HLA in ankylosing spondylitis: is HLA-B27 the only MHC gene involved in disease pathogenesis?

Semin Arthritis Rheum. 1994 Apr;23(5):295-309. doi: 10.1016/0049-0172(94)90026-4.


Linkage analysis of HLA haplotypes, HLA-B27 subtypes, and a 9.2-kb PvuII B7 restriction fragment length polymorphism (RFLP) (shown previously to be associated with peripheral arthritis in ankylosing spondylitis [AS]) in 115 relatives from 12 multiplex spondyloarthropathy (SNSA) and 2 B27-positive control families showed AS to be linked to HLA-B27 haplotypes. The RFLP segregated with HLA-A3- and HLA-A9-bearing haplotypes (lod score, 10.98; odds in favor of linkage, 9.2 x 10(10):1), although its linkage to AS or other SNSA per se was not seen. The association of HLA-A3/A9 with the RFLP was also seen in 52 AS patients and 92 controls, although no HLA-A, -B, -C, or -DR allele (other than HLA-B27) was significantly increased in frequency. The HLA-B27 subtype seen on all but one of the haplotypes studied was B*2705, the sole exception being HLA-B*2702. Although not ruling out a second HLA-A-linked gene influencing the clinical expression of AS, these data fail to support the role of a second MHC-associated gene in the pathogenesis of AS per se.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Chromosome Mapping
  • DNA / genetics
  • Family Health
  • Female
  • Gene Frequency
  • Genes, MHC Class I / physiology*
  • Genetic Linkage
  • HLA Antigens / analysis
  • HLA Antigens / genetics
  • HLA Antigens / physiology*
  • HLA-A Antigens / analysis
  • HLA-A Antigens / genetics
  • HLA-A Antigens / physiology
  • HLA-B27 Antigen / analysis
  • HLA-B27 Antigen / genetics
  • HLA-B27 Antigen / physiology*
  • Humans
  • Male
  • Pedigree
  • Polymorphism, Restriction Fragment Length
  • Spondylitis, Ankylosing / etiology*
  • Spondylitis, Ankylosing / genetics
  • Spondylitis, Ankylosing / immunology


  • HLA Antigens
  • HLA-A Antigens
  • HLA-B27 Antigen
  • DNA