SUMMARY Toinvestigate thegenetics ofsusceptibility toearly onsetpauciarticular juvenile chronic arthritis (JCA), 158unrelated ethnic British patients witha mean disease onsetof3-2 years,together withcontrols, were tested forHLA-A,B,C,andDR antigens. Additionally, 117 patients were also investigated forcomplement BfandC4markers. Newobservations included anincreased frequency oftheC4B2allotype (pcorrected(pc) <0.02) andC4A4,B2phenotype (p<O-0005). Findings suggested a unique increase ofthehaplotype HLA-DRw8,Bf*S, C4A*4, C4B*2,HLA-B39, possibly predisposing tomore severedisease. Strong positive associations wereconfirmed withHLA antigens A2(pc=2-5 x10-8), DRw8 Pc=3-5x 10-'14), DR5(pc<0 02), DRw52(pc=2 8x10-6) andDR5,w8phenotype (pc=3.9X 10-),andnegative associations with DR7(pc=5-8x10-7), DR4(pc<0002), andDRw53(Pc=0004). Antinuclear antibody (ANA) seropositivity correlated withDR5 (p<002), andinchildren withchronic iridocyclitis (CIR) Bw62incidence was raised (p<003) andB44reduced (p<003). HLA-A2was foundin88%of ANA+, CIR+patients (p<0-01). A significant excessofDR5,w8heterozygotes was present (relative risk=41.1) anda lackofcorresponding homozygotes. Results areinconsistent witha recessive, dominant, or intermediate modeofinheritance ofsusceptibility, andfavour the existence ofatleast twoDR linked 'disease' genes.MoreoVer, there may bean interaction in heterozygotes ofcombinatorial factors associated withDR5 andDRw8inenhancing susceptibility. Possible immunogenetic mechanisms underlying theobserved associations withthree antigen classes are discussed. Evidence heresuggests a rolefortheHLA-DQ locusin determining susceptibility tothisdisease.
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