Watad, A, Bragazzi, NL, Adawi, M et al. (5 more authors) (2019) FMF Is Associated With a Wide Spectrum of MHC Class I- and Allied SpA Disorders but Not With Classical MHC Class II-Associated Autoimmune Disease: Insights From a Large Cohort Study. Frontiers in Immunology, 10. 2733. ISSN 1664-3224
Abstract
Objectives: To test the hypothesis that familial Mediterranean fever (FMF)-associated autoinflammation may exaggerate the tendency toward adaptive immunopathology or spondyloarthritis (SpA)-associated disorders including major histocompatibility complex (MHC) class I associated disorders but not classical MHC class II-associated disorders that exhibit transplacental autoimmunity including myasthenia gravis and pemphigus.
Methods: Seven thousand seven hundred forty-seven FMF patients and 10,080 age- and sex-matched controls in the Clalit Health Services medical database were identified and compared in terms of prevalence of SpA-associated disorders. We also evaluated four classical and strong MHC class II-associated disorders, namely, pemphigus vulgaris, myasthenia gravis, sarcoidosis, and pernicious anemia, to ascertain whether such associations with SpA-spectrum disease were specific or merely reflected the non-specific consequences of innate immune system activation on driving divergent types of immunity. The diagnosis of FMF was based on the medical records and not genetically proven.
Results: FMF showed a strong association with MHC class I-related diseases: odds ratio (OR) of 28.58 [95% confidence interval (95% CI), 6.93–117.87; p < 0.0001] for Behçet's disease, OR of 10.33 (95% CI, 4.09–26.09; p < 0.0001) for ankylosing spondylitis, and OR of 1.67 (95% CI, 1.19–2.33; p = 0.0029) for psoriasis. For weakly MHC class I-linked diseases, an OR of 3.76 (95% CI, 2.48–5.69; p < 0.0001) for Crohn's disease and OR of 2.64 (95% CI, 1.52–4.56; p = 0.0005) for ulcerative colitis were found. No association was found between FMF and the four MHC class II-associated autoimmune disorders.
Conclusion: FMF patients are associated with increased risk of SpA-related disease diagnosis including MHC-I-opathies but not MHC-II-associated autoimmune diseases, suggesting that tissue-specific dysregulation of innate immunity share between FMF and SpA spectrum disorders may drive adaptive immune MHC class I-associated conditions.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 Watad, Bragazzi, Adawi, Shoenfeld, Comaneshter, Cohen, McGonagle and Amital. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Experimental Musculoskeletal Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 23 Dec 2019 09:53 |
Last Modified: | 25 Jun 2023 22:05 |
Status: | Published |
Publisher: | Frontiers Media |
Identification Number: | 10.3389/fimmu.2019.02733 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:154877 |