Ge X. From skin testing to molecular diagnostics: the precision leap in dust mite allergy diagnosis and clinical translation challenges. FRONTIERS IN ALLERGY 2025; 6:1598575. [PMID: 40538626 PMCID: PMC12176741 DOI: 10.3389/falgy.2025.1598575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2025] [Accepted: 05/13/2025] [Indexed: 06/22/2025] Open
Abstract
Dust mites are ubiquitous in human living environments and represent the primary source of indoor air allergens worldwide. They are capable of triggering allergic rhinitis, conjunctivitis, asthma, atopic dermatitis, and other allergic conditions. Long-term avoidance of dust mite allergens should decrease sensitization, significantly improves skin lesions, and reduces both the development and severity of respiratory diseases. Therefore, early diagnosis of dust mite allergy is critical for effective treatment and intervention. This review summarizes the existing methods for detecting dust mite allergy, which include both in vivo and in vitro approaches-such as skin prick testing(SPT), atopy patch testing(APT), provocation tests, basophil activation test (BAT), and molecular component-resolved diagnostics(CRD)-and analyzes the underlying principles, advantages, and limitations of each method to serve as a reference for the development of future detection methods.
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Affiliation(s)
- Ming Han
- Department of Pediatrics, The Affiliated Wuxi Second People’s Hospital of Jiangnan University, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu, China
| | - Jindan Luo
- Department of Pediatrics, Wuxi Second People’s Hospital, Nanjing Medical University, Wuxi, Jiangsu, China
| | - Wenjing Zhou
- Department of Pediatrics, The Affiliated Wuxi Second People’s Hospital of Jiangnan University, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu, China
| | - Shuhui Wen
- Department of Pediatrics, The Affiliated Wuxi Second People’s Hospital of Jiangnan University, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu, China
| | - Yi Zhou
- Department of Pediatrics, The Affiliated Wuxi Second People’s Hospital of Jiangnan University, Wuxi, Jiangsu, China
| | - Yanjuan Ye
- Department of Pediatrics, The Affiliated Wuxi Second People’s Hospital of Jiangnan University, Wuxi, Jiangsu, China
| | - Xiaoli Ge
- Department of Pediatrics, The Affiliated Wuxi Second People’s Hospital of Jiangnan University, Wuxi, Jiangsu, China
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Blank S, Korošec P, Slusarenko BO, Ollert M, Hamilton RG. Venom Component Allergen IgE Measurement in the Diagnosis and Management of Insect Sting Allergy. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2025; 13:1-14. [PMID: 39097146 DOI: 10.1016/j.jaip.2024.07.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Revised: 07/03/2024] [Accepted: 07/15/2024] [Indexed: 08/05/2024]
Abstract
Accurate identification of allergy-eliciting stinging insect(s) is essential to ensuring effective management of Hymenoptera venom-allergic individuals with venom-specific immunotherapy. Diagnostic testing using whole-venom extracts with skin tests and serologic-based analyses remains the first level of discrimination for honeybee versus vespid venom sensitization in patients with a positive clinical history. As a second-level evaluation, serologic testing using molecular venom allergens can further discriminate genuine sensitization (honeybee venom: Api m 1, 3, 4, and 10 vs yellow jacket venom/Polistes dominula venom Ves v 1/Pol d 1 and Ves v 5/Pol d 5) from interspecies cross-reactivity (hyaluronidases [Api m 2, Ves v 2, and Pol d 2] and dipeptidyl peptidases IV [Api m 5, Ves v 3, and Pol d 3]). Clinical laboratories use a number of singleplex, oligoplex, and multiplex immunoassays that employ both extracted whole-venom and molecular venom allergens (highlighted earlier) for confirmation of allergic venom sensitization. Established quantitative singleplex autoanalyzers have general governmental regulatory clearance worldwide for venom-allergic patient testing with maximally achievable analytical sensitivity (0.1 kUA/L) and confirmed reproducibility (interassay coefficient of variation <10%). Emerging oligoplex and multiplex (fixed-panel) assays conserve on serum and are more cost-effective, but they need regulatory clearance in some countries and are prone to higher rates of detecting asymptomatic sensitization. Ultimately, the patient's clinical history, combined with proof of sensitization, is the final arbiter in the diagnosis of Hymenoptera venom allergy.
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Affiliation(s)
- Simon Blank
- Center of Allergy and Environment, Technical University of Munich, School of Medicine and Health and Helmholtz Munich, German Research Center for Environmental Health, Munich, Germany.
| | - Peter Korošec
- Laboratory for Clinical Immunology and Molecular Genetics, University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia; Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia; Faculty of Medicine, University of Maribor, Maribor, Slovenia
| | - Benjamin O Slusarenko
- Center of Allergy and Environment, Technical University of Munich, School of Medicine and Health and Helmholtz Munich, German Research Center for Environmental Health, Munich, Germany
| | - Markus Ollert
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Department of Dermatology and Allergy Centre, Odense Research Center for Anaphylaxis, Odense University Hospital, Odense, Denmark
| | - Robert G Hamilton
- Johns Hopkins University School of Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, Md.
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Sokolov P, Evsegneeva I, Karaulov A, Sukhanova A, Nabiev I. Allergen Microarrays and New Physical Approaches to More Sensitive and Specific Detection of Allergen-Specific Antibodies. BIOSENSORS 2024; 14:353. [PMID: 39056629 PMCID: PMC11275078 DOI: 10.3390/bios14070353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 07/16/2024] [Accepted: 07/18/2024] [Indexed: 07/28/2024]
Abstract
The prevalence of allergic diseases has increased tremendously in recent decades, which can be attributed to growing exposure to environmental triggers, changes in dietary habits, comorbidity, and the increased use of medications. In this context, the multiplexed diagnosis of sensitization to various allergens and the monitoring of the effectiveness of treatments for allergic diseases become particularly urgent issues. The detection of allergen-specific antibodies, in particular, sIgE and sIgG, is a modern alternative to skin tests due to the safety and efficiency of this method. The use of allergen microarrays to detect tens to hundreds of allergen-specific antibodies in less than 0.1 mL of blood serum enables the transition to a deeply personalized approach in the diagnosis of these diseases while reducing the invasiveness and increasing the informativeness of analysis. This review discusses the technological approaches underlying the development of allergen microarrays and other protein microarrays, including the methods of selection of the microarray substrates and matrices for protein molecule immobilization, the obtainment of allergens, and the use of different types of optical labels for increasing the sensitivity and specificity of the detection of allergen-specific antibodies.
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Affiliation(s)
- Pavel Sokolov
- Life Improvement by Future Technologies (LIFT) Center, 143025 Moscow, Russia
- Laboratory of Nano-Bioengineering, National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), 115409 Moscow, Russia
| | - Irina Evsegneeva
- Department of Clinical Immunology and Allergology, Institute of Molecular Medicine, Sechenov First Moscow State Medical University (Sechenov University), 119146 Moscow, Russia; (I.E.); (A.K.)
| | - Alexander Karaulov
- Department of Clinical Immunology and Allergology, Institute of Molecular Medicine, Sechenov First Moscow State Medical University (Sechenov University), 119146 Moscow, Russia; (I.E.); (A.K.)
| | - Alyona Sukhanova
- Laboratoire BioSpecT, Université de Reims Champagne-Ardenne, 51100 Reims, France;
| | - Igor Nabiev
- Life Improvement by Future Technologies (LIFT) Center, 143025 Moscow, Russia
- Laboratory of Nano-Bioengineering, National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), 115409 Moscow, Russia
- Department of Clinical Immunology and Allergology, Institute of Molecular Medicine, Sechenov First Moscow State Medical University (Sechenov University), 119146 Moscow, Russia; (I.E.); (A.K.)
- Laboratoire BioSpecT, Université de Reims Champagne-Ardenne, 51100 Reims, France;
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Packi K, Rudek A, Matysiak J, Klimczak S, Matuszewska E, Rzetecka N, Matysiak J. Food Allergies and Parasites in Children. Foods 2023; 12:2465. [PMID: 37444203 DOI: 10.3390/foods12132465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 06/19/2023] [Accepted: 06/21/2023] [Indexed: 07/15/2023] Open
Abstract
The dynamically growing incidence of food allergies forces the scientific community to develop new methods for their diagnosis, differentiation, and effective treatment. Parasitoses appear much less frequently in the scientific literature, as well as among the presumed causes of numerous conditions. The similarity of inflammatory mechanisms in allergies and parasitosis necessitates a revision of current diagnostic standards. A lack of specificity and the coincidence of symptoms at an early stage of disease can lead to misdiagnosis. In this paper, we attempted to perform a comparative analysis of the similarities and differences in symptoms for these two types of diseases. We described the molecular mechanisms and metabolic pathways of food allergy and parasitosis. We presented the available research methods and directions of ongoing studies aimed at implementing precise medical techniques for differential diagnosis. We discussed the allergenic properties of certain parasite proteins, using the example of myofibrillar tropomyosins from the nematode Anisakis simplex. The literature in the fields of allergology and parasitology leads to the conclusion that it is reasonable to run parallel allergological and parasitological diagnostics in patients with non-specific symptoms. This approach will facilitate accurate and early diagnosis and implementation of effective therapy.
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Affiliation(s)
- Kacper Packi
- Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, 60-806 Poznan, Poland
- AllerGen Center of Personalized Medicine, 97-300 Piotrkow Trybunalski, Poland
| | - Alicja Rudek
- AllerGen Center of Personalized Medicine, 97-300 Piotrkow Trybunalski, Poland
| | - Joanna Matysiak
- Faculty of Health Sciences, Calisia University-Kalisz, 62-800 Kalisz, Poland
| | - Sylwia Klimczak
- AllerGen Center of Personalized Medicine, 97-300 Piotrkow Trybunalski, Poland
- Department of Nucleic Acid Biochemistry, Medical University of Lodz, 92-213 Lodz, Poland
| | - Eliza Matuszewska
- Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, 60-806 Poznan, Poland
| | - Natalia Rzetecka
- Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, 60-806 Poznan, Poland
| | - Jan Matysiak
- Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, 60-806 Poznan, Poland
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Walsemann T, Böttger M, Traidl S, Schwager C, Gülsen A, Freimooser S, Roesner LM, Werfel T, Jappe U. Specific IgE against the house dust mite allergens Der p 5, 20 and 21 influences the phenotype and severity of atopic diseases. Allergy 2023; 78:731-742. [PMID: 36239002 DOI: 10.1111/all.15553] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 09/12/2022] [Accepted: 09/23/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND House dust mites (HDM) are among the most important sources for airborne allergens with high relevance for atopic diseases. Routine tests contain only 4 of 32 registered allergens of Dermatophagoides pteronyssinus. Clinical relevance and pathomechanistic properties of many allergens are not well understood. OBJECTIVE The association of several HDM allergens with allergic rhinitis, allergic asthma, and atopic dermatitis was investigated to identify allergens with biomarker potential and to transfer them into diagnostics. METHODS Eight out of nine D. pteronyssinus allergens (nDer p 1, rDer p 2, rDer p 5, rDer p 7, rDer p 10, rDer p 13, rDer p 20, rDer p 21, rDer p 23) were recombinantly expressed and purified. Sensitization patterns of 384 HDM-allergic individuals exhibiting different clinical phenotypes were analyzed with a serum-saving multiplex array. RESULTS Sensitization to more than three mite allergens (sensitization count) was associated with allergic asthma and/or atopic dermatitis. Reactions to Der p 5 and Der p 21 were more frequent in allergic asthma compared to allergic rhinitis. Atopic dermatitis patients were more often sensitized to Der p 5, Der p 20, and Der p 21 among others. Der p 20-IgE > 80 kU/L was associated with severe atopic dermatitis in 75% of patients. CONCLUSION This study demonstrates the clinical importance of the sensitization count and of certain allergens (Der p 5, Der p 20, and Der p 21) not available for routine diagnostics yet. Implementing them as well as the sensitization count in diagnostic measures will improve diagnosis and risk assessment of HDM-allergic patients.
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Affiliation(s)
- Theresa Walsemann
- Division of Clinical and Molecular Allergology, Priority Area Asthma and Allergy, Research Center Borstel, German Center for Lung Research (DZL) Airway Research Center North (ARCN), Borstel, Germany
| | - Marisa Böttger
- Division of Clinical and Molecular Allergology, Priority Area Asthma and Allergy, Research Center Borstel, German Center for Lung Research (DZL) Airway Research Center North (ARCN), Borstel, Germany
| | - Stephan Traidl
- Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany
| | - Christian Schwager
- Division of Clinical and Molecular Allergology, Priority Area Asthma and Allergy, Research Center Borstel, German Center for Lung Research (DZL) Airway Research Center North (ARCN), Borstel, Germany
| | - Askin Gülsen
- Interdisciplinary Allergy Outpatient Clinic, Department of Pneumology, University of Luebeck, Luebeck, Germany
| | - Sina Freimooser
- Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany
| | - Lennart Matthias Roesner
- Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.,Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
| | - Thomas Werfel
- Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.,Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
| | - Uta Jappe
- Division of Clinical and Molecular Allergology, Priority Area Asthma and Allergy, Research Center Borstel, German Center for Lung Research (DZL) Airway Research Center North (ARCN), Borstel, Germany.,Interdisciplinary Allergy Outpatient Clinic, Department of Pneumology, University of Luebeck, Luebeck, Germany
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Atopic Status in Children with Asthma and Respiratory Allergies—Comparative Analysis of Total IgE, ImmunoCAP Phadiatop/fx5 and Euroimmun Pediatric Immunoblot. SINUSITIS 2021. [DOI: 10.3390/sinusitis6010001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Introduction: An atopic status assessment (skin prick test or specific immunoglobulin (sIgE)) in asthmatic children is considered a milestone in identifying potential risk factors and triggers provoking loss of asthma control and asthma exacerbation. Objective: The study aims to perform a comparative analysis of different laboratory methods for a serological assessment of an atopic status in asthma and respiratory allergies in children. Material and methods: A total of 86 children were included, all of whom were diagnosed with bronchial asthma, aged from 5 to 17 years and screened for total IgE level using enzyme-linked immunosorbent assay (ELISA). In 48 randomly selected children, we performed a semi-quantitative serological in vitro assessment of the specific IgE antibodies against food and aeroallergen, using two different laboratory methods—Euroimmun Immunoblot and ImmunoCAP (Phadiatop/fx5). Results: In 70% of the children with a history of allergies, and 65.3% without clinically manifested allergies, multiscreen test ImmunoCAP Phadiatop/fx5 showed positivity and confirmed atopy. Our results showed a significant moderate to strong correlation between multiscreen ImmunoCAP Phadiatop/fx5, and Euroimmun specific IgE titers against aero-allergens—cats, mites, tree mix and food allergens—soy, wheat (р = 0.006), rice, р = 0.090), apple р = 0.007) and peanut. A sensitivity of 63% and specificity of 73.5% was observed for EUROIMMUN Pediatric (food allergens, IgE titer > 1) compared with the gold standard ImmunoCap/fx5. The mean value of total IgE is significantly higher in children with asthma and concomitant with allergic rhinitis compared to those without allergic rhinitis (mean 202.52 U/mL, IQR 102.50 (24.20–363.95) vs. 316.68, IQR 261.00 (109.20–552.50), p = 0.005). Conclusion: Establishing the spectrum of the most common respiratory and food allergens is an essential factor for maintaining asthma control, both through a strategy to avoid allergen exposure and by developing a recommendation plan. The immunoblotting technique is easily applicable in daily clinical and laboratory practice. It is also a cost-effective and reliable alternative to the “gold standard” ImmunoCAP Phadiatop/fx5 in diagnosing atopy in children.
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Doyen V, Truyens C, Nhu Thi H, Mong HTT, Le Chi T, De Blay F, Huynh PTN, Michel O, Corazza F. Helminth infection induces non-functional sensitization to house dust mites. PLoS One 2021; 16:e0253887. [PMID: 34197505 PMCID: PMC8248592 DOI: 10.1371/journal.pone.0253887] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 06/14/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND IgE characterizes the humoral response of allergic sensitization but less is known about what modulates its function and why some patients present clinical symptoms for a given IgE level and others do not. An IgE response also occurs during helminth diseases, independently of allergic symptoms. This response could be a model of non-functional IgE. OBJECTIVE To study the IgE response against environmental allergens induced during natural helminth infection. METHODS In 28 non allergic subjects from the periphery of Ho Chi Minh city with (H+, n = 18) and without helminth infection (H-, n = 10), we measured IgE and IgG4 against several components of Dermatophagoïdes pteronyssinus (Dpt) and Ascaris (a marker of immunization against nematodes), and determined the IgE component sensitization profile using microarray ISAC biochips. The functional ability of IgE to induce degranulation of cultured mast cells was evaluated in the presence of Dpt. RESULTS Non allergic H+ subjects exhibited higher levels of IgE against Dpt compared to H- subjects. Dpt IgE were not functional in vitro and did not recognize usual Dpt major allergens. IgE recognized other component allergens that belong to different protein families, and most were glycosylated. Depletion of IgE recognizing carbohydrate cross-reactive determinant (CCD) did not induce a reduction in Dpt IgE. The Dpt IgG4 were not significantly different. CONCLUSION Helminth infections induced IgE against allergens such as Dpt and molecular components that belong to different sources as well as against CCD (such as β-1,2-xylose and/or ⍺-1,3-fucose substituted N-glycans). Dpt IgE were not able to induce degranulation of mast cells and were not explained by sensitization to usual major allergens or N-glycans.
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Affiliation(s)
- Virginie Doyen
- Clinic of Immunoallergology, CHU Brugmann, Brussels, Belgium
- Laboratory of Translational Research, ULB223, CHU Brugmann, Université Libre de Bruxelles (ULB), Brussels, Belgium
- * E-mail:
| | - Carine Truyens
- Parasitology Laboratory, ULB Center for Research in immunology (U-CRI), Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Hoa Nhu Thi
- Parasitology and Mycology Department, Pham Ngoc Thach University of Medicine, Ho Chi Minh, Vietnam
| | - Hiep Tran Thi Mong
- Department of Family Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh, Vietnam
| | - Thanh Le Chi
- Immunology Laboratory, Pasteur Institute, Ho Chi Minh, Vietnam
| | - Frederic De Blay
- Chest Diseases Department, Strasbourg University Hospital, Strasbourg, France
- Biocluster des Haras, ALYATEC, Strasbourg, France
| | | | - Olivier Michel
- Clinic of Immunoallergology, CHU Brugmann, Brussels, Belgium
| | - Francis Corazza
- Laboratory of Translational Research, ULB223, CHU Brugmann, Université Libre de Bruxelles (ULB), Brussels, Belgium
- Laboratory of Translational Research, ULB223, CHU Brugmann, Immunology Laboratory, LHUB-ULB, Université Libre de Bruxelles (ULB), Brussels, Belgium
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8
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Hoang JA, Celik A, Lupinek C, Valenta R, Duan L, Dai R, Brydges MG, Dubeau A, Lépine C, Wong S, Alexanian‐Farr M, Magder A, Subbarao P, Upton JEM, Schmidthaler K, Szépfalusi Z, Ramani A, Eiwegger T. Modeling the conversion between specific IgE test platforms for nut allergens in children and adolescents. Allergy 2021; 76:831-841. [PMID: 32738829 DOI: 10.1111/all.14529] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 07/03/2020] [Accepted: 07/14/2020] [Indexed: 01/01/2023]
Abstract
BACKGROUND Multiplex tests allow for measurement of allergen-specific IgE responses to multiple extracts and molecular allergens and have several advantages for large cohort studies. Due to significant methodological differences, test systems are difficult to integrate in meta-analyses/systematic reviews since there is a lack of datasets with direct comparison. We aimed to create models for statistical integration of allergen-specific IgE to peanut/tree nut allergens from three IgE test platforms. METHODS Plasma from Canadian and Austrian children/adolescents with peanut/tree nut sensitization and a cohort of sensitized, high-risk, pre-school asthmatics (total n = 166) were measured with three R&D multiplex IgE test platforms: Allergy Explorer version 1 (ALEX) (Macro Array Dx), MeDALL-chip (Mechanisms of Development of Allergy) (Thermo Fisher), and EUROLINE (EUROIMMUN). Skin prick test (n = 51) and ImmunoCAP (Thermo Fisher) (n = 62) results for extracts were available in a subset. Regression models (Multivariate Adaptive Regression Splines, local polynomial regression) were applied if >30% of samples were positive to the allergen. Intra-test correlations between PR-10 and nsLTP allergens were assessed. RESULTS Using two regression methods, we demonstrated the ability to model allergen-specific relationships with acceptable measures of fit (r2 = 94%-56%) for peanut and tree nut sIgE testing at the extract and molecular-level, in order from highest to lowest: Ara h 2, Ara h 6, Jug r 1, Ana o 3, Ara h 1, Jug r 2, and Cor a 9. CONCLUSION Our models support the notion that quantitative conversion is possible between sIgE multiplex platforms for extracts and molecular allergens and may provide options to aggregate data for future meta-analysis.
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Affiliation(s)
- Jennifer A. Hoang
- Translational Medicine Program Research Institute, Hospital for Sick Children Toronto ON Canada
| | - Alper Celik
- Centre for Computational Medicine Hospital for Sick Children Toronto ON Canada
| | - Christian Lupinek
- Division of Immunopathology Department of Pathophysiology and Allergy Research Center for Pathophysiology, Infectiology and Immunology Medical University of Vienna Vienna Austria
| | - Rudolf Valenta
- Division of Immunopathology Department of Pathophysiology and Allergy Research Center for Pathophysiology, Infectiology and Immunology Medical University of Vienna Vienna Austria
- NRC Institute of Immunology FMBA of Russia Moscow Russia
- Laboratory for Immunopathology Department of Clinical Immunology and Allergy Sechenov First Moscow State Medical University Moscow Russia
- Karl Landsteiner University of Health Sciences Krems Austria
| | - Lucy Duan
- Division of Immunology and Allergy Food Allergy and Anaphylaxis Program Department of Pediatrics The Hospital for Sick Children Toronto ON Canada
| | - Ruixue Dai
- Translational Medicine Program Research Institute, Hospital for Sick Children Toronto ON Canada
| | - May G. Brydges
- Translational Medicine Program Research Institute, Hospital for Sick Children Toronto ON Canada
| | - Aimée Dubeau
- Translational Medicine Program Research Institute, Hospital for Sick Children Toronto ON Canada
| | - Claire Lépine
- Translational Medicine Program Research Institute, Hospital for Sick Children Toronto ON Canada
| | - Samantha Wong
- Division of Immunology and Allergy Food Allergy and Anaphylaxis Program Department of Pediatrics The Hospital for Sick Children Toronto ON Canada
| | - Mara Alexanian‐Farr
- Division of Immunology and Allergy Food Allergy and Anaphylaxis Program Department of Pediatrics The Hospital for Sick Children Toronto ON Canada
| | - Ahuva Magder
- Division of Immunology and Allergy Food Allergy and Anaphylaxis Program Department of Pediatrics The Hospital for Sick Children Toronto ON Canada
| | - Padmaja Subbarao
- Translational Medicine Program Research Institute, Hospital for Sick Children Toronto ON Canada
- Division of Respiratory Medicine and Translational Medicine Departments of Pediatrics and Physiology Hospital for Sick Children and University of Toronto Toronto ON Canada
| | - Julia E. M. Upton
- Division of Immunology and Allergy Food Allergy and Anaphylaxis Program Department of Pediatrics The Hospital for Sick Children Toronto ON Canada
| | - Klara Schmidthaler
- Division of Pediatric Pulmonology, Allergology and Endocrinology Department of Pediatric and Adolescent Medicine Medical University of Vienna Vienna Austria
| | - Zsolt Szépfalusi
- Division of Pediatric Pulmonology, Allergology and Endocrinology Department of Pediatric and Adolescent Medicine Medical University of Vienna Vienna Austria
| | - Arun Ramani
- Centre for Computational Medicine Hospital for Sick Children Toronto ON Canada
| | - Thomas Eiwegger
- Translational Medicine Program Research Institute, Hospital for Sick Children Toronto ON Canada
- Division of Immunology and Allergy Food Allergy and Anaphylaxis Program Department of Pediatrics The Hospital for Sick Children Toronto ON Canada
- Departments of Pediatrics and Immunology University of Toronto Toronto ON Canada
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9
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Keshavarz B, Platts-Mills TAE, Wilson JM. The use of microarray and other multiplex technologies in the diagnosis of allergy. Ann Allergy Asthma Immunol 2021; 127:10-18. [PMID: 33450398 DOI: 10.1016/j.anai.2021.01.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 12/18/2020] [Accepted: 01/04/2021] [Indexed: 12/30/2022]
Abstract
OBJECTIVE To give an overview and describe the strengths and weaknesses of immunoglobulin E (IgE) microarray and other multiplex assays that have been developed and are being used for allergy diagnostics. DATA SOURCES Queries for IgE microarray and multiplex assays were conducted with PubMed and Google Scholar, searching for primary articles and review papers. STUDY SELECTIONS We focused on articles written in English on commercially available IgE multiplex assays that were reported in the allergy and immunology literature. RESULTS Several commercial IgE assays that use microarray or other multiplex technology have been developed, and some have been implemented into clinical practice in Europe and Asia, with the Immuno Solid-Phase Allergen Chip being the most widely studied. Results of these assays generally correlate with results using "singleplex" IgE assays (eg, ImmunoCAP), though there can be variability among products and among allergens. A strength of the microarray technology is that IgE to a large number of allergens can be detected simultaneously in a single test, and only a small amount of patient serum is required. Cost, inadequate sensitivity under some scenarios, and difficulties with data interpretation, in some cases of 100 or more allergens, can be limitations. CONCLUSION IgE microarray assays are already a valuable tool in research applications. These assays, and also other forms of IgE multiplex assays, are likely to play an important role in the clinical practice of allergy in the future. Additional studies focused on clinical outcomes, and the development of more targeted allergen panels could facilitate increased clinical use.
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Affiliation(s)
- Behnam Keshavarz
- Division of Allergy and Immunology, Department of Medicine, University of Virginia, Charlottesville, Virginia
| | - Thomas A E Platts-Mills
- Division of Allergy and Immunology, Department of Medicine, University of Virginia, Charlottesville, Virginia
| | - Jeffrey M Wilson
- Division of Allergy and Immunology, Department of Medicine, University of Virginia, Charlottesville, Virginia.
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10
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Hamilton RG, Hemmer W, Nopp A, Kleine-Tebbe J. Advances in IgE Testing for Diagnosis of Allergic Disease. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2020; 8:2495-2504. [PMID: 32717438 DOI: 10.1016/j.jaip.2020.07.021] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 07/21/2020] [Accepted: 07/22/2020] [Indexed: 01/10/2023]
Abstract
Since its discovery in 1967, IgE antibody detection in skin and blood has identified a state of allergic sensitization and served as a necessary but not sufficient risk factor that requires objective symptoms to make the definitive diagnosis of human allergic disease. More recently, quantitative IgE antibody levels in serum against allergenic extracts, molecules, and epitopes have pushed its application into more accurately identifying the specificity of the allergic response for targeting immunotherapy, predicting allergic symptom severity after allergen exposure, and attempting to distinguish tolerance from food allergy. This review examines new in vivo and in vitro developments in the design, performance, interference, and application of the methods used to identify allergic sensitization. The increasing accepted applications of molecular allergen and allergen epitope-based IgE antibody measurements, especially as applied to food allergy diagnosis and management, are highlighted as state-of-the-art advances. Despite these major advances in allergic sensitization documentation, their ultimate value requires integration by the clinician with the patient's history and pretest probability of disease.
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Affiliation(s)
- Robert G Hamilton
- Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md.
| | | | - Anna Nopp
- Department of Clinical Science and Education, Karolinska Institutet, Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden
| | - Jörg Kleine-Tebbe
- Allergy & Asthma Center Westend, Outpatient Clinic Hanf, Ackermann & Kleine-Tebbe, Berlin, Germany
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Roethlisberger S, Karoui O, Mapelli D, Audran R, Aubert V, Girard L, Rebeaud F, Leimgruber A, Buss G, Duc J, Langner-Viviani F, Maerki I, Spertini F. Novel Nanofluidic IgE Assay versus a Reference Method: A Real-World Comparison. Int Arch Allergy Immunol 2019; 180:28-36. [DOI: 10.1159/000500830] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Accepted: 05/07/2019] [Indexed: 11/19/2022] Open
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12
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Popescu FD, Vieru M. Precision medicine allergy immunoassay methods for assessing immunoglobulin E sensitization to aeroallergen molecules. World J Methodol 2018; 8:17-36. [PMID: 30519536 PMCID: PMC6275558 DOI: 10.5662/wjm.v8.i3.17] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2018] [Revised: 08/17/2018] [Accepted: 10/09/2018] [Indexed: 02/06/2023] Open
Abstract
Molecular-based allergy diagnosis for the in vitro assessment of a patient immunoglobulin E (IgE) sensitization profile at the molecular level uses allergen molecules (also referred to as allergen components), which may be well-defined, highly purified, natural allergen components or recombinant allergens. Modern immunoassay methods used for the detection of specific IgE against aeroallergen components are either singleplex (such as the fluorescence enzyme immunoassay with capsulated cellulose polymer solid-phase coupled allergens, the enzyme-enhanced chemiluminescence immunoassay and the reversed enzyme allergosorbent test, with liquid-phase allergens), multiparameter (such as the line blot immunoassay for defined partial allergen diagnostics with allergen components coating membrane strips) or multiplex (such as the microarray-based immunoassay on immuno solid-phase allergen chip, and the two new multiplex nanotechnology-based immunoassays: the patient-friendly allergen nano-bead array, and the macroarray nanotechnology-based immunoassay used as a molecular allergy explorer). The precision medicine diagnostic work-up may be organized as an integrated “U-shape” approach, with a “top-down” approach (from symptoms to molecules) and a “bottom-up” approach (from molecules to clinical implications), as needed in selected patients. The comprehensive and accurate IgE sensitization molecular profiling, with identification of the relevant allergens, is indicated within the framework of a detailed patient’s clinical history to distinguish genuine IgE sensitization from sensitization due to cross-reactivity (especially in polysensitized patients), to assess unclear symptoms and unsatisfactory response to treatment, to reveal unexpected sensitizations, and to improve assessment of severity and risk aspects in some patients. Practical approaches, such as anamnesis molecular thinking, laboratory molecular thinking and postmolecular anamnesis, are sometimes applied. The component-resolved diagnosis of the specific IgE repertoire has a key impact on optimal decisions making for prophylactic and specific immunotherapeutic strategies tailored for the individual patient.
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Affiliation(s)
- Florin-Dan Popescu
- Department of Allergology, “Carol Davila” University of Medicine and Pharmacy, Bucharest 022441, Romania
- Department of Allergology and Clinical Immunology, “Nicolae Malaxa” Clinical Hospital, Bucharest 022441, Romania
| | - Mariana Vieru
- Department of Allergology, “Carol Davila” University of Medicine and Pharmacy, Bucharest 022441, Romania
- Department of Allergology and Clinical Immunology, “Nicolae Malaxa” Clinical Hospital, Bucharest 022441, Romania
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Amoah AS, Boakye DA, Yazdanbakhsh M, van Ree R. Influence of Parasitic Worm Infections on Allergy Diagnosis in Sub-Saharan Africa. Curr Allergy Asthma Rep 2017; 17:65. [PMID: 28861721 PMCID: PMC5579067 DOI: 10.1007/s11882-017-0733-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Epidemiological studies from Sub-Saharan Africa indicate that allergies are on the rise in this region especially in urban compared to rural areas. This increase has been linked to improved hygiene, lifestyle changes, and lower exposure to pathogens in childhood. Reduced exposure to parasitic worm (helminth) infections and allergy outcomes has been the focus of a number of population studies over the years. Paradoxically, there are parallels in the immune responses to helminths and to allergies. Both conditions are associated with elevated levels of immunoglobulin E, high numbers of T helper 2 cells, eosinophils, and mast cells. These immune parallels have meant that the diagnosis of allergies in parts of the world where helminths are endemic can be hampered. The aim of this review is to examine observations from population studies conducted in Sub-Saharan Africa that demonstrate how helminth infections influence the parameters used to diagnose allergy outcomes in this region. We explore specifically how helminth infections hinder the in vitro diagnosis of allergic sensitization, influence the clinical manifestations of allergy, and also the effect of anthelmintic treatment on allergy outcomes. Advancing our understanding of how helminths influence allergy diagnosis is imperative for the development of improved tools to assess, diagnose, and treat allergic disorders in both helminth-endemic and non-endemic countries worldwide.
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Affiliation(s)
- Abena S Amoah
- Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
| | - Daniel A Boakye
- Department of Parasitology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana
| | - Maria Yazdanbakhsh
- Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
| | - Ronald van Ree
- Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands
- Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, The Netherlands
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Alessandri C, Ferrara R, Bernardi ML, Zennaro D, Tuppo L, Giangrieco I, Tamburrini M, Mari A, Ciardiello MA. Diagnosing allergic sensitizations in the third millennium: why clinicians should know allergen molecule structures. Clin Transl Allergy 2017; 7:21. [PMID: 28725346 PMCID: PMC5513363 DOI: 10.1186/s13601-017-0158-7] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Accepted: 06/05/2017] [Indexed: 01/06/2023] Open
Abstract
Diagnostic tests to detect allergic sensitization were introduced at the end of the nineteenth century but only in the late 1990s did the advent of molecular allergology revolutionize the approach to the allergic patient. Personalized Medicine, a medical procedure that separates patients into different groups with different medical decisions, practices and interventions has sanctioned this change. In fact, in the last few years molecular allergology and the observation that not every patient has the same allergic profile, even when allergic to the same allergenic source, has originated the concept "one size does not fit all". This new approach requires the identification of still unknown allergens, but also the more detailed investigation of those already known. In depth studies of the structure-function relationships in allergenic molecules can reveal the structural determinants involved in the IgE-binding. Then, the knowledge of the epitope profile of each allergen and of the environmental/experimental conditions affecting the exposure of IgE-binding epitopes can provide important contributions to the understanding of cross-reaction processes and to the improvement of diagnosis, immunotherapy and the overall patient treatment. The evolution of diagnostic systems cannot ignore these new needs in this field.
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Affiliation(s)
- C Alessandri
- CAAM - Centri Associati di Allergologia Molecolare, Rome, Italy
| | - R Ferrara
- CAAM - Centri Associati di Allergologia Molecolare, Rome, Italy
| | - M L Bernardi
- CAAM - Centri Associati di Allergologia Molecolare, Rome, Italy
| | - D Zennaro
- CAAM - Centri Associati di Allergologia Molecolare, Rome, Italy
| | - L Tuppo
- Istituto di Bioscienze e Biorisorse - IBBR-CNR, Naples, Italy
| | - I Giangrieco
- Istituto di Bioscienze e Biorisorse - IBBR-CNR, Naples, Italy
| | - M Tamburrini
- Istituto di Bioscienze e Biorisorse - IBBR-CNR, Naples, Italy
| | - A Mari
- CAAM - Centri Associati di Allergologia Molecolare, Rome, Italy.,Allergy Data Laboratories s.c., Latina, Italy
| | - M A Ciardiello
- Istituto di Bioscienze e Biorisorse - IBBR-CNR, Naples, Italy
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