血清YKL-40在诊断抗黑色素瘤分化相关基因5阳性皮肌炎合并严重肺损伤中的价值

目的:研究血清及支气管肺泡灌洗液(bronchoalveolar lavage fluid, BALF)中YKL-40(chitinase-3-like-1 protein)在抗黑色素瘤分化相关基因5(anti-melanoma differentiation-associated gene 5, MDA5)阳性皮肌炎(dermatomyositis, DM)合并严重肺损伤中的价值,严重肺损伤包括快速进展间质性肺病(rapidly progressive interstitial lung disease, RP-ILD)和肺部感染。方法:选择2013—2018年中日友好医院风湿免疫科住院的抗MDA5阳性DM患者的病例资料进行回顾性分析,收集患者的人口学信息,临床、实验室及影像学检查资料,应用酶联免疫吸附法检测患者血清和BALF中YKL-40水平。绘制受试者工作特征(receiver operating characteristic, ROC)曲线,计算曲线下面积(area under the curve, AUC),评估血清YKL-40对肺损伤的诊断效能。间质性肺病(interstitial lung disease, ILD)由胸部高分辨率CT(high-resolution CT, HRCT)证实。RP-ILD定义为呼吸道症状在3个月内进行性加重,出现呼吸困难和低氧血症,或胸部HRCT显示ILD较之前加重或出现新的ILD。肺部感染经痰、血液、BALF、肺穿刺活检样本检验出病原体确诊。结果:共收集到168例抗MDA5阳性DM患者病例,其中154例合并ILD,66例(39.3%)表现为RP-ILD。经病原学依据证实合并肺部感染患者70例。合并RP-ILD患者中39例(59.1%)合并肺部感染,而非RP-ILD患者仅31例(30.4%)合并肺部感染。RP-ILD合并肺部感染的发生率高于非RP-ILD合并肺部感染者(P<0.001)。血清YKL-40水平在RP-ILD合并肺部感染组高于RP-ILD未合并肺部感染组、非RP-ILD合并肺部感染组和非RP-ILD未合并肺部感染组83(42~142) vs. 42(21~91) vs. 43(24~79) vs. 38(22~69), P<0.01]。血清YKL-40诊断抗MDA5阳性DM患者RP-ILD合并肺部感染的敏感性、特异性及AUC分别为75%、67%、0.72,其诊断同时存在RP-ILD和肺部感染的抗MDA5阳性DM患者的AUC较诊断仅有RP-ILD和仅有肺部感染者的AUC高,且差异有统计学意义(0.72 vs. 0.54和0.55, Z=2.10和2.11, P<0.05)。结论:抗MDA5阳性DM患者合并RP-ILD和肺部感染预后差,血清YKL-40水平对这类患者同时合并RP-ILD和肺部感染有一定的诊断价值。

Value of serum YKL-40 in the diagnosis of anti-MDA5-positive patients with derma-tomyositis complicated with severe pulmonary injury

Objective: To investigate the value of serum and bronchoalveolar lavage fluid (BALF) chitinase-3-like-1 protein (YKL-40) in the diagnosis of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM) patients complicated with serious pulmonary injury, including rapidly progressive interstitial lung disease (RP-ILD) and pulmonary infection. Methods: Anti-MDA5 antibodies positive patients with DM who were hospitalized in the Department of Rheumatology of China-Japan Friendship Hospital from 2013 to 2018 were involved in this study. Demographic information, clinical, laboratory and imaging data were retrospectively collected. ELISA was used to detect the serum and BALF levels of YKL-40. The receiver operating characteristic (ROC) curve was drawn,and the area under ROC curve (AUC) was used to evaluate the diagnostic value of serum YKL-40 for pulmonary injury.Interstitial lung disease (ILD) was confirmed by chest high-resolution CT (HRCT). RP-ILD was defined as progressive respiratory symptoms such as dyspnea and hypoxemia within 3 months, and/or deterioration of interstitial changes or appearace of new pulmonary interstitial lesions on chest HRCT. Pulmonary infection was considered as positive pathogens detected in qualified sputum, blood, bronchoalveolar lavage fluid or lung biopsy specimens. Results: A total of 168 anti-MDA5-positive DM patients including 108 females and 60 males were enrolled in the study. Of these patients, 154 had ILD, and 66(39.3%) of them presented RP-ILD. Seventy patients with pulmonary infection were confirmed by etiology. In the patients with RP-ILD, 39 (59.1%) of them were complicated with pulmonary infection. While only 31 cases(30.4%) had pulmonary infection in the non-RP-ILD patients. The incidence of pulmonary infection in the patients with RP-ILD was significantly higher than that of those with non-RP-ILD (P<0.001). The serum YKL-40 levels in the RP-ILD patients with pulmonary infection were the highest compared with RP-ILD without pulmonary infection, non-RP-ILD with pulmonary infection and non-RP-ILD without pulmonary infection groups among all the patients 83 (42-142) vs. 42 (21-91) vs. 43 (24-79) vs. 38 (22-69), P<0.01].The sensitivity, specificity and AUC of serum YKL-40 in the diagnosis of RP-ILD complicated with pulmonary infection were 75%, 67%, and 0.72, respectively. The AUC of diagnosed of anti-MDA5 positive DM patients complicated with RP-ILD and pulmonary infection was higher than that of patients complicated with only RP-ILD and only pulmonary infection (0.72 vs. 0.54 and 0.55, Z=2.10 and 2.11, P<0.05). Conclusion: The prognosis of anti-MDA5-positive DM patients with RP-ILD and pulmonary infection were poor. Serum YKL-40 level can be used as a helpful tool for the diagnosis of coexistence of these conditions in the patients.