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胆道闭锁肝脏CX3CR1^(+)T淋巴细胞的比例与肝纤维化及预后的相关性研究

Correlation between proportion of CX3CR1^(+)T lymphocyte and liver fibrosis and prognosis in biliary atresia
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摘要 目的探讨表达CX3C趋化因子受体1(CX3C chemokine receptor 1,CX3CR1)的T淋巴细胞(即CX3CR1^(+)T淋巴细胞)在不同儿童肝脏疾病中的表达情况,以及胆道闭锁肝组织浸润的表达CX3CR1的T淋巴细胞亚群与胆道闭锁患儿临床指标以及预后之间的关系。方法回顾性分析2019年1月至2020年6月在广州市妇女儿童医疗中心接受手术的24例胆道闭锁患儿临床资料,同时选取同期进行手术的胆总管囊肿20例(接受胆总管囊肿根治手术)、胆汁淤积症4例(术中胆道造影排除BA)、门静脉高压9例(行门静脉高压治疗手术)作为对照组。对24例胆道闭锁患儿肝脏标本进行肝纤维化评分。利用流式细胞技术对所有患儿肝脏中浸润的T淋巴细胞亚群进行分析。比较T淋巴细胞亚群在不同疾病患儿肝脏中的表达差异。采用Spearman检验对BA患儿肝脏中CX3CR1^(+)CD8^(+)T淋巴细胞比例与肝功能指标、BA肝纤维化评分分别进行相关性分析。对BA患儿随访2年,比较预后良好及预后不良患儿肝脏表达CX3CR1的T淋巴细胞比例。结果胆道闭锁组肝脏CD69-CX3CR1^(+)CD8^(+)T淋巴细胞比例为(7.91±8.81)%,低于胆总管囊肿患儿(21.53±13.85)%以及门静脉高压患儿(13.82±7.75)%,差异具有统计学意义(P<0.001,P=0.016);胆道闭锁组肝脏CD69-CX3CR1^(+)CD4^(+)T淋巴细胞比例为(3.96±5.39)%,低于胆总管囊肿患儿(8.76±9.16)%以及门静脉高压患儿(7.68±5.98)%,差异具有统计学意义(P=0.020,P=0.003)。胆道闭锁肝脏CX3CR1^(+)CD8^(+)T淋巴细胞比例与患儿γ-谷氨酰转肽酶水平及直接胆红素水平呈负相关,差异具有统计学意义(P=0.002和P=0.048)。胆道闭锁肝纤维化评分与肝脏中CX3CR1^(+)CD8^(+)T淋巴细胞比例及CX3CR1^(+)Ki67^(+)CD8^(+)T淋巴细胞比例呈负相关(P=0.025,P=0.030)。预后良好患儿肝脏中CX3CR1^(+)T淋巴细胞的比例较预后不良患儿高(P<0.05)。结论CX3CR1^(+)CD4^(+)T淋巴细胞和CX3CR1^(+)CD8^(+)T淋巴细胞可以反� Objective To explore the frequencies of CX3CR1 expressing T lymphocytes(CX3CR1^(+)T cell)in different liver diseases in children and to examine the relationship between proportion of CX3CR1-expressing T cells in liver and liver function parameters,fibrosis score and prognosis of children with biliary atresia(BA).Methods From January 2019 to June 2020,liver biopsies were harvested from BA children undergoing Kasai Procedure.And liver biopsies from children with choledochal cyst(CC),portal hypertension(PH)and neonatal cholestasis were set as controls.Liver fibrosis(LF)scores were performed on 24 liver specimens of BA children.The infiltrating T lymphocyte subpopulations in liver were analyzed by flow cytometry.The expression differences were examined for T lymphocyte subsets in liver of children with different diseases.Spearman's test was utilized for examining the correlation between the proportion of CX3CR1^(+)CD8^(+)T lymphocytes in liver of BA children,liver function parameters and LF score.During a follow-up period of 2 years,the proportion of T lymphocytes expressing CX3CR1 in liver was compared between children with good and poor prognosis.Results The proportion of CD69-CX3CR1^(+)CD8^(+)T lymphocytes in liver of BA group was(7.91±8.81)%.It was lower than that of CC children(21.53±13.85)%and PH children(13.82±7.75)%and the difference was statistically significant(P<0.001,P=0.016).The proportion of CD69-CX3CR1^(+)CD4^(+)T lymphocytes in liver of BA group was(3.96±5.39)%.It was lower than that of CC children(8.76±9.16)%and PH children(7.68±5.98)%and the difference was statistically significant(P=0.020,P=0.003).The proportion of CX3CR1^(+)CD8^(+)T lymphocytes in liver of BA children were correlated negatively with the levels of gamma-glutamyl transpeptidase(GGT)and direct bilirubin(P=0.002,P=0.048).LF score was correlated negatively with the proportions of CX3CR1^(+)CD8^(+)T and CX3CR1^(+)Ki67^(+)CD8^(+)T lymphocytes in liver(P=0.025,P=0.030).The proportion of CX3CR1^(+)T lymphocytes in liver of children w
作者 梁鉴坤 王晓蕾 萧云楠 宁禹 梁奇峰 任卉芳 白晓玲 张玉霞 徐艳慧 温哲 Liang Jiankun;Wang Xiaolei;Xiao Yunnan;Ning Yu;Liang Qifeng;Ren Huifang;Bai Xiaoling;Zhang Yuxia;Xu Yanhui;Wen Zhe(Department of Pediatric Surgery,Municipal Women&Children's Medical Center,Guangzhou 510623,China)
出处 《中华小儿外科杂志》 CSCD 北大核心 2023年第10期890-896,共7页 Chinese Journal of Pediatric Surgery
基金 广州市科技局基础研究计划项目(202102010149) 国家自然科学基金青年基金项目(NSFC82201892)。
关键词 胆道闭锁 趋化因子受体 肝纤维化 Biliary atresia Chemokine receptor Hepatic fibrosis
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