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'MHC-I-opathy'—unified concept for spondyloarthritis and Behçet disease

Nature Reviews Rheumatology volume 11, pages 731–740 (2015)Cite this article

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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.

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Figure 1: Tissue specificity in the MHC-I-opathies.
Figure 2: Adaptive immune priming in the MHC-I-opathies.
Figure 3: The IL-23 axis and innate lymphoid cells in target tissues affected by MHC-I-opathies.
Figure 4: Secondary innate immune amplification in the MHC-I-opathies.

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Acknowledgements

D.M.'s work is supported by the NIHR (National Institute of Health Research) Leeds Biomedical Research Unit. A.G.'s work is supported by Istanbul University Research Fund.

Author information

Authors and Affiliations

  1. Section of Musculoskeletal Diseases, The Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and Chapel Allerton Hospital, Chapeltown Road, Leeds, LS7 4SA, West Yorkshire, UK

    Dennis McGonagle

  2. Division of Rheumatology, University of Ottawa, Arthritis Center, 1967 Riverside Drive, Ottawa, K1H 7W9, ON, Canada

    Sibel Zehra Aydin

  3. Department of Internal Medicine, Division of Rheumatology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turgut Ozal Millet Caddesi, Istanbul, 34093, Fatih, Turkey

    Ahmet Gül

  4. Department of Internal Medicine, Hospital Saint-Louis, University Paris 7–Diderot, Paris, 1 Avenue Claude-Vellefaux, Paris Cedex 10, 75475, France

    Alfred Mahr

  5. Department of Internal Medicine, Division of Rheumatology, Marmara University, School of Medicine, Mimar Sinan Caddesi 41, Istanbul, 34890, Pendik, Turkey

    Haner Direskeneli

Authors
  1. Dennis McGonagle
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  2. Sibel Zehra Aydin
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  3. Ahmet Gül
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  4. Alfred Mahr
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  5. Haner Direskeneli
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Contributions

All authors contributed to researching data for the article, discussions of its content, writing the article, and review or editing of the manuscript before submission.

Corresponding author

Correspondence to Dennis McGonagle.

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Competing interests

The authors declare no competing financial interests.

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McGonagle, D., Aydin, S., Gül, A. et al. 'MHC-I-opathy'—unified concept for spondyloarthritis and Behçet disease. Nat Rev Rheumatol 11, 731–740 (2015). https://doi.org/10.1038/nrrheum.2015.147

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