Objectives Increased circulating levels of CXCL13 reflect synovial production and indicate immune dysregulation in patients with rheumatoid arthritis (RA). Here we tested whether CXCL13 predicts response to first-line treatment with methotrexate (MTX) in patients with early RA, independently and in association with anti-citrullinated protein antibodies (ACPA) and IgM-rheumatoid factor (RF). Methods A prospective cohort of 243 early RA patients undergoing treat-to-target with MTX was evaluated. CXCL13, ACPA and IgM-RF were determined on baseline sera. Short-term variations of CXCL13 were measured after 2 months. The association of high CXCL13 (≥100 pg/ml) with disease remission after 6 months and escalation to second-line therapies within year 2 was evaluated in the total population and in ACPA-subgroups separately. Results High levels of CXCL13 were found in 53.6% of ACPA-positive and 31.5% of ACPA-negative patients, with minimal association with disease activity and RF. Serum CXCL13 remained stable after 2 months. High baseline CXCL13 independently predicted failure to achieve remission and more frequent requirement of second-line treatment in ACPA-positive patients, with adjusted ORs in the range of 0.17–0.49 for remission and 6.75 for second-line treatment. In ACPA-negative patients with high CXCL13, remission occurred at the expense of higher doses of MTX, and levels of CXCL13 predicted MTX escalations with an adjusted OR (95% CI) of 2.69 (1.35–5.34). Conclusions High serum levels of CXCL13 identify a subgroup of RA patients who are more refractory to first-line treatment with MTX. CXCL13 appears a promising biomarker of response to MTX in both ACPA-positive and -negative early RA.

中文翻译：

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高血清 CXCL13 水平预示着 ACPA 阳性和 ACPA 阴性早期类风湿关节炎对 csDMARD 的反应较低


目的 CXCL13 循环水平升高反映了滑膜的产生，并表明类风湿性关节炎 （RA） 患者的免疫失调。在这里，我们测试了 CXCL13 是否独立并联合抗瓜氨酸蛋白抗体 （ACPA） 和类风湿因子 （RF） 预测早期 RA 患者对甲氨蝶呤 （MTX） 一线治疗的反应。方法 对 243 例接受 MTX 靶向治疗的早期 RA 患者的前瞻性队列进行了评估。在基线血清上测定 CXCL13 、 ACPA 和 IgM-RF。2 个月后测量 CXCL13 的短期变化。在总人群和 ACPA 亚组中分别评估了高 CXCL13 （≥100 pg/ml） 与 6 个月后疾病缓解和 2 年内升级为二线治疗的相关性。结果 53.6% 的 ACPA 阳性患者和 31.5% 的 ACPA 阴性患者发现高水平的 CXCL13，与疾病活动和 RF 的相关性最小。血清 CXCL13 在 2 个月后保持稳定。高基线 CXCL13 独立预测 ACPA 阳性患者未能达到缓解和更频繁地需要二线治疗，调整后的 OR 在 0.17-0.49 的缓解和 6.75 的二线治疗范围内。在具有高 CXCL13 的 ACPA 阴性患者中，缓解是以更高剂量的 MTX 为代价的，CXCL13 水平预测 MTX 升高，调整后的 OR （95% CI） 为 2.69 （1.35-5.34）。结论 高血清 CXCL13 水平确定了对 MTX 一线治疗更难治的 RA 患者亚组。CXCL13 似乎是 ACPA 阳性和阴性早期 RA 中对 MTX 反应的有前途的生物标志物。