HLA antigen associations with extra‐articular rheumatoid arthritis

Abstract

Seventy-seven patients with rheumatoid arthritis were investigated to examine the frequency of HLA antigens and their relationship to clinical and serological manifestations of extra-articular disease. The phenotype frequencies of DR4, DRw53, Bw62 and Cw3 were significantly increased, compared to normal controls, and there were negative associations with DR2 and DR7. The HLA antigen in strongest association with rheumatoid arthritis was DR4 (73.6%) and the relationship with DRw53 appeared to be secondary. The frequency of DR4 rose to 92% in seropositive patients with extra-articular disease manifestations whose serum contained immune complexes. A high frequency of DR4 was also seen in male patients (86%), reaching 100% in the small group of seropositive male patients with immune complexes. It is suggested that extra-articular disease represents a manifestation of severe classical rheumatoid arthritis and is not an 'overlap' syndrome. We propose that the HLA haplotype Cw3-Bw62-Dw4-DR4-DRw53 makes a greater genetic contribution to disease susceptibility in both extra-articular and male rheumatoid arthritis patients than in other subsets of RA.

Association of tumor necrosis factor microsatellite polymorphisms with HLA‐DRB1*04–bearing haplotypes in rheumatoid arthritis patients

“…This may explain our earlier observations that suggested an association of this haplotype with specific disease features (28). The possibility that the DRBl*O401;B44 haplotype also encodes a preset level for the production of TNFa should now be carefully examined, although the study by Pociot et a1 (21) suggests that the level may not be as high as for TNFaZbearing haplotypes.…”

“…This may be of particular relevance because previous studies have documented an HLA-DRB1*04;B62 haplotype in RA patients, and this haplotype is associated with the risk of developing extraarticular disease and RA in males (28). Given the fact that age and sex influence the HLA-DR associations with RA (12), it would be interesting to study a large enough cohort of RA patients to allow stratlfcation, in order to explore TNF associations.…”

HLA–DRB1 and persistent chronic inflammation contribute to cardiovascular events and cardiovascular mortality in patients with rheumatoid arthritis

“…These alleles encode a conserved amino acid sequence (QKRAA, QRRAA, or RRRAA), called the shared epitope, at position 70 -74 in the third hypervariable region of the HLA-DR␤1 molecule (16). A number of studies have shown an association between HLA-DRB1*04 shared epitope alleles and extraarticular disease in patients with RA from different populations (17)(18)(19)(20). Also, regarding medication, patients with RA from northwest Spain requiring treatment with cyclosporin A because of severe disease and incomplete response to methotrexate (MTX) were significantly more likely to have HLA-DRB1*04 shared epitope alleles than patients not requiring such treatment (21).…”

Bf and C3 Polymorphisms in Rheumatoid Arthritis

“…The status of RA as a disease in which susceptibility is influenced by genetic fac tors, at least when severe disease is taken into account, is well established [Panayi et al, 1978;Jones et at., 1983: Ollier et al, 1984. In European populations HLA DR4 has been consistently shown to be more prevalent in patient groups than in controls, although there is controversy over whether or not DR4 is a marker for severe disease as measured by parameters such as the presence of RF, rheumatoid nodules and/or bony erosions.…”