Zhao Juan, Ye Xia, Zhang Zhuoli
Department of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing, 100034, People's Republic of China.
Clin Rheumatol. 2020 Sep;39(9):2573-2581. doi: 10.1007/s10067-020-05043-1. Epub 2020 Mar 23.
Tumor necrosis factor-α (TNFα) inhibitors (TNFi) have greatly improved the prognosis of RA and become the first therapeutic option for patients who failed the conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) therapy, but not all these patients respond well to TNFi. So far, there has been no definite biomarker to predict the response to TNFi yet.
Sixty rheumatoid arthritis (RA) patients with disease duration more than 6 months and at least low disease activity defined by DAS28-CRP > 3.2 although after csDMARDs (including MTX and/or leflunomide) treatment for more than 3 months were included. They were further treated with TNFα receptor Fc fusion protein and MTX 10 mg per week for 12 weeks. Soluble ICAM-1 (sICAM-1) and CXCL13 concentrations in sera from 60 RA patients and 20 healthy controls were tested by ELISA right before and at the end of 12 weeks of TNFi therapy. The correlation between sICAM-1 and CXCL13 with disease activity and their predictive values for TNFi response were analyzed.
The mean age of the 60 patients was 54.8 ± 11.6 years. Serum sICAM-1 and CXCL13 concentrations were higher in RA patients than heathy controls, higher in seropositive RA patients than in seronegative ones, and higher in RA patients with higher disease activity. Serum sICAM-1 and CXCL13 levels were decreased after TNFi therapy, especially in good responders. Baseline sICAM-1 concentration was independently associated with the EULAR response (p = 0.033, OR = 1.014, 95% CI = 1.003-1.026). The sICAM-1/CXCL13 patients had the highest response rate, which was significantly higher than the sICAM-1/CXCL13 group (OR = 8.143, 95% CI = 1.040-75.482, p = 0.045).
sICAM-1 and CXCL13 are elevated in RA patients and correlated with disease activity. sICAM-1 is an independent predictor of TNFi response in csDMARDs refractory RA patients. Key Points • This study confirmed the predictive value of soluble ICAM-1 (sICAM-1) and CXCL13 on the response to TNFi in RA patient. • Baseline sICAM-1 concentration was independently associated with the EULAR response. • The sICAM-1/CXCL13 patients had significantly higher response rate than the sICAM-1/CXCL13 group.
肿瘤坏死因子-α（TNFα）抑制剂（TNFi）极大地改善了类风湿关节炎（RA）的预后，成为传统合成改善病情抗风湿药（csDMARDs）治疗失败患者的首选治疗方案，但并非所有这些患者对TNFi反应良好。迄今为止，尚无明确的生物标志物可预测对TNFi的反应。
纳入60例病程超过6个月且尽管接受csDMARDs（包括甲氨蝶呤和/或来氟米特）治疗超过3个月但疾病活动度至少为低疾病活动度（由DAS28-CRP>3.2定义）的类风湿关节炎（RA）患者。他们进一步接受TNFα受体Fc融合蛋白和每周10mg甲氨蝶呤治疗12周。在TNFi治疗前及治疗12周结束时，通过酶联免疫吸附测定（ELISA）检测60例RA患者和20例健康对照血清中可溶性细胞间黏附分子-1（sICAM-1）和CXC趋化因子配体13（CXCL13）的浓度。分析sICAM-1和CXCL13与疾病活动度的相关性及其对TNFi反应的预测价值。
60例患者的平均年龄为54.8±11.6岁。RA患者血清sICAM-1和CXCL13浓度高于健康对照，血清阳性RA患者高于血清阴性患者，疾病活动度较高的RA患者高于疾病活动度较低者。TNFi治疗后血清sICAM-1和CXCL13水平降低，尤其是反应良好者。基线sICAM-1浓度与欧洲抗风湿病联盟（EULAR）反应独立相关（p=0.033，OR=1.014，95%CI=1.003-1.026）。sICAM-1/CXCL13患者的反应率最高，显著高于sICAM-1/CXCL13组（OR=8.143，95%CI=1.040-75.482，p=0.045）。
RA患者中sICAM-1和CXCL13升高且与疾病活动度相关。sICAM-1是csDMARDs难治性RA患者对TNFi反应的独立预测指标。要点 • 本研究证实了可溶性细胞间黏附分子-1（sICAM-1）和CXC趋化因子配体13（CXCL13）对RA患者TNFi反应的预测价值。 • 基线sICAM-1浓度与EULAR反应独立相关。 • sICAM-1/CXCL13患者的反应率显著高于sICAM-1/CXCL13组。
