血清 YKL-40 是肺泡蛋白沉积症的可靠生物标志物。

Serum YKL-40 is a reliable biomarker for pulmonary alveolar proteinosis.

机构信息

Interstitial and Rare Lung Disease Unit, Ruhrlandklinik, University of Duisburg-Essen, Essen, Germany.

Department of Respiratory Medicine, The First Affiliated Hospital of University of South China, Hunan, China.

出版信息

Respirology. 2017 Oct;22(7):1371-1378. doi: 10.1111/resp.13082. Epub 2017 May 31.

DOI:10.1111/resp.13082

PMID:28569052

Abstract

BACKGROUND AND OBJECTIVE

Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by alveolar filling. YKL-40, a chitinase-like protein produced by macrophages and epithelial cells, is increased in patients with interstitial lung diseases. We aimed to evaluate the role of YKL-40 as a biomarker for PAP.

METHODS

A total of 34 patients with autoimmune PAP and 50 healthy controls were studied. YKL-40 was measured by ELISA in serum and bronchoalveolar lavage fluid (BALF). Chitinase coding gene polymorphisms (CHI3L1-329 and -131) were detected by PCR and pyrosequencing. Correlations between serum YKL-40 levels and disease outcome were analysed.

RESULTS

Baseline serum and BALF levels of YKL-40 were higher in PAP patients than in controls (286 ± 27 ng/mL vs 42 ± 4 ng/mL, P < 0.0001; 323 ± 36 ng/mL vs 3 ± 1 ng/mL, P < 0.0001, respectively). Serum YKL-40 levels correlated with diffusing capacity of the lung for carbon monoxide (DL ) at baseline (P = 0.002) and over time (P < 0.0001). Patients with disease progression had higher baseline serum YKL-40 levels than those who remained stable or improved (P < 0.0001). A baseline cut-off level of 300 ng/mL was predictive of disease progression (HR (hazard ratio): 7.875, P = 0.001). The presence of the G allele was associated with higher serum and BALF levels of YKL-40.

CONCLUSION

YKL-40 is elevated in serum and BALF of PAP patients, and may be of clinical utility to predict outcome in PAP.

摘要

背景与目的

肺泡蛋白沉积症（PAP）是一种以肺泡填充为特征的罕见疾病。壳聚糖酶样蛋白 YKL-40 由巨噬细胞和上皮细胞产生，在间质性肺疾病患者中增加。我们旨在评估 YKL-40 作为 PAP 生物标志物的作用。

方法

共研究了 34 例自身免疫性 PAP 患者和 50 名健康对照者。通过酶联免疫吸附试验（ELISA）测量血清和支气管肺泡灌洗液（BALF）中的 YKL-40。通过 PCR 和焦磷酸测序检测壳聚糖编码基因多态性（CHI3L1-329 和 -131）。分析了血清 YKL-40 水平与疾病结局的相关性。

结果

与对照组相比，PAP 患者的基线血清和 BALF 中的 YKL-40 水平较高（286±27ng/mL 比 42±4ng/mL，P<0.0001；323±36ng/mL 比 3±1ng/mL，P<0.0001）。基线时，血清 YKL-40 水平与一氧化碳弥散量（DL ）相关（P=0.002），且随时间推移而变化（P<0.0001）。疾病进展的患者的基线血清 YKL-40 水平高于病情稳定或改善的患者（P<0.0001）。基线时 300ng/mL 的截止值可预测疾病进展（HR（风险比）：7.875，P=0.001）。G 等位基因的存在与血清和 BALF 中 YKL-40 水平升高相关。