Influence of HLA-DR alleles on rheumatoid arthritis: susceptibility and severity in Argentine patients

To determine the frequency of shared epitopes in our population of patients with rheumatoid arthritis (RA) and to investigate whether the presence of these alleles is associated with a more aggressive form of disease.

Demographic and clinical data were obtained from 140 patients with RA, 123 female, mean age 49.9+/-11.7 years and mean disease duration 9.4+/-6.3 years. Radiographs of both hands were taken and scored by Larsen's method. HLA-DR alleles were determined by PCR-SSP. The control group comprised 202 healthy ethnic-matched subjects.

DR4 was significantly more frequent in patients with RA than controls, and was observed in 70/140 patients (50%) versus 47/202 controls (23.27%) (odds ratio 3.25, CI 1.99-5.35, Pcorr 5 x 10(-5)). Within DR4 subtypes *0404 and *0401 were the most commonly found (37.7 and 29%, respectively). DR3 and DR11 exerted a protective effect with significantly higher frequency in controls than in patients with RA. When patients were divided into 2 groups according to disease severity (radiographic score) the frequency of alleles with QKRAA and QRRAA sequences was similar in both groups. Although with lower frequency, subtype *1001 alone was significantly more frequent in the severe-condition group [7 (13.5%) vs 3 (3.4%), p = 0.03].

These results are in accordance with findings observed in Caucasians and differ from other Latin American populations. However shared epitope alleles failed to correlate with more severe disease with the exception of subtype *1001 which, although infrequent, was significantly more frequent in patients with relevant radiological damage.