血清生物标志物可提高类风湿关节炎-间质性肺疾病的检测率。

Detection of Rheumatoid Arthritis-Interstitial Lung Disease Is Enhanced by Serum Biomarkers.

作者信息

Doyle Tracy J, Patel Avignat S, Hatabu Hiroto, Nishino Mizuki, Wu Guodong, Osorio Juan C, Golzarri Maria F, Traslosheros Andres, Chu Sarah G, Frits Michelle L, Iannaccone Christine K, Koontz Diane, Fuhrman Carl, Weinblatt Michael E, El-Chemaly Souheil Y, Washko George R, Hunninghake Gary M, Choi Augustine M K, Dellaripa Paul F, Oddis Chester V, Shadick Nancy A, Ascherman Dana P, Rosas Ivan O

机构信息

1 Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

2 Center for Pulmonary Functional Imaging.

出版信息

Am J Respir Crit Care Med. 2015 Jun 15;191(12):1403-12. doi: 10.1164/rccm.201411-1950OC.

DOI:10.1164/rccm.201411-1950OC

PMID:25822095

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4476561/

Abstract

RATIONALE

Interstitial lung disease (ILD), a leading cause of morbidity and mortality in rheumatoid arthritis (RA), is highly prevalent, yet RA-ILD is underrecognized.

OBJECTIVES

To identify clinical risk factors, autoantibodies, and biomarkers associated with the presence of RA-ILD.

METHODS

Subjects enrolled in Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) and American College of Rheumatology (ACR) cohorts were evaluated for ILD. Regression models were used to assess the association between variables of interest and RA-ILD. Receiver operating characteristic curves were generated in BRASS to determine if a combination of clinical risk factors and autoantibodies can identify RA-ILD and if the addition of investigational biomarkers is informative. This combinatorial signature was subsequently tested in ACR.

MEASUREMENTS AND MAIN RESULTS

A total of 113 BRASS subjects with clinically indicated chest computed tomography scans (41% with a spectrum of clinically evident and subclinical RA-ILD) and 76 ACR subjects with research or clinical scans (51% with a spectrum of RA-ILD) were selected. A combination of age, sex, smoking, rheumatoid factor, and anticyclic citrullinated peptide antibodies was strongly associated with RA-ILD (areas under the curve, 0.88 for BRASS and 0.89 for ACR). Importantly, a combinatorial signature including matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly increased the areas under the curve to 0.97 (P = 0.002, BRASS) and 1.00 (P = 0.016, ACR). Similar trends were seen for both clinically evident and subclinical RA-ILD.

CONCLUSIONS

Clinical risk factors and autoantibodies are strongly associated with the presence of clinically evident and subclinical RA-ILD on computed tomography scan in two independent RA cohorts. A biomarker signature composed of matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly strengthens this association. These findings may facilitate identification of RA-ILD at an earlier stage, potentially leading to decreased morbidity and mortality.

摘要

理论依据

间质性肺病（ILD）是类风湿关节炎（RA）发病和死亡的主要原因，其发病率很高，但RA-ILD却未得到充分认识。

目的

确定与RA-ILD存在相关的临床危险因素、自身抗体和生物标志物。

方法

对参与布莱根妇女医院类风湿关节炎序贯研究（BRASS）和美国风湿病学会（ACR）队列的受试者进行ILD评估。采用回归模型评估感兴趣变量与RA-ILD之间的关联。在BRASS中生成受试者工作特征曲线，以确定临床危险因素和自身抗体的组合是否能够识别RA-ILD，以及添加研究性生物标志物是否具有参考价值。随后在ACR中对这种组合特征进行测试。

测量指标及主要结果

共选取了113例接受临床胸部计算机断层扫描的BRASS受试者（41%患有一系列临床明显和亚临床RA-ILD）以及76例接受研究或临床扫描的ACR受试者（51%患有一系列RA-ILD）。年龄、性别、吸烟、类风湿因子和抗环瓜氨酸肽抗体的组合与RA-ILD密切相关（曲线下面积，BRASS为0.88，ACR为0.89）。重要的是，包括基质金属蛋白酶7、肺及激活调节趋化因子和表面活性蛋白D的组合特征显著提高了曲线下面积，分别达到0.97（P = 0.002，BRASS）和1.00（P = 0.016，ACR）。临床明显和亚临床RA-ILD均呈现类似趋势。