Distribution of HLA-B27 subtypes in patients with ankylosing spondylitis: the disease is associated with a common determinant of the various B27 molecules.

Abstract

SUMMARY HLA-B27 subtypes can be defined by cellular, serological, and biochemical techniques. The seven subtypes4 9 So far identified represent structural variants of B27 with limited variations in the amino acid sequence of the B27 molecule. The routinely typed B27 'antigen' remains a common (shared, public) determinant present on various B27 molecules. The distribution of the subtypes varies strongly among different ethnic groups and they occur in different linkage disequilibria.4 In the healthy Dutch population only two subtypes were found: B27W (B27*1, B27M2+) (90%) and B27K (B27-2, B27M2-) (10%). A similar distribution of B27 subtypes was observed in 91 unrelated Dutch patients with ankylosing spondylitis (AS)-namely, 92% B27W and 8% B27K. In Oriental populations the subtype distribution is quite different: B27W occurs in less than 50%, whereas more than 50% individuals are of the B27C and B27D subtypes. Preliminary data indicate that the distribution of subtypes in healthy and diseased Oriental individuals is similar. These results suggest that the B27 and disease (AS) association is not correlated with the structural variations of one of the B27 subtypes, but with a common B27 determinant shared by various B27 subtypes. Consequently, the disease is older than the B27 variants. Further studies on disease and subtype distribution in various ethnic groups might contribute to a better understanding of the origin of both.

In vitro mutagenesis of HLA-B27. Substitution of an unpaired cysteine residue in the alpha 1 domain causes loss of antibody-defined epitopes.

“…Because class I MHC molecules serve as recognition elements for CTL, and because only a small minority of HLA-B27' individuals ever develop B27-associated disease (7,32,33), efforts have been made to identify CTL-defined B27 subtypes that correlate specifically with disease. However, no significant correlation has been found between AS and any particular subtype of B27 (7,9,34), and AS remains most highly correlated with serologically defined B27, just as originally reported in 1973 (9,35,36).…”

“…Although it remains formally possible that this association is due to an allele in tight linkage disequilibrium with HLA-B27, there is now substantial indirect evidence that the HLA-B27 molecule itself is directly involved in disease pathogenesis (7,9). The six B27 subtypes identified by isoelectric focusing have been sequenced at the protein level (5,6) and shown to display distinctive cytolytic T cell (CTL)-defined epitopes (5,30,31).…”

“…The strongest association is with AS; in Caucasian populations, the prevalence of HLA-B27 in the general population is -8%, whereas in patients with primary AS it exceeds 90%. Attempts to correlate the incidence of AS with one or more of the B27 subtypes have not been successful; AS apparently is associated with most, if not all, of the B27 subtypes (7,9).…”

Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: getting closer to a cure?

“…Spondyloarthropathies are linked with only some molecular subtypes of HLA-B27. 132 Similar to RA, peptide-binding differences may explain differences in disease susceptibility. HLA-B27 may even present its own B27-derived peptides.…”

HLA-B27 subtypes in the spondarthropathies

“…A previous study, using a combination ol' seroiogical, cellular cytotoxieity. and lEP techniques found that AS patients in the Netherlands had approximately the same subtype distribution as healthy subjects [11]. We determined the B27 subtypes of HLA-B27* AS and ReA patients and of controls from a British population, using a modified immunoprecipitation protocol thai did not require full class 1 HLA typing of subjects.…”