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半乳凝素在慢性肺移植功能障碍中的作用。

The Role of Galectins in Chronic Lung Allograft Dysfunction.

机构信息

Respiratory Diseases Unit, Department of Medical Sciences, University Hospital of Siena (Azienda Ospedaliera Universitaria Senese, AOUS), Viale Bracci, 53100, Siena, Italy.

Thoracic Surgery Unit, Cardio-Thoracic and Vascular Department, University Hospital of Siena (Azienda Ospedaliera Universitaria Senese, AOUS), Siena, Italy.

出版信息

Lung. 2021 Jun;199(3):281-288. doi: 10.1007/s00408-021-00449-3. Epub 2021 May 3.

Abstract

BACKGROUND

Galectins are proteins that bind β-galactosides such as N-acetyllactosamine present in N-linked and O-linked glycoproteins and that seem to be implicated in inflammatory and immune responses as well as fibrotic mechanisms. This preliminary study investigated serum galectins as clinical biomarkers in lung transplant patients with chronic lung allograft dysfunction (CLAD), phenotype bronchiolitis obliterans syndrome (BOS).

MATERIALS AND METHODS

Nineteen lung transplant patients [median age (IQR), 55 (45-62) years; 53% males] were enrolled in the study. Peripheral blood concentrations of galectins-1, 3 and 9 were determined with commercial ELISA kits.

RESULTS

Galectin-1 concentrations were higher in BOS than in stable LTX patients (p = 0.0394). In logistic regression analysis, testing BOS group as dependent variable with Gal-1 and 3 as independent variables, area under the receiver operating characteristics (AUROC) curve was 98.9% (NPV 90% and PPV 88.9%, p = 0.0003). With the stable LTX group as dependent variable and Gal-1, 3 and 9 as independent variables, AUROC was 92.6% (NPV 100% and PPV 90%, p = 0.0023). In stable patients were observed an inverse correlation of Gal-3 with DLCO% and KCO%, and between Gal-9 and KCO%.

CONCLUSION

Galectins-1, 3 and 9 are possible clinical biomarkers in lung transplant patients with diagnostic and prognostic meaning. These molecules may be directly implicated in the pathological mechanisms of BOS. The hypothesis that they could be new therapeutic targets in BOS patients is intriguing and also worth exploring.

摘要

背景

半乳糖凝集素是一种能与 N-乙酰乳糖胺等β-半乳糖苷结合的蛋白质,存在于 N-连接和 O-连接糖蛋白中,似乎与炎症和免疫反应以及纤维化机制有关。本初步研究调查了血清半乳糖凝集素作为慢性肺移植物功能障碍(CLAD)、表型闭塞性细支气管炎综合征(BOS)肺移植患者的临床生物标志物。

材料和方法

19 名肺移植患者[中位数(IQR),55(45-62)岁;53%为男性]纳入研究。使用商业 ELISA 试剂盒测定外周血半乳糖凝集素-1、3 和 9 的浓度。

结果

BOS 患者的半乳糖凝集素-1 浓度高于稳定 LTX 患者(p=0.0394)。在逻辑回归分析中,以 BOS 组为因变量,以 Gal-1 和 3 为自变量,受试者工作特征(ROC)曲线下面积(AUROC)为 98.9%(NPV 90%和 PPV 88.9%,p=0.0003)。以稳定 LTX 组为因变量,以 Gal-1、3 和 9 为自变量,AUROC 为 92.6%(NPV 100%和 PPV 90%,p=0.0023)。在稳定的患者中观察到 Gal-3 与 DLCO%和 KCO%之间存在负相关,以及 Gal-9 与 KCO%之间存在负相关。

结论

Gal-1、3 和 9 可能是肺移植患者具有诊断和预后意义的临床生物标志物。这些分子可能直接参与 BOS 的病理机制。这些分子可能成为 BOS 患者的新治疗靶点的假设很有趣,也值得进一步探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f03/8203538/01cbd2633616/408_2021_449_Fig1_HTML.jpg

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