可溶性程序性死亡分子 1（sPD-1）作为类风湿关节炎间质性肺病的预测因子。
Soluble programmed death molecule 1 (sPD-1) as a predictor of interstitial lung disease in rheumatoid arthritis.
机构信息
Department of Rheumatology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China.
Department of Medical, Jiaxing University Affiliated Women and Children Hospital (Jiaxing Maternity and Child Health Care Hospital), Jiaxing, 314000, China.
出版信息
BMC Immunol. 2021 Oct 15;22(1):69. doi: 10.1186/s12865-021-00460-6.
BACKGROUND
Previous studies have indicated that the programmed death molecule 1 (PD-1) signaling pathway may play a key role in rheumatoid arthritis (RA). However, the pathogenesis of rheumatoid arthritis-related interstitial lung disease (RA-ILD) is not clear. We examined the serum levels of soluble PD-1 in patients with RA and its relationship with RA-ILD.
METHODS
Blood samples were obtained from 87 patients with RA (58 with ILD and 29 without ILD) and 45 healthy controls. Serum sPD-1 was measured by Enzyme-Linked Immunosorbent Assay. The pulmonary interstitial disease score was completed by a pulmonary physician and a radiologist through chest high-resolution computed tomography. Patients with RA-ILD were tested for lung function [e.g., forced vital capacity (FVC%), diffusing capacity of lungs for carbon monoxide (DLCO%)]. Associations between ILD and various markers, including sPD-1 and confounding factors, were investigated by logistic regression analysis. Diagnostic values of sPD-1 for the presence of ILD were investigated using receiver operating characteristic curve analysis.
RESULTS
Serum sPD-1 levels were higher in RA patients with ILD than in RA patients without ILD and healthy controls (185.1 ± 109.0 pg/ml vs. 119.1 ± 77.5 pg/ml vs. 52.1 ± 21.7 pg/ml, P < 0.05). Serum sPD-1 levels were positively correlated with RF titer (P = 0.02, r = 0.249), anti-cyclic citrullinated peptide antibody status (P = 0.02, r = 0.243), and serum IgG levels (P < 0.001, r = 0.368), negatively associated with FVC% (P = 0.02, r = - 0.344), forced expiratory volume (FEV1%) (P = 0.01, r = - 0.354), total lung capacity (TLC%) (P = 0.046, r = - 0.302), and was independently associated with the presence of ILD in RA patients by multivariate logistic regression analysis. The sensitivity and specificity of sPD-1 levels for the detection of ILD in RA patients were 58.6% and 75.9%, respectively. The area under the curve was 0.689.
CONCLUSION
Serum sPD-1 levels were increased in RA patients with ILD. Increased sPD-1 may be a valuable biomarker to predict the presence of ILD in patients with RA.
背景
先前的研究表明，程序性死亡分子 1（PD-1）信号通路可能在类风湿关节炎（RA）中发挥关键作用。然而，类风湿关节炎相关间质性肺病（RA-ILD）的发病机制尚不清楚。我们检测了 RA 患者血清中可溶性 PD-1 的水平及其与 RA-ILD 的关系。
方法
采集 87 例 RA 患者（58 例伴ILD，29 例不伴ILD）和 45 例健康对照者的血样。采用酶联免疫吸附试验检测血清 sPD-1。由肺科医生和放射科医生通过胸部高分辨率计算机断层扫描完成肺间质疾病评分。对 RA-ILD 患者进行肺功能检查[如用力肺活量（FVC%）、一氧化碳弥散量（DLCO%）]。采用逻辑回归分析探讨ILD与 sPD-1 等标志物及混杂因素之间的关系。采用受试者工作特征曲线分析评估 sPD-1 对 ILD 存在的诊断价值。
结果
RA 伴 ILD 患者血清 sPD-1 水平高于 RA 不伴 ILD 患者和健康对照者（185.1±109.0 pg/ml 比 119.1±77.5 pg/ml 比 52.1±21.7 pg/ml，P＜0.05）。血清 sPD-1 水平与 RF 滴度（P=0.02，r=0.249）、抗环瓜氨酸肽抗体状态（P=0.02，r=0.243）和血清 IgG 水平（P＜0.001，r=0.368）呈正相关，与 FVC%（P=0.02，r=-0.344）、用力呼气量（FEV1%）（P=0.01，r=-0.354）、肺总量（TLC%）（P=0.046，r=-0.302）呈负相关。多元逻辑回归分析显示，血清 sPD-1 水平是 RA 患者 ILD 的独立相关因素。sPD-1 水平对 RA 患者 ILD 的检出率为 58.6%，特异性为 75.9%，ROC 曲线下面积为 0.689。
结论
RA 伴 ILD 患者血清 sPD-1 水平升高。升高的 sPD-1 可能是预测 RA 患者 ILD 存在的有价值的生物标志物。
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