Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment
Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment
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DOI：
10.1016/j.jcf.2018.08.013
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发表时间：
2019-03-01
影响因子：
5.2
通讯作者：
Balogh, Istvan
中科院分区：
文献类型：
--
作者：
Nagy, Bela, Jr.;Bene, Zsolt;Balogh, Istvan
背景：我们最近发现人附睾蛋白 4 (HE4) 水平与囊性纤维化 (CF) 肺部疾病的严重程度相关。然而，尚无关于接受 CFTR 调节治疗的患者中 HE4 水平如何变化的数据。 方法：在这项回顾性临床研究中，纳入了 3 个独立的 CF 患者队列（美国：29 例、澳大利亚：12 例和爱尔兰：19 例），这些患者携带至少一种 III 类 CFTR CF 致病突变 (p.Gly551Asp)，并接受 CFTR 增强剂 ivacaftor 治疗。在治疗前（基线）和开始ivacaftor后1-6个月通过免疫测定法测量血浆HE4，并与FEV1（预测百分比）、汗液氯化物、C反应蛋白（CRP）和体重指数（BMI）相关。 结果：治疗1个月后，HE4水平显着低于基线，并持续降低至6个月。在合并组中回顾性观察到 HE4 和 FEV1 的绝对值和增量值之间存在显着负相关（r = -0.5376；P < .001 和 r = -0.3285；P < .001），包括通过多元回归分析得出 HE4 与 FEV1 的独立关联（β = -0.57，P = .019）。当 FEV1 平均变化 7%（0.722 [95% CI 0.581-0.863]；P = 0.029）用作分类器时，特别是在治疗的前 2 个月（0.806 [95% CI 0.665-0.947]；P < .001).结论：本研究表明 接受ivacaftor治疗的CF患者的血浆HE4水平与肺功能改善呈负相关。总体而言，这种潜在的生物标志物可能对 CFTR 调节治疗的常规临床和实验室随访有价值。 (C) 2018 年欧洲囊性纤维化协会。由 Elsevier B.V. 出版。保留所有权利。
Background: We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.Methods: In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1-6 months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI).Results: After 1 month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6 months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r = -0.5376; P < .001 and r = -0.3285; P< .001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (beta = -0.57, P = .019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581-0.863]; P = .029) were used as classifier, especially in the first 2 months of treatment (0.806 [95% CI 0.665-0.947]; P < .001).Conclusions: This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy. (C) 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.