title: 'MHC-I-opathy'-unified concept for spondyloarthritis and Behçet disease.
abstract: The spondyloarthropathies comprise ankylosing spondylitis (AS), reactive arthritis, psoriatic arthritis (PsA) and arthritis associated with inflammatory bowel disease. In this Perspectives article, we describe how Behçet disease and several clinically distinct spondyloarthropathies-all associated with MHC class I (MHC-I) alleles such as HLA-B(*)51, HLA-C(*)0602 and HLA-B(*)27 and epistatic ERAP-1 interactions-have a shared immunopathogenetic basis. As a unifying concept, we propose that barrier dysfunction in environmentally exposed organs such as the skin, and aberrant innate immune reactions at sites of mechanical stress, can often trigger secondary adaptive immune CD8(+) T-cell responses with prominent neutrophilic inflammation that culminate in exacerbation and recurrence of these diseases. Of note, these 'MHC-I-opathies' show a differential immunopathology, probably reflecting antigenic differences within target tissues: HLA-B(*)51 is linked to ocular and mucocutaneous disease but not gut involvement, and HLA-C(*)0602 is linked to type I psoriasis but not scalp or nail disease.
authors.affiliation: Section of Musculoskeletal Diseases, The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and Chapel Allerton Hospital, Chapeltown Road, Leeds, West Yorkshire LS7 4SA, UK.
authors.forename: Dennis
authors.initials: D
authors.lastname: McGonagle
authors.affiliation: Division of Rheumatology, University of Ottawa, Arthritis Center, 1967 Riverside Drive, Ottawa, ON K1H 7W9, Canada.
authors.forename: Sibel Zehra
authors.initials: SZ
authors.lastname: Aydin
authors.affiliation: Istanbul University, Istanbul Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Istanbul, Turgut Ozal Millet Caddesi 34093 Fatih, Istanbul, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Gül
authors.affiliation: Department of Internal Medicine, Hospital Saint-Louis, University Paris 7-Diderot, Paris, 1 Avenue Claude-Vellefaux, 75475 Paris Cedex 10, France.
authors.forename: Alfred
authors.initials: A
authors.lastname: Mahr
authors.affiliation: Marmara University, School of Medicine, Department of Internal Medicine, Division of Rheumatology, Mimar Sinan Caddesi 41, Pendik, 34890, Istanbul, Turkey.
authors.forename: Haner
authors.initials: H
authors.lastname: Direskeneli
mesh_terms: D000818:Animals; D001528:Behcet Syndrome / Q000235:genetics* / Q000276:immunology*; D005805:Genes, MHC Class I; D006801:Humans; D025241:Spondylarthritis / Q000235:genetics* / Q000276:immunology*