Department of Rheumatology and Clinical Immunology, Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho Sakyo-ku, Kyoto 606-8507, Japan.
Rheumatology (Oxford). 2010 Dec;49(12):2298-304. doi: 10.1093/rheumatology/keq273. Epub 2010 Sep 9.
ACPA is a highly specific marker for RA. It was recently reported that ACPA can be used to classify RA into two disease subsets, ACPA-positive and ACPA-negative RA. ACPA-positive RA was found to be associated with the HLA-DR shared epitope (SE), but ACPA negative was not. However, the suspicion remained that this result was caused by the ACPA-negative RA subset containing patients with non-RA diseases. We examined whether this is the case even when possible non-RA ACPA-negative RA patients were excluded by selecting only patients with bone erosion.
We genotyped HLA-DRB1 alleles for 574 ACPA-positive RA, 185 ACPA-negative RA (including 97 erosive RA) and 1508 healthy donors. We also tested whether HLA-DR SE is associated with RF-negative or ANA-negative RA.
ACPA-negative RA with apparent bone erosion was not associated with SE, supporting the idea that ACPA-negative RA is genetically distinct from ACPA-positive RA. We also tested whether these subsets are based on autoantibody-producing activity. In accordance with the ACPA-negative RA subset, the RF-negative RA subset showed a clearly distinct pattern of association with SE from the RF-positive RA. In contrast, ANA-negative as well as ANA-positive RA was similarly associated with SE, suggesting that the subsets distinguished by ACPA are not based simply on differences in autoantibody production.
ACPA-negative erosive RA is genetically distinct from ACPA-positive RA.
抗环瓜氨酸肽（ACPA）抗体是类风湿关节炎（RA）的高度特异性标志物。最近有研究报道，ACPA 可用于将 RA 分为 ACPA 阳性和 ACPA 阴性 RA 两个疾病亚组。ACPA 阳性 RA 与 HLA-DR 共享表位（SE）相关，但 ACPA 阴性则不然。然而，人们仍然怀疑这一结果是由于 ACPA 阴性 RA 亚组中包含了患有非 RA 疾病的患者所致。我们通过仅选择有骨侵蚀的患者来排除可能的非 RA ACPA 阴性 RA 患者，以检查这种情况是否成立。
我们对 574 例 ACPA 阳性 RA、185 例 ACPA 阴性 RA（包括 97 例侵蚀性 RA）和 1508 例健康供体进行了 HLA-DRB1 等位基因分型。我们还检测了 SE 是否与 RF 阴性或 ANA 阴性 RA 相关。
无明显骨侵蚀的 ACPA 阴性 RA 与 SE 无关，这支持了 ACPA 阴性 RA 在遗传上与 ACPA 阳性 RA 不同的观点。我们还测试了这些亚组是否基于自身抗体产生活性。与 ACPA 阴性 RA 亚组一致，RF 阴性 RA 亚组与 SE 的关联模式明显不同于 RF 阳性 RA。相比之下，RF 阴性和 RF 阳性 RA 与 SE 均具有相似的相关性，这表明通过 ACPA 区分的亚组并非仅仅基于自身抗体产生的差异。
有侵蚀性的 ACPA 阴性 RA 在遗传上与 ACPA 阳性 RA 不同。
