FRI0620 FMF PATIENTS HAVE A HIGHER PREVALENCE OF SPA-RELATED DISORDERS INCLUDING MHC-I-OPATHIES THAN CONTROLS: INSIGHTS FROM A LARGE COHORT STUDY
Authors: Abdulla Watad, Nicola Luigi Bragazzi, Dennis Mcgonagle, Doron Comanesther, Arnon Cohen, Howard Amital
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Familial Mediterranean fever (FMF) is a common, hereditary autoinflammatory disorder, caused by mutations in the MEFV gene encoding for pyrin. MEFV mutations have been also reported in spondyloarthritis (SpA)-associated disorders including Crohn's disease, ulcerative colitis, Behçet's disease, psoriasis and ankylosing spondylitis (AS) with the latter 3 disorders considered under the umbrella term of "MHC-I-opathies" due to population-level associations of HLA-B51, Cw0602 and HLA-B27, respectively. FMF and the SpA group of disorders share an association with disease localization to site of physical stress or microdamage with innate immune activation at such sites as a primary driver of immunopathology but this is not the case for classical autoimmune diseases where central tolerance failure is an overarching immunological concept.. <h3>Objectives</h3> To test the hypothesis that autoinflammation in FMF may exaggerate the tendency towards adaptive immunopathology or MHC class-I associated disorders and therefore a higher prevalence of SpA-related disorders in patients with FMF. <h3>Methods</h3> 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 sarcoidosis, pernicious anaemia, pemphigus vulgaris, and myasthenia gravis 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. <h3>Results</h3> FMF showed a strong association with MHC class I related diseases: OR 28.58 ([95%CI 6.93-117.87], p&lt;0.0001) for Behçet's disease, OR of 10.33 ([95%CI 4.09-26.09], p&lt;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&lt;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 strongly MHC class II-associated including pemphigus vulgaris, sarcoidosis, pernicious anaemia and myasthenia gravis. At the Cox multivariate survival analysis, the mortality of FMF patients was higher only in Crohn's disease with an HR of 2.32 ([95%CI 1.09-4.93], p=0.0291). <h3>Conclusion</h3> FMF patients are associated with increased risk of SpA-related disease diagnosis including MHC-I-opathies suggesting that tissue-specific dysregulation of innate immunity share between FMF and SpA spectrum disorders may drive adaptive immune MHC class I associated conditions. <h3>Disclosure of Interests</h3> Abdulla Watad: None declared, Nicola Luigi Bragazzi: None declared, Dennis McGonagle Consultant for: Lilly, Novartis UCB, Speakers bureau: Lilly, Novartis UCB, Doron Comanesther: None declared, Arnon Cohen Grant/research support from: Prof. Arnon Cohen received research grants from Janssen, Novartis and AbbVie and Sanofi, Consultant for: Prof. Arnon Cohen served as a consultant, advisor for AbbVie; Amgen; Boehringer Ingelheim; Dexcel pharma; Janssen, Lilly; Neopharm; Novartis, Perrigo; Pfizer; Rafa; Sanofi, Speakers bureau: Prof. Arnon Cohen served as speaker for AbbVie; Amgen; Boehringer Ingelheim; Dexcel pharma; Janssen, Lilly; Neopharm; Novartis, Perrigo; Pfizer; Rafa; Sanofi, Howard Amital Grant/research support from: Pfizer, AbbVie, Janssen, Grant/research support from: Pfizer, AbbVie, Janssen, Consultant for: Pfizer, Merck Sharp &amp; Dohme, Consultant for: Pfizer, Merck Sharp &amp; Dohme, Speakers bureau: Pfizer, Merck Sharp &amp; Dohme, Janssen, Sanofi, Bristol-Myers Squibb, Abbvie, Neopharm, Speakers bureau: Pfizer, Merck Sharp &amp; Dohme, Janssen, Sanofi, Bristol-Myers Squibb, Abbvie, Neopharm