METHODS: A total of 55 CTD-ILD patients with UIP pattern (UIP-CTD) and 52 healthy controls were enrolled in this study. The serum levels of HE4 and Krebs von den Lungen-6 (KL-6) were evaluated in both cohorts. In addition, immunohistochemistry analysis for HE4 was performed on the lung sections of 6 patients with rheumatoid arthritis-associated UIP (UIP-RA) and 6 patients with early-stage lung cancer as normal control.
RESULTS: The levels of serum HE4 and KL-6 were higher in patients with UIP-CTD than in healthy controls (292.3 pmol/L versus 79.5 pmol/L for HE4, p < 0.001; 1091.0 IU/mL versus 171.5 IU/mL for KL-6, p < 0.001). Significant correlations between serum HE4 levels and percentpredicted forced vital capacity (FVC%) (r = -0.425, p = 0.004), percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) (r = -0.447, p = 0.003), and Gender-Age-Physiology (GAP) index (r = 0.494, p < 0.001) were observed in UIP-CTD patients. In immunohistochemistry analysis, elevated expression of HE4 in bronchiolar epithelium and mesenchyme was observed in patients with UIP-RA compared with controls. The serum levels of HE4 (≥277.5 pmol/L) and GAP index were related to an increased risk of mortality (HR = 3.884, p = 0.034; HR = 1.480, p = 0.028, respectively).
CONCLUSIONS: The expression of HE4 in serum and lung specimens was significantly elevated in UIP-CTD patients. Moreover, serum HE4 may be utilized as a biomarker to evaluate the severity of disease and predict the prognosis of UIP-CTD patients.
方法:本研究共纳入55例CTD-ILD患者(UIP-CTD)和52例健康对照。在两个队列中评估了HE4和KrebsvondenLungen-6(KL-6)的血清水平。此外,对6例类风湿性关节炎相关UIP(UIP-RA)患者和6例早期肺癌患者的肺切片进行了HE4的免疫组织化学分析作为正常对照。
结果:UIP-CTD患者的血清HE4和KL-6水平高于健康对照组(HE4为292.3pmol/L对79.5pmol/L,p<0.001;KL-6为1091.0IU/mL对171.5IU/mL,p<0.001)。血清HE4水平与预测的强迫肺活量百分比(FVC%)之间存在显着相关性(r=-0.425,p=0.004),肺一氧化碳的预测扩散能力百分比(DLCO%)(r=-0.447,p=0.003),在UIP-CTD患者中观察到性别-年龄-生理学(GAP)指数(r=0.494,p<0.001)。在免疫组织化学分析中,与对照组相比,UIP-RA患者的细支气管上皮和间充质中HE4的表达升高。血清HE4水平(≥277.5pmol/L)和GAP指数与死亡风险增加相关(HR=3.884,p=0.034;HR=1.480,p=0.028)。
结论:UIP-CTD患者血清和肺标本中HE4的表达明显升高。此外,血清HE4可作为评价UIP-CTD患者疾病严重程度和预测预后的生物标志物。