Inherited predisposition to iridocyclitis with juvenile rheumatoid arthritis: selectivity among HLA-DR5 haplotypes.

Abstract

HLA-DR5 is associated with a chronic iridocyclitis and juvenile rheumatoid arthritis with onset in early childhood. Previously published data provided indirect evidence for selective linkage between two HLA-B alleles and HLA-DR5. To test this observation further, 38 families, the probands of which have chronic iridocyclitis and juvenile rheumatoid arthritis, were HLA typed so that haplotypes associated with disease could be established. HLA-DR5 was linked to HLA-Bw44 or to HLA-Bw35 and to HLA-Cw4 in the majority of haplotypes obtained in the probands. Both HLA-Bw44, -DR5 and HLA-Bw35, -Cw4, -DRS occurred more commonly in the proband haplotypes than in the control haplotypes. The frequency of the haplotype HLA-Bw44, -DRS was 0.133 compared with 0.007 (X2 = 27.04, P < 10-6) and for HLA-Bw3S, -Cw4, -DRS, it was 0.093 compared with 0.11 (X2 = 13.83, P = 0.0002). The relative risks were 20.77 and 9.23, respectively, versus 3.52 for HLA-DRS alone. HLA-Bw44 occurred much more commonly in proband HLA-DR5 haplotypes (0.455) compared with control HLA-DR5 haplotypes (0.067) (X2 =

Juvenile chronic arthritis—clinical sub-groups with particular relationship to adult patterns of disease

“…Despite a correlation between ANA positivity and DRw8 and the known association between chronic iridocyclitis and ANA, the multicentre study failed to detect significant differences in the frequency of DR5 and/or DRw8 in those with iridocyclitis. This is in contrast to previous work demonstrating that not only is DR5 increased in those with eye disease but that specific DR5-bearing haplotypes (Bw44 or Bw35, Cw4) predispose to this complication (Miller et al, 1984). It is anticipated that on-going international collaboration will enable further clarification of these associations.…”

Juvenile rheumatoid arthritis as a complex genetic trait

“…Family-based controls are a more appropriate approach when population stratification is a possibility, reducing the ethnicity issues (69). Family-based methodology has been employed in association studies using a pool of familial nonproband HLA haplotypes as controls and in TDTs (62,70).…”

Juvenile Idiopathic Arthritis-Associated Uveitis: Clinical Features and Complications, Risk Factors for Severe Course, and Visual Outcome

“…7 In addition to oligoarticular onset, additional risk factors for the development of uveitis among patients with JIA include younger age of onset (4 years), female sex, the presence of circulating antinuclear antibodies (ANA), HLA associations (HLA-DR5, HLA-DRB1*13), and, most recently, antihistone antibodies as possible biomarkers for chronic uveitis ( Table 1). [8][9][10][11][12][13] In a recent retrospective study of 1047 patients with JIA, the risk of the development of uveitis was age dependent in girls but not for boys: 37% for girls age 1-2 years vs. 7% for boys in the same age range. 14 Similarly, the risk of uveitis was maximal at 47% among girls and 10% for boys aged 1-2 years who were ANA positive at the time of the onset of JIA.…”