An update on the contribution of the MHC to AS susceptibility.
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.
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@uth.tmc.edu.
John D
JD
Reveille
D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005843:Geography; D015796:HLA-B27 Antigen / Q000235:genetics*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D025241:Spondylarthritis / Q000235:genetics / Q000276:immunology; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000276:immunology; D014481:United States; D055815:Young Adult
D015796:HLA-B27 Antigen