Mavragani Clio P, La Dan T, Stohl William, Crow Mary K
Hospital for Special Surgery, Weill Cornell Medical College, New York, NY, USA.
Arthritis Rheum. 2010 Feb;62(2):392-401. doi: 10.1002/art.27226.
Despite the substantial clinical efficacy of tumor necrosis factor alpha (TNFalpha) antagonist therapy in patients with rheumatoid arthritis (RA), some patients respond poorly to such agents. Since an interferon (IFN) signature is variably expressed among RA patients, we investigated whether plasma type I IFN activity might predict the response to TNF antagonist therapy.
RA patients (n = 35), the majority of whom were Hispanic, from a single center were evaluated before and after initiation of TNF antagonist therapy. As controls, 12 RA patients from the same center who were not treated with a TNF antagonist were studied. Plasma type I IFN activity was measured using a reporter cell assay, and disease status was assessed using the Disease Activity Score in 28 joints (DAS28). Levels of interleukin-1 receptor antagonist (IL-1Ra) were determined in baseline plasma samples using a commercial enzyme-linked immunosorbent assay. The clinical response was classified according to the European League Against Rheumatism criteria for improvement in RA.
Plasma type I IFN activity at baseline was significantly associated with clinical response (odds ratio 1.36 [95% confidence interval 1.05-1.76], P = 0.020), with high baseline IFN activity associated with a good response. Changes in DAS28 scores were greater among patients with a baseline plasma IFNbeta/alpha ratio >0.8 (indicating elevated plasma IFNbeta levels). Consistent with the capacity of IFNbeta to induce IL-1Ra, elevated baseline IL-1Ra levels were associated with better therapeutic outcomes (odds ratio 1.82 [95% confidence interval 1.1-3.29], P = 0.027).
The plasma type I IFN activity, the IFNbeta/alpha ratio, and the IL-1Ra level were predictive of the therapeutic response in TNF antagonist-treated RA patients, indicating that these parameters might define clinically meaningful subgroups of RA patients with distinct responses to therapeutic agents.
尽管肿瘤坏死因子α（TNFα）拮抗剂疗法在类风湿关节炎（RA）患者中具有显著的临床疗效，但一些患者对此类药物反应不佳。由于RA患者中干扰素（IFN）特征存在差异表达，我们研究了血浆I型干扰素活性是否可预测对TNF拮抗剂疗法的反应。
来自单一中心的35例RA患者（大多数为西班牙裔）在开始TNF拮抗剂治疗前后进行了评估。作为对照，研究了来自同一中心未接受TNF拮抗剂治疗的12例RA患者。使用报告细胞测定法测量血浆I型干扰素活性，并使用28个关节疾病活动评分（DAS28）评估疾病状态。使用商业酶联免疫吸附测定法测定基线血浆样本中白细胞介素-1受体拮抗剂（IL-1Ra）的水平。根据欧洲抗风湿病联盟关于RA改善的标准对临床反应进行分类。
基线时血浆I型干扰素活性与临床反应显著相关（比值比1.36 [95%置信区间1.05 - 1.76]，P = 0.020），基线干扰素活性高与良好反应相关。基线血浆IFNβ/α比值>0.8（表明血浆IFNβ水平升高）的患者中，DAS28评分变化更大。与IFNβ诱导IL-1Ra的能力一致，基线IL-1Ra水平升高与更好的治疗结果相关（比值比1.82 [95%置信区间1.1 - 3.29]，P = 0.027）。
血浆I型干扰素活性、IFNβ/α比值和IL-1Ra水平可预测TNF拮抗剂治疗的RA患者的治疗反应，表明这些参数可能定义对治疗药物有不同反应的RA患者具有临床意义的亚组。
