Zhang Mingxia, Zhang Liyun, E Linning, Xu Ke, Wang Xu Fei, Zhang Bin, Su Jie, Meng Zemin
Department of Laboratory medicine, Shanxi Bethune Hospital, Shanxi Province, P.R. China.
Department of Rheumatology and Immunology, Shanxi Bethune Hospital, Shanxi Province, China.
Ther Adv Chronic Dis. 2020 Sep 12;11:2040622320956420. doi: 10.1177/2040622320956420. eCollection 2020.
Human epididymis protein 4 (HE4, also known as WFDC-2) has been implicated in fibrotic disorders pathobiology. We tested the hypothesis that HE4 may be used as a candidate biomarker for systemic sclerosis (SSc)-related interstitial lung disease (SSc-ILD).
A total of 169 consecutive SSc patients and 169 age-and sex-matched healthy controls were enrolled and blood samples were collected. Pulmonary function tests (PFTs) and paired lavage was performed on 169 patients and 37 healthy controls. All patients were classified as having SSc-no ILD or SSc-ILD, based on high-resolution computed tomography (CT) scans of the chest, and a semiquantitative grade of ILD extent was evaluated through CT scans (grade 1, 0-25%; grade 2, 26-50%; grade 3, 51-75%; grade 4, 76-100%). Serum and bronchoalveolar lavage fluid (BALF) HE4 levels were measured by enzyme-linked immunosorbent assay.
Serum HE4 levels were higher in SSc patients [median (interquartile range), 139.4 (85.9-181.8) pmol/l] compared with healthy controls [39.5 (24.3-54.2) pmol/l, < 0.001] and were higher in patients with SSc-ILD [172.1 (94.8-263.3) pmol/l] than in those with SSc-no ILD [97.4 (85.5-156.5) pmol/l, < 0.001]. This observation was replicated in the BALF samples. Corresponding values were 510.8 (144.6-1013.8) pmol/l for SSc cohort, 754.4 (299-1060) pmol/l for SSc-ILD, 555.1 (203.7-776.2) pmol/l for SSc-no ILD, and 238.7 (97.7-397.6) pmol/l for controls. The semiquantitative grade of ILD on CT scan was significantly proportional to the HE4 levels and the lung function parameter (i.e., FVC) had a negative correlation with the HE4 levels.
This is the first study to demonstrate the potential clinical utility of blood and BALF HE4 as a biomarker for SSc-ILD. Future prospective validation studies are warranted.
人附睾蛋白4（HE4，也称为WFDC - 2）已被证明与纤维化疾病的病理生物学有关。我们检验了HE4可能作为系统性硬化症（SSc）相关间质性肺病（SSc - ILD）候选生物标志物的假设。
共纳入169例连续的SSc患者和169例年龄及性别匹配的健康对照，并采集血样。对169例患者和37例健康对照进行了肺功能测试（PFTs）和配对灌洗。所有患者根据胸部高分辨率计算机断层扫描（CT）分为SSc无ILD或SSc - ILD，并通过CT扫描评估ILD程度的半定量分级（1级，0 - 25%；2级，26 - 50%；3级，51 - 75%；4级，76 - 100%）。采用酶联免疫吸附测定法测量血清和支气管肺泡灌洗液（BALF）中的HE4水平。
与健康对照[39.5（24.3 - 54.2）pmol/l，<0.001]相比，SSc患者血清HE4水平更高[中位数（四分位间距），139.4（85.9 - 181.8）pmol/l]，且SSc - ILD患者[172.1（94.8 - 263.3）pmol/l]高于SSc无ILD患者[97.4（85.5 - 156.5）pmol/l，<0.001]。这一观察结果在BALF样本中得到了重复。SSc队列相应值为510.8（144.6 - 1013.8）pmol/l，SSc - ILD为754.4（299 - 1060）pmol/l，SSc无ILD为555.1（203.7 - 776.2）pmol/l，对照为238.7（97.7 - 397.6）pmol/l。CT扫描上ILD的半定量分级与HE4水平显著相关，肺功能参数（即FVC）与HE4水平呈负相关。
这是第一项证明血液和BALF中HE4作为SSc - ILD生物标志物潜在临床应用价值的研究。未来有必要进行前瞻性验证研究。
