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An update on the contribution of the MHC to as susceptibility

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Abstract

The 40-year-old association of HLA-B27 with ankylosing spondylitis is one of the best examples of disease association with a hereditary marker. Genomewide association and family studies suggest that other important major histocompatibility complex (MHC) influences are operative in ankylosing spondylitis (AS) susceptibility. HLA-B27 positive hepatitis C individuals are immunologically more efficient in combating viral infections such as HIV-1, hepatitis C, and influenza and less efficient in combating against certain bacteria (and perhaps other organisms) capable of surviving intracellularly. A recent representative population survey of the frequency of HLA-B27 in the USA found a lower frequency of HLA-B27 in older US adults, perhaps reflecting this. Other HLA class I and class II alleles have been implicated in AS susceptibility, the most consistent being HLA-B*40/B60 (B*40:01) but also B14, B15, A*0201, DRB1*04:04, and certain DPA1 and DPB1 alleles. Non-HLA MHC alleles have also been implicated, although many such studies have been inconsistent, likely due to power issues related to the low number of HLA-B27-negative AS patients examined. The best evidence is for major histocompatibility complex class I chain-related gene A (MICA) whose recognition by intestinal epithelial T cells expressing different V-delta-1 gamma/delta TCR further implicates the gut in AS pathogenesis. The HLA class I and class II and other non-HLA allelic associations underscore the importance of T cells in AS pathogenesis.

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Acknowledgments

This work was supported by the National Institutes of Health-National Institute of Allergy and Infectious Diseases (NIH-NIAIS) grant UO1 AI09090, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIH-NIAMS) grants R01 AR-46208 and 2P01AR052915-06A1, and by University Clinical Research Grants M01-RR-02558 (The University of Texas Health Science Center at Houston.

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  1. Division of Rheumatology and Clinical Immunogenetics, The University of Texas Health Science Center at Houston, MSB 5.270, 6431 Fannin, Houston, TX, 77030, USA

    John D. Reveille

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Correspondence to John D. Reveille.

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Reveille, J.D. An update on the contribution of the MHC to as susceptibility. Clin Rheumatol 33, 749–757 (2014). https://doi.org/10.1007/s10067-014-2662-7

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