DNA POLYMORPHISM OF HLA CLASS-II GENES IN PAUCIARTICULAR JUVENILE RHEUMATOID-ARTHRITIS

We investigated the DNA restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) class II genes: HLA-DRB, -DQA, -DQB, DPA, and -DPB in 54 patients with pauciarticular juvenile rheumatoid arthritis (PJRA) and in healthy Danes. The frequencies of DNA fragments associated with the following HLA class II genes were increased in PJRA when compared to normal controls: DRB1*08 (DRw8) (35.2% vs 10.3%, RR = 4.6, p< 10(-3)), DRB3*01/02/03 (DRw52) (76.3% vs 48.1%, RR 3.5, p < 10(-3)), DQA1*0401 (41.0% vs 7.4%, RR = 7.9, p< 10(-3)), DQA1*0501 (55.6% vs 29.7%, RR = 3.0, p < 10(-2), DQB1*0301 (DQw7) (46.2% vs 17.5%, RR = 4.0; p < 10(-2)), DPA1*0201 (44.2% vs 7.9%, RR = 8.7, p < 10(-5)), and DPB1*02 (DPw2) (40.7 % vs 7.1%, RR = 8.5, p < 10(-6)). The frequency of DRB1*11 was not significantly increased. The frequencies of DNA fragments associated with the following HLA class II genes were decreased in PJRA although not statistically significantly so after 'correction' of p values: DRB1*04 (14.8% vs 40.2%, RR = 0.27; p< 10(-3)), DRB1*07 (0% vs 25.9%, RR = 0.04, p< 10(-3)), DRB4*0101 (DRw53) (25.9% vs 53.6%, RR = 0.31, p < 10(-3)), DQA1*0102 (11.6% vs 36.0%, RR = 0.25, p< 10(-4)), and DQA1*0201 (2.6% vs 34.2%, RR = 0.05, p < 10(-2)). Individuals who carried certain combinations of two of the risk factors seemed to have a further increased risk of developing PJRA compared to individuals carrying only one of the risk factors. The combinations of HLA class II genes primarily involved were: DRB1*08 and DQA1*0501, DRB1*08 and DQB1*0301, DRB1*08 and DPA1*0201, DQA1*0401 and DQB1*0301, DQA1*0401 and DPA1*0201, DQA1*0501 and DPA1*0201, and DQA1*0501 and DPB1*02, although other combinations also gave odds ratios which were non-significantly increased compared to the odds ratios of the individual genetic markers. The data suggest that HLA class II gene products coded by genes at different loci interact in the susceptibility of PJRA.