Hall P J, Burman S J, Laurent M R, Briggs D C, Venning H E, Leak A M, Bedford P A, Ansell B M
Ann Rheum Dis. 1986 Jun;45(6):464-74. doi: 10.1136/ard.45.6.464.
To investigate the genetics of susceptibility to early onset pauciarticular juvenile chronic arthritis (JCA), 158 unrelated ethnic British patients with a mean disease onset of 3.2 years, together with controls, were tested for HLA-A, B, C, and DR antigens. Additionally, 117 patients were also investigated for complement Bf and C4 markers. New observations included an increased frequency of the C4B 2 allotype (p corrected (pc) less than 0.02) and C4A 4,B 2 phenotype (p less than 0.0005). Findings suggested a unique increase of the haplotype HLA-DRw8, BfS, C4A4, C4B*2, HLA-B39, possibly predisposing to more severe disease. Strong positive associations were confirmed with HLA antigens A2 (pc = 2.5 X 10(-8)), DRw8 (pc = 3.5 X 10(-14)), DR5 (pc less than 0.02), DRw52 (pc = 2.8 X 10(-6)) and DR5, w8 phenotype (pc = 3.9 X 10(-6)), and negative associations with DR7 (pc = 5.8 X 10(-7)), DR4 (pc less than 0.002), and DRw53 (pc = 0.004). Antinuclear antibody (ANA) seropositivity correlated with DR5 (p less than 0.02), and in children with chronic iridocyclitis (CIR) Bw62 incidence was raised (p less than 0.03) and B44 reduced (p less than 0.03). HLA-A2 was found in 88% of ANA+, CIR+ patients (p less than 0.01). A significant excess of DR5, w8 heterozygotes was present (relative risk = 41.1) and a lack of corresponding homozygotes. Results are inconsistent with a recessive, dominant, or intermediate mode of inheritance of susceptibility, and favour the existence of at least two DR linked 'disease' genes. Moreover, there may be an interaction in heterozygotes of combinatorial factors associated with DR5 and DRw8 in enhancing susceptibility. Possible immunogenetic mechanisms underlying the observed associations with three antigen classes are discussed. Evidence here suggests a role for the HLA-DQ locus in determining susceptibility to this disease.
为了研究早发性少关节型幼年慢性关节炎（JCA）易感性的遗传学，对158名平均发病年龄为3.2岁的无亲缘关系的英国种族患者以及对照组进行了HLA - A、B、C和DR抗原检测。此外，还对117名患者进行了补体Bf和C4标记物的研究。新的观察结果包括C4B 2同种异型（校正P值（pc）小于0.02）和C4A 4，B 2表型（P小于0.0005）的频率增加。研究结果表明单倍型HLA - DRw8、BfS、C4A4、C4B*2、HLA - B39出现独特增加，可能易患更严重的疾病。证实与HLA抗原A2（pc = 2.5×10^(-8)）、DRw8（pc = 3.5×10^(-14)）、DR5（pc小于0.02）、DRw52（pc = 2.8×10^(-6)）和DR5，w8表型（pc = 3.9×10^(-6)）呈强正相关，与DR7（pc = 5.8×10^(-7)）、DR4（pc小于0.002）和DRw53（pc = 0.004）呈负相关。抗核抗体（ANA）血清阳性与DR5相关（P小于0.02），在患有慢性虹膜睫状体炎（CIR）的儿童中，Bw62发生率升高（P小于0.03），B44降低（P小于0.03）。在88%的ANA阳性、CIR阳性患者中发现了HLA - A2（P小于0.01）。存在显著过量的DR5，w8杂合子（相对风险 = 41.1）且缺乏相应的纯合子。结果与易感性的隐性、显性或中间遗传模式不一致，支持至少存在两个与DR连锁的“疾病”基因。此外，在增强易感性方面，与DR5和DRw8相关的组合因子杂合子之间可能存在相互作用。讨论了与三类抗原相关的观察到的关联背后可能的免疫遗传机制。此处的证据表明HLA - DQ基因座在决定对该疾病的易感性中起作用。
