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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02733

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

 Abdulla Watad1,  Nicola L. Bragazzi2*,  Dennis McGonagle3, Mohammad Adawi4,  Yehuda J. Shoenfeld1, Doron Comaneshter5, Arnon Cohen5 and Howard Amital1
  • 1Tel Aviv University, Israel
  • 2University of Genoa, Italy
  • 3University of Leeds, United Kingdom
  • 4Bar-Ilan University, Israel
  • 5Clalit Health Services, Israel

Objectives: To test the hypothesis that familial Meditteranean fever (FMF) associated autoinflammation may exaggerate the tendency towards adaptive immunopathology or spondyloarthritis (SpA)-associated disorders including MHC class-I associated disorders but not classical MHC class II-associated disorders that exhibit transplacental autoimmunity including myasthenia gravis and pemphigus.
Methods: 7,747 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 and also evaluated 4 classical and strong MHC class-II associated disorders, namely pemphigus vulgaris, myasthenia gravis, sarcoidosis and pernicious anaemia, 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.
Results: FMF showed a strong association with MHC class I related diseases: OR 28.58 ([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 AS, and OR 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.

Keywords: Familial Mediterranean Fever, spondyloarhtritis, Crohn’s Disease, ulcerative colitis, MHC-I

Received: 06 Jun 2019; Accepted: 07 Nov 2019.

Copyright: © 2019 Watad, Bragazzi, McGonagle, Adawi, Shoenfeld, Comaneshter, Cohen 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.

* Correspondence: Mx. Nicola L. Bragazzi, University of Genoa, Genoa, Italy,