Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Japan.
Ann Rheum Dis. 2011 Dec;70(12):2134-9. doi: 10.1136/annrheumdis-2011-200353. Epub 2011 Aug 27.
HLA-DRB1 is associated with rheumatoid arthritis (RA). However, it has recently been suggested that HLA-DRB1 is only associated with patients with RA who have anticitrullinated peptide/protein antibodies (ACPA), which are specific to RA.
To elucidate whether specific HLA-DR alleles are associated with ACPA-negative RA development.
HLA-DRB1 typing was carried out in 368 Japanese ACPA-negative patients with RA and 1508 healthy volunteers as the first set, followed by HLA-DRB1 typing of 501 cases and 500 controls as the second set. The HLA-DRB1 allele frequency and diplotype frequency were compared in each group, and the results of the two studies were combined to detect HLA-DRB1 alleles or diplotypes associated with ACPA-negative RA.
HLA-DRB112:01 was identified as a novel susceptibility allele for ACPA-negative RA (p=0.000088, OR=1.72, 95% CI 1.31 to 2.26). HLA-DRB104:05 and 14:03 showed moderate associations with ACPA-negative RA (p=0.0063, OR=1.26, 95% CI 1.07 to 1.49 and p=0.0043, OR=1.81, 95% CI 1.20 to 2.73, respectively). The shared epitope was weakly associated with ACPA-negative RA, but no dosage effect was detected (p=0.016, OR=1.17, 95% CI 1.03 to 1.34). A combination of HLA-DRB112:01 and DRB109:01 showed a strong association with susceptibility to ACPA-negative RA (p=0.00013, OR=3.62, 95% CI 1.79 to 7.30). Homozygosity for HLA-DR8 was significantly associated with ACPA-negative RA (p=0.0070, OR=2.16, 95% CI 1.22 to 3.82). It was also found that HLA-DRB115:02 and *13:02 were protective against ACPA-negative RA (p=0.00010, OR=0.68, 95% CI 0.56 to 0.83 and p=0.00059, OR=0.66, 95% CI 0.52 to 0.84, respectively).
In this large-scale association study multiple alleles and diplotypes were found to be associated with susceptibility to, or protection against, ACPA-negative RA.
HLA-DRB1 与类风湿关节炎（RA）相关。然而，最近有人提出 HLA-DRB1 仅与具有针对 RA 的抗瓜氨酸肽/蛋白抗体（ACPA）的 ACPA 阴性 RA 患者相关，而 ACPA 是 RA 的特异性抗体。
阐明特定的 HLA-DR 等位基因是否与 ACPA 阴性 RA 的发展相关。
在第一组中，对 368 例日本 ACPA 阴性 RA 患者和 1508 名健康志愿者进行 HLA-DRB1 分型，随后对 501 例病例和 500 例对照进行 HLA-DRB1 分型。比较每组 HLA-DRB1 等位基因频率和二倍体频率，并将两项研究的结果合并，以检测与 ACPA 阴性 RA 相关的 HLA-DRB1 等位基因或二倍体。
鉴定出 HLA-DRB112:01 是 ACPA 阴性 RA 的新型易感等位基因（p=0.000088，OR=1.72，95%CI 1.31 至 2.26）。HLA-DRB104:05 和 14:03 与 ACPA 阴性 RA 呈中度相关（p=0.0063，OR=1.26，95%CI 1.07 至 1.49 和 p=0.0043，OR=1.81，95%CI 1.20 至 2.73）。共享表位与 ACPA 阴性 RA 相关，但未检测到剂量效应（p=0.016，OR=1.17，95%CI 1.03 至 1.34）。HLA-DRB112:01 和 DRB109:01 的组合与 ACPA 阴性 RA 的易感性具有很强的关联（p=0.00013，OR=3.62，95%CI 1.79 至 7.30）。HLA-DR8 的纯合性与 ACPA 阴性 RA 显著相关（p=0.0070，OR=2.16，95%CI 1.22 至 3.82）。还发现 HLA-DRB115:02 和 *13:02 对 ACPA 阴性 RA 具有保护作用（p=0.00010，OR=0.68，95%CI 0.56 至 0.83 和 p=0.00059，OR=0.66，95%CI 0.52 至 0.84）。
在这项大规模的关联研究中，发现多个等位基因和二倍体与 ACPA 阴性 RA 的易感性或保护作用相关。
