Biologic predictors of clinical improvement in rituximab-treated refractory myositis.
Biologic predictors of clinical improvement in rituximab-treated refractory myositis.
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DOI：
10.1186/s12891-015-0710-3
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发表时间：
2015-09-17
影响因子：
2.3
通讯作者：
RIM Study Group
中科院分区：
文献类型：
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作者：
Reed AM;Crowson CS;Hein M;de Padilla CL;Olazagasti JM;Aggarwal R;Ascherman DP;Levesque MC;Oddis CV;RIM Study Group
研究生物标志物特征与肌炎自身抗体（autoAb）联合作为利妥昔单抗治疗的难治性肌炎患者疾病改善的预测因子的纵向效用。在RIM试验中，所有受试者均连续2周接受利妥昔单抗治疗。使用治疗开始作为基线，在基线和利妥昔单抗后用多重夹心免疫测定法分析血清样品（n = 177），以定量1型IFN调节的和其他促炎趋化因子和细胞因子。生成以下途径的生物标志物评分：1型IFN诱导型（IFNCK）、先天性、Th 1、Th 2、Th 17和调节性细胞因子。基线时通过免疫沉淀法测定的肌炎自身抗体（抗合成酶n = 28，TIF-γ n = 19，Mi-2 n = 25，SRP n = 21，MJ n = 18，非MAA n = 24，未鉴定自身抗体n = 9，无自身抗体n = 33）与结局指标相关。Kruskal-Wallis秩和检验用于比较。肌肉疾病和医生总体疾病活动VAS评分（0-100 mm）的平均（SD）值分别为46（22）和49（19）。与其他autoAb组相比，抗合成酶（43）、TIF 1-γ（31）和Mi-2（30）受试者的基线IFNCK评分（中位数）较高（p < 0.001）。在利妥昔单抗治疗后16周，抗合成酶和Mi-2 autoAb阳性受试者和非MAA受试者的IFNCK评分改善更大（-6.7，-6.1和-7.2，p < .001）。IFNCK高评分（>30）和自身抗体组（Mi-2、非MAA和未定义的自身抗体）均显示出基于肌肉VAS的最大临床改善（肌肉相互作用p = 0.075）。生物标志物特征与自身抗体结合有助于预测难治性肌炎对利妥昔单抗的反应。生物标志物和临床反应在利妥昔单抗后16周最大。
To examine the longitudinal utility of a biomarker signature in conjunction with myositis autoantibodies (autoAbs) as predictors of disease improvement in refractory myositis patients treated with rituximab. In the RIM Trial, all subjects received rituximab on 2 consecutive weeks. Using start of treatment as baseline, serum samples (n = 177) were analyzed at baseline and after rituximab with multiplexed sandwich immunoassays to quantify type-1 IFN-regulated and other pro-inflammatory chemokines and cytokines. Biomarker scores were generated for the following pathways: type-1 IFN-inducible (IFNCK), innate, Th1, Th2, Th17 and regulatory cytokines. Myositis autoAbs (anti-synthetase n = 28, TIF-γ n = 19, Mi-2 n = 25, SRP n = 21, MJ n = 18, non-MAA n = 24, unidentified autoantibody n = 9, and no autoantibodies n = 33) determined by immunoprecipitation at baseline, were correlated with outcome measures. Kruskal-Wallis rank sum tests were used for comparisons. The mean (SD) values for muscle disease and physician global disease activity VAS scores (0–100 mm) were 46 (22) and 49 (19). IFNCK scores (median values) were higher at baseline in subjects with anti-synthetase (43), TIF1-γ (31) and Mi-2 (30) compared with other autoAb groups (p < 0.001). At 16 weeks after rituximab, anti-synthetase and Mi-2 autoAb positive subjects and non-MAA had a greater improvement in IFNCK scores (− 6.7, − 6.1 and −7.2, p < .001). Both IFNCK high scores (>30) and autoAb group (Mi-2, non-MAA, and undefined autoantibody) demonstrated the greatest clinical improvement based on muscle VAS (muscle-interaction p = 0.075). Biomarker signatures in conjunction with autoAbs help predict response to rituximab in refractory myositis. Biomarker and clinical responses are greatest at 16 weeks after rituximab.