Liang Liu, Chen Jiali, Di Chun, Zhan Minghua, Bao Huizhang, Xia Changsheng, Fan Chunhong, Liu Yudong
Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
Department of Clinical Laboratory, The Second People's Hospital of Qinzhou, Qinzhou, China.
Front Med (Lausanne). 2021 Oct 26;8:755268. doi: 10.3389/fmed.2021.755268. eCollection 2021.
Human epididymis protein 4 (HE4) have been implicated in the pulmonary involvements. We aimed to investigate the clinical utility of HE4 in clinical stratification in patients with rheumatoid arthritis (RA). This study included a discovery cohort comprising 70 RA patients and 64 healthy controls (HCs), and a validation cohort comprising 98 RA patients and 75 HCs. Human epididymis protein 4 were determined by electrochemical luminescence analyzer. The levels of HE4 were significantly elevated in patients with RA compared to HCs. The positive rates of HE4 in patients with RA and HCs were 50.0% and 0, respectively, in the discovery cohort and 53.1 and 1.3%, respectively, in the validation cohort. When RA patients were subgrouped according to HE4 status, HE4-positive group displayed higher prevalence of interstitial lung disease (ILD) compared to HE4-negative group (28.6 vs. 11.4% in discovery cohort and 57.7 vs. 8.7% in the validation cohort). A positive correlation between the levels of HE4 with the degree of lung impairment was identified. Receiver operating curve (ROC) analysis revealed an optimal cut-off value of 104.3 pmol/L in HE4 for distinguishing RA-ILD from RA-non ILD with the areas under the curve (AUC) of 0.790. Multivariate logistic regression analysis illustrated that high levels of HE4 independently identified patients with RA-ILD (OR, 9.080 < 0.001). Our findings showed a novel role of HE4 in RA risk stratification, suggest that introducing HE4 to the current RA test panel may serve as an indicator in identifying RA patients for further RA-ILD workups, such as high-resolution computed tomography (HRCT).
人附睾蛋白4（HE4）与肺部受累有关。我们旨在研究HE4在类风湿关节炎（RA）患者临床分层中的临床应用价值。本研究包括一个发现队列，由70例RA患者和64例健康对照（HCs）组成，以及一个验证队列，由98例RA患者和75例HCs组成。通过电化学发光分析仪测定人附睾蛋白4。与HCs相比，RA患者中HE4水平显著升高。在发现队列中，RA患者和HCs中HE4的阳性率分别为50.0%和0，在验证队列中分别为53.1%和1.3%。当根据HE4状态对RA患者进行亚组分析时，与HE4阴性组相比，HE4阳性组间质性肺疾病（ILD）的患病率更高（发现队列中为28.6%对11.4%，验证队列中为57.7%对8.7%）。确定HE4水平与肺损伤程度之间存在正相关。受试者工作特征曲线（ROC）分析显示，HE4区分RA-ILD与RA-非ILD的最佳截断值为104.3 pmol/L，曲线下面积（AUC）为0.790。多因素逻辑回归分析表明，高水平的HE4可独立识别RA-ILD患者（OR，9.080；P<0.001）。我们的研究结果显示了HE4在RA风险分层中的新作用，表明将HE4引入当前的RA检测组可能作为识别RA患者进行进一步RA-ILD检查（如高分辨率计算机断层扫描（HRCT））的指标。
