Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
Front Immunol. 2021 Jun 23;12:670642. doi: 10.3389/fimmu.2021.670642. eCollection 2021.
We aimed to investigate the clinical utility of human epididymis protein 4, a tumor biomarker being widely utilized in clinical practice in the diagnosis of ovarian cancer, in primary Sjögren's Syndrome (pSS).
A total of 109 pSS patients and 113 healthy controls (HCs) were included in the study. HE4 were determined by Roche Cobas E601 electrochemical luminescence analyzer. Clinical and laboratory findings were reviewed, and the relationships between HE4 and clinical parameters were determined by Spearman's correlation test. The European league against rheumatism Sjögren's syndrome disease activity index (ESSDAI) was utilized to evaluate disease activity.
The levels of HE4 were significantly elevated in patients with pSS compared to HCs (103.65 pmol/L 46.52 pmol/L, <0.001). The levels of HE4 were positively correlated with ESSDAI scores (=0.462, <0.001). Significant positive correlations between the levels of HE4 with pulmonary involvements (=0.442, <0.001) and renal involvements (=0.320, =0.001) were observed. Receiver operating curve (ROC) analysis revealed an optimal cut-off value of 104.90 pmol/L and 128.05 pmol/L for distinguishing patients with pulmonary and renal involvements, with the areas under the ROC curve (AUCs) of 0.778 (95%CI 0.685-0.870, <0.001) and 0.768 (95%CI 0.646-0.891, =0.001), respectively. Among patients with pulmonary involvement, the levels of HE4 were positively correlated with the semiquantitative HRCT grade (=0.417, =0.016), and negatively correlated with the percentage of forced vital capacity (FVC) (= -0.460, =0.047) and diffusing capacity of the lung for carbon monoxide (DLco) (= -0.623, =0.004). For patients with renal involvement, HE4 was positively correlated with creatinine (=0.588, =0.021) and negatively correlated with estimated glomerular filtration rate (= -0.599, =0.030).
Our findings demonstrated a novel role of HE4 in clinical stratification of pSS, suggesting that introducing HE4 to the current pSS test panel may provide additional diagnostic value, particularly in evaluating disease activity and pulmonary/renal involvements.
我们旨在探讨人附睾蛋白 4（一种在卵巢癌诊断中广泛应用于临床的肿瘤标志物）在原发性干燥综合征（pSS）中的临床应用价值。
本研究纳入了 109 例 pSS 患者和 113 例健康对照者（HCs）。HE4 采用罗氏 Cobas E601 电化学发光分析仪进行测定。回顾临床和实验室检查结果，并采用 Spearman 相关检验确定 HE4 与临床参数之间的关系。采用欧洲抗风湿病联盟干燥综合征疾病活动指数（ESSDAI）评估疾病活动度。
pSS 患者的 HE4 水平明显高于 HCs（103.65 pmol/L vs. 46.52 pmol/L，<0.001）。HE4 水平与 ESSDAI 评分呈正相关（r=0.462，<0.001）。HE4 水平与肺部受累（r=0.442，<0.001）和肾脏受累（r=0.320，=0.001）呈显著正相关。受试者工作特征曲线（ROC）分析显示，区分有肺部和肾脏受累的患者的最佳截断值分别为 104.90 pmol/L 和 128.05 pmol/L，ROC 曲线下面积（AUC）分别为 0.778（95%CI 0.685-0.870，<0.001）和 0.768（95%CI 0.646-0.891，=0.001）。在有肺部受累的患者中，HE4 水平与半定量高分辨率 CT（HRCT）评分呈正相关（r=0.417，=0.016），与用力肺活量（FVC）的百分比（r=-0.460，=0.047）和一氧化碳弥散量（DLco）（r=-0.623，=0.004）呈负相关。对于有肾脏受累的患者，HE4 与肌酐（r=0.588，=0.021）呈正相关，与估算肾小球滤过率（r=-0.599，=0.030）呈负相关。
我们的研究结果表明 HE4 在 pSS 的临床分层中有新的作用，提示将 HE4 引入当前的 pSS 检测方案可能提供额外的诊断价值，尤其是在评估疾病活动度和肺部/肾脏受累方面。
