Exosome-derived galectin-9 may be a novel predictor of rejection and prognosis after liver transplantation

外泌体来源的半乳糖凝集素-9预测肝移植术后排斥发生及预后（英文）

Acute cellular rejection(ACR) remains a major concern after liver transplantation.Predicting and monitoring acute rejection by non-invasive methods are very important for guiding the use of immunosuppressive drugs.Many studies have shown that exosomes and their contents are potential biomarkers for various liver diseases.Here,we identify and validate the role of exosomes and galectin-9 in ACR after liver transplantation.Exosomes were isolated from three sets of paired patients,with and without ACR,and the proteins within the exosomes were isolated and identified.Candidate proteins were then validated using a tissue microarray containing resected liver samples from 73 ACR and 63 non-rejection patients.Finally,protein expression and clinical manifestations were included in KaplanMeier survival and Cox regression analyses.Circulating exosomes were isolated from ACR and non-rejection patients and characterized using transmission electron microscopy and western blotting for CD63/CD81.Western blotting experiments revealed higher levels of galectin-9 protein in circulating exosomes from ACR recipients.Immunohistochemical analysis of the tissue microarray showed that the expression of galectin-9 in resected liver was significantly higher in the ACR group than in the non-rejection group(P<0.05).Higher levels of galectin-9 expression in resected livers were associated with poorer prognosis(P<0.05).Exosome-derived galectin-9 may be a novel predictor of rejection and prognosis after liver transplantation.

目的:外泌体及其内容物是各种肝脏疾病的潜在生物标志物。本研究探索外泌体及其内容物在肝移植排斥反应及预后中的作用。创新点:本研究发现外泌体及内含物半乳糖凝集素-9(galectin-9)在肝移植术后排斥及预后预测中发挥重要作用。方法:分别从急性排斥和肝功能稳定患者提取外泌体,进行分离、鉴定并检测其内含蛋白。候选蛋白通过在73个急性排斥病人和63个肝功能稳定病人切除肝的组织芯片中进行验证。最后将蛋白表达量和临床参数纳入Kaplan-Meier生存率和Cox回归分析。结论:外泌体来源的galectin-9可作为预测肝移植术后排斥发生及预后的生物学指标。