Early-onset pauciarticular juvenile rheumatoid arthritis associated with human leukocyte antigen-DRw5, iritis, and antinuclear antibody

Abstract

Evidence has been sought for a genetically determined predisposition among children with juvenile rheumatoid arthritis (JRA) who are also at particular risk for the development of inflammatory eye disease. 45 unrelated Caucasian patients (41 female) with early-onset pauciarticular JRA were human leukocyte antigen (HLA) typed. 28 of the study group were found to be HLA-DRw5 compared with 16 of 84 controls (X2, 24.3, P = < 0.001). 9 patients were HLA-DRw8 compared with 4 of 84 controls (X2, 7.51, P = < 0.01). Iritis developed in 24 of the 45 children studied, 17 of whom were typed as HLA-DRw5 when compared to controls (X2, 26.76, P = < 0.001) and 6 with iritis typed as HLA-DRw8 (X2, 9.10, P = <0.01). Antinuclear antibody was found in the serum of 17 of the 28 patients typing as HLA-DRw5 compared with 4 of the 17 who did not have this antigen (X2, 5.88, P = <0.02). No such association was seen in patients with HLA-DRw8. In a study of linked genes, a delta value of 0.090 was found for HLA-DRw5 with HLA-B12, of 0.070 for DRw5 with HLA-Cw4, and a value of 0.050 for DRw5 and HLA-Bw45. This suggests a linkage disequilibrium between HLA-DRw5 and these two B series alleles, a conclusion which was supported by haplotype analysis in families of 11 of these disease probands. HLA-DRw5 has not previously been reported to be increased in any rheumatic disease group. It is proposed that HLA-DRw5 is a genetic marker defining those at risk for early-onset pauciarticular JRA with iritis.