New insights regarding HLA‐B27 diversity in the Asian population

Abstract

A polymerase chain reaction-sequence-specific primer (PCR-SSP) method which distinguishes all B27 alleles described at present (B*2701-23) has been developed. The distribution of B27 alleles was characterised in six different Asian populations. HLA-B*2705, 02, 04, 07, 22 (formerly B*2706) subtypes found in Asian populations differ in their ethnic distribution, which may be the result of different genetic and geographic origins. Furthermore, two novel B27 alleles were found in this study. B*2714 was identified in two Siberians, one of whom was a patient with ankylosing spondylitis. B*2715 was found in two patients with ankylosing spondylitis in Thais. These associations have not previously been reported in either ethnic group.

The Peptide Repertoires of HLA-B27 Subtypes Differentially Associated to Spondyloarthropathy (B*2704 and B*2706) Differ by Specific Changes at Three Anchor Positions

“…B*2706 has been found with significant frequency in Southeast Asia and the Pacific and at much lower frequency in continental China. A population study carried out in Thailand initially showed that whereas B*2704 was strongly linked to AS in this population, no B*2706 AS patients could be found, despite the significant frequency of this allele among healthy controls (13,17). This differential association of B*2704 and B*2706 in a same population was subsequently confirmed in two additional studies carried out in Indonesia (14) and among Singapore Chinese (15).…”

“…Two B*2706-positive AS patients were found in China (12), suggesting that lack of association of this subtype with AS is not absolute and might be modulated to some extent by additional genetic factors. However, the very low frequency of B*2706 in China has thus far precluded case-control or family segregation studies in these populations (17). B*2704 and B*2706 differ by only two amino acid changes: H114D and D116Y (19 -21).…”

Allospecific T Cell Epitope Sharing Reveals Extensive Conservation of the Antigenic Features of Peptide Ligands Among HLA-B27 Subtypes Differentially Associated with Spondyloarthritis

“…Among the large body of indirect evidence in support of this idea are reports that several HLA-B27 allotypes (B*2702, B*2704, B*2705, B*2707) are strongly associated to AS, whereas B*2706 and B*2709 are weakly or not associated (2)(3)(4)(5)(6)(7). This is suggestive of peptide involvement in the pathogenesis of Spa because subtypes differentially associated to AS differ only by one (B*2705/B*2709) or two (B*2704/B*2706) amino acid changes that are located in the peptide binding site and influence peptide specificity (8 -10).…”

Characterization of a Proteasome and TAP-independent Presentation of Intracellular Epitopes by HLA-B27 Molecules

“…HLA-B27 includes a number of alleles that differ from each other in one or a few amino acids, and some of them, located in the peptide binding groove, have been proven to be functionally relevant. Noteworthy, some of these alleles such as the B*2709 in Sardinia (12,13) and the B*2706 in Asia (14), are not associated with AS since they have not been reported, except anecdotically, in patients, and therefore have become a powerful tool to gain insights into disease association. Functional differences between AS-associated and non-AS-associated B27 subtypes (15), B27 transgenic animal models (16) and a recent report showing an association between AS and ERAP1 (17), an ER aminopeptidase trimming the peptides presented by the HLA-class I molecules, strongly suggest a direct role for the HLA-B27 molecules in disease pathogenesis, possibly presenting tissue-specific peptides (18).…”