Biomarkers of rheumatoid arthritis-associated interstitial lung disease.
Biomarkers of rheumatoid arthritis-associated interstitial lung disease.
复制标题
DOI：
10.1002/art.38904
复制
发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
Ascherman DP
中科院分区：
文献类型：
--
作者：
Chen J;Doyle TJ;Liu Y;Aggarwal R;Wang X;Shi Y;Ge SX;Huang H;Lin Q;Liu W;Cai Y;Koontz D;Fuhrman CR;Golzarri MF;Liu Y;Hatabu H;Nishino M;Araki T;Dellaripa PF;Oddis CV;Rosas IO;Ascherman DP
间质性肺病（ILD）是类风湿性关节炎（RA）的一种相对常见的关节外表现，可显著增加疾病负担和死亡率。本研究的目的是确定RA相关ILD的外周血标志物，这些标志物可以促进早期诊断，并提供有关这种潜在破坏性疾病并发症发病机制的见解。根据胸部高分辨率计算机断层扫描，入组特征明确的中国识别队列或美国复制队列的RA患者被细分为RA-无ILD、RA-轻度ILD或RA-晚期ILD。多重酶联免疫吸附试验（ELISA）和Luminex xMAP技术用于评估鉴定队列中的36种细胞因子/趋化因子、基质金属蛋白酶（MMP）和急性期蛋白。使用未校正和校正的逻辑回归模型来量化RA-ILD与目标生物标志物之间的关联强度。采用多重ELISA法对133例RA患者（50例RA-无ILD，41例RA-ILD，42例RA-不确定ILD）中的MMP-7和干扰素-γ-诱导蛋白10（IP-10）/CXCL 10进行鉴定，作为RA-ILD的潜在生物标志物。在中国识别队列以及美国RA和不同阶段ILD患者（22例RA-无ILD，49例RA-ILD，15例RA-不确定ILD）的独立队列中，通过标准固相夹心ELISA证实了这些结果，在未校正和校正的logistic回归分析中具有统计学显著性相关性。MMP-7和IP-10/CXCL 10的水平在患有ILD的RA患者的血清中升高，无论是轻度还是晚期，支持它们作为病理相关生物标志物的价值，可以有助于无创检测这种关节外疾病并发症。
Interstitial lung disease (ILD) is a relatively common extraarticular manifestation of rheumatoid arthritis (RA) that contributes significantly to disease burden and excess mortality. The purpose of this study was to identify peripheral blood markers of RA-associated ILD that can facilitate earlier diagnosis and provide insight regarding the pathogenesis of this potentially devastating disease complication. Patients with RA who were enrolled in a well-characterized Chinese identification cohort or a US replication cohort were subclassified as having RA–no ILD, RA–mild ILD, or RA–advanced ILD, based on high-resolution computed tomography scans of the chest. Multiplex enzyme-linked immunosorbent assays (ELISAs) and Luminex xMAP technology were used to assess 36 cytokines/chemokines, matrix metalloproteinases (MMPs), and acute-phase proteins in the identification cohort. Unadjusted and adjusted logistic regression models were used to quantify the strength of association between RA-ILD and biomarkers of interest. MMP-7 and interferon-γ–inducible protein 10 (IP-10)/CXCL10 were identified by multiplex ELISA as potential biomarkers for RA-ILD in 133 RA patients comprising the Chinese identification cohort (50 RA–no ILD, 41 RA-ILD, 42 RA–indeterminate ILD). The findings were confirmed by standard solid-phase sandwich ELISA in the Chinese identification cohort as well as an independent cohort of US patients with RA and different stages of ILD (22 RA–no ILD, 49 RA-ILD, 15 RA–indeterminate ILD), with statistically significant associations in both unadjusted and adjusted logistic regression analyses. Levels of MMP-7 and IP-10/CXCL10 are elevated in the serum of RA patients with ILD, whether mild or advanced, supporting their value as pathogenically relevant biomarkers that can contribute to noninvasive detection of this extraarticular disease complication.