Clinic of Rheumathology, Azienda Ospedaliero-Universitaria of Udine, Italy.
Autoimmun Rev. 2012 Mar;11(5):315-20. doi: 10.1016/j.autrev.2010.06.012. Epub 2010 Oct 23.
Identification of genetic biomarkers of response to biologics in rheumatoid arthritis (RA) is a relevant issue. Being IL-6 a key cytokine for B cell survival, the interleukin-6 (IL-6) -174G>C and the IL-6 receptor (IL-6R) D358A gene polymorphisms were investigated in 158 RA patients treated with rituximab (RTX). One hundred and twenty-eight (81.0%) were RF positive and 126 (79.7%) were anti-CCP positive. Response to therapy was evaluated at the end of the sixth month after the first RTX infusion, by using both the EULAR and the ACR criteria. The possible relationship with IL-6 serum levels was also studied. By univariate analysis, lack of response by the EULAR criteria was more prevalent in RA patients with the IL-6 -174 CC genotypes (39.1%), than in the GC/GG patients (18.5%) (OR 2.83; 95%CI=1.10-7.27; p=0.031). A good response was noticed in only one patient (4.3%) with the IL-6 -174 CC genotype, while it was present in 24.4% of GG/GC cases (p=0.06). By stepwise multivariate analysis (including RA duration, baseline DAS28, baseline HAQ, RF status, anti-CCP status and IL-6 genotype as covariates), the IL-6 -174CC genotype was selected as an independent predictor of no response to RTX by both EULAR and ACR≥50 criteria, while the IL-6R polymorphism resulted as not associated. No definite association between gene polymorphisms and IL-6 serum levels was noticed. Present results suggest a possible role for IL-6 genotyping to better plan treatment with RTX in RA, and larger studies are worthwhile.
鉴定生物制剂治疗类风湿关节炎（RA）应答的遗传生物标志物是一个重要问题。IL-6 是 B 细胞存活的关键细胞因子，本研究调查了接受利妥昔单抗（RTX）治疗的 158 例 RA 患者的白细胞介素 6（IL-6）-174G>C 和 IL-6 受体（IL-6R）D358A 基因多态性。128 例（81.0%）患者 RF 阳性，126 例（79.7%）患者抗 CCP 阳性。在第一次 RTX 输注后第 6 个月末，根据 EULAR 和 ACR 标准评估治疗应答。还研究了其与 IL-6 血清水平的可能关系。单因素分析显示，根据 EULAR 标准无应答者中 IL-6-174 CC 基因型患者（39.1%）比 GC/GG 患者（18.5%）更为常见（OR 2.83；95%CI=1.10-7.27；p=0.031）。只有 1 例（4.3%）IL-6-174 CC 基因型患者出现良好应答，而 GG/GC 病例中有 24.4%（p=0.06）出现良好应答。通过逐步多因素分析（包括 RA 病程、基线 DAS28、基线 HAQ、RF 状态、抗 CCP 状态和 IL-6 基因型作为协变量），IL-6-174CC 基因型被选为 EULAR 和 ACR≥50 标准下 RTX 无应答的独立预测因子，而 IL-6R 多态性则无相关性。未发现基因多态性与 IL-6 血清水平之间存在明确关联。目前的结果表明，对 IL-6 基因分型可能有助于更好地计划 RA 患者的 RTX 治疗，值得开展更大规模的研究。
