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How HLA-B27 Research Landmarks, Advances Relate to Ankylosing Spondylitis Pathogenesis

Joerg Ermann, MD  |  Issue: July 2016  |  

Recent genetic data suggest that AS may be only one example of a group of diseases characterized by epistatic interaction between MHC class I alleles and enzyme variants that affect peptide loading in the ER (MHC I-opathies). The genetic interaction between HLA-B27 and ERAP1 underscores the importance of the MHC class I peptide presentation pathway in the pathogenesis of AS. It favors but does not prove that the arthritogenic/spondylogenic peptide hypothesis is correct because peptide loading will also affect the folding and stability of MHC class I molecules and the specificity of antimicrobial immune responses.

Investigating more broadly the relationship between distinct SpA phenotypes and the various predisposing MHC class I alleles may hold the key to identifying the mechanism underlying the association between HLA-B27 and AS, which has been chased by two generations of researchers since its description in 1973.

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Joerg Ermann, MDJoerg Ermann, MD, is a rheumatologist in the Division of Rheumatology, Immunology, and Allergy at Brigham and Women’s Hospital and Instructor in Medicine at Harvard Medical School. His clinical and research interests are in spondyloarthritis. His lab studies disease mechanisms relevant to spondyloarthritis using mouse models and translational approaches.

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