Frequency of the new HLA-B*2709 allele in ankylosing spondylitis patients and healthy individuals.

Abstract

We have recently described a new HLA-B27 subtype, named HLA-B*2709 (Del Porto et al. 1994). This allele is identical to the subtype most frequently found in Caucasoids, HLA-B*2705, except for a single amino acid substitution (Asp to His) in position 116. This residue, that is part of the F pocket of the molecule, has been shown to be relevant in determining which C-terminal amino acid of HLA-class I-binding peptides can be accomodated into the groove (Elliott, 1993). In nonamer peptides, this aminoacid corresponds to a primary anchor position (P9; Madden et al., 1992). Accordingly, we have previously shown that B2709 molecule hardly accepts nonamer peptides with an Arg or Tyr in P9, while the same amino acids represent good anchors for B2705 molecules (Fiorillo et al., 1995). Special attention is focused on HLA-B27 subtypes because of the strong association of B27 with ankylosing spondylitis (AS). More than 90% of AS patients are B27-positive and, conversely, about 4% of B27-positive individuals in the population are affected. This represents a relative risk over 100, that is the highest in HLA-disease associations. However, little is known on the pathogenic mechanisms of the disease. Following the hypothesis that an antigenic B27-binding peptide is involved in the disease (the so-called arthritogenic peptide), differential association with the different B27 subtypes may give a clue on the nature of such peptide. If two subtypes of partially overlapping peptide binding specificity are found to be both AS-associated, this would restrict the search for peptides that can be bound by both allelic products. Conversely, if a B27 subtype is found to be non AS-associated, this would be even more helpful in eliminating an array of peptides as possible candidates.