Etiopathogenic role of HLA-B27 alleles in ankylosing spondylitis

Akkoc N., Khan M. A.

APLAR Journal of Rheumatology, vol.8, no.3, pp.146-153, 2005 (Scopus) identifier

  • Publication Type: Article / Review
  • Volume: 8 Issue: 3
  • Publication Date: 2005
  • Doi Number: 10.1111/j.1479-8077.2005.00152.x
  • Journal Name: APLAR Journal of Rheumatology
  • Journal Indexes: Scopus, Academic Search Premier
  • Page Numbers: pp.146-153
  • Keywords: Alleles, Ankylosing spondylitis, Etiopathogenesis, Genetics, HLA-B27, Polymorphisms, Spondyloar, Subtypes, Thropathies
  • Dokuz Eylül University Affiliated: Yes


HLA-B27 is the major genetic susceptibility factor for ankylosing spondylitis (AS). However, its precise role in the pathogenesis of AS still remains unclear, even though its gene has been cloned and sequenced, and its crystallographic structure has been defined. Arthritogenic peptide and molecular mimicry hypotheses propose mechanisms related to an antigen-presenting function of HLA-B27 to be responsible for disease development. However, peculiar aspects of its immunobiology, such as its misfolding and heavy chain dimerization raise the possibility of involvement of pathogenic mechanisms unrelated to its physiological function. Moreover, HLA-B27 is not a single allele, but a family of 31 different alleles, named HLA-B*2701 to HLA-B*2727. Studies worldwide indicate that the relatively common alleles (subtypes) HLA-B*2705, B*2704, and B*2702 are strongly associated with AS, whereas HLA-B*2706 which is prevalent in South-east Asia and HLA-B*2709 which is prevalent on the Italian island of Sardinia, seem to lack such an association. The distinction between the disease-associated subtypes and those that are not associated, may provide clues to the actual role of HLA-B27 in disease pathogenesis. B*2706 differs from B*2704 by only two residues, and B*2709 differs from B*2705 by only one residue. Moreover, both B*2706 and B*2709 bind an endogenous peptide (derived from vasoactive intestinal peptide type 1 receptor) and also an exogenous peptide (latent membrane protein 2 of Epstein-Barr virus) but in two drastically diverse conformations. These recent X-ray diffraction studies of individual peptides in the context of different HLA-B27 alleles broaden our perception of the possible pathogenetic role of this molecule in the development of AS and related spondyloarthopathies. In summary, the pathogenetic role of HLA-B27 in AS seem to be quite heterogenous, and cannot be explained by a single mechanism, and new ideas have been raised based on the aberrant immunobiologic features of HLA-B27. ©Asia Pacific League of Associations for Rheumatology.