乙型肝炎慢加急性肝功能衰竭患者免疫功能抑制与疾病严重程度的研究  

The study on the immune suppression with severity of HBV-related acute-on-chronic liver failure patients

作　　者：宫钰[1] 沈黎蔚[1] 王介非[2] 张正国[2] 章鹏[1] 李海[1] 

机构地区：[1]上海交通大学医学院附属仁济医院消化科上海市消化疾病研究所,200001 [2]复旦大学附属上海公共卫生临床中心

出　　处：《中华消化杂志》2011年第1期11-16,共6页Chinese Journal of Digestion

基　　金："十一五"国家高技术发展计划(863计划)重大项目，国家自然科学基金面上项目

摘　　要：目的探讨乙型肝炎慢加急性肝功能衰竭（ACLF）患者体内免疫功能抑制与疾病严重程度的关系。方法收集上海公共卫生临床中心2009年8月至2010年4月住院治疗的乙型肝炎ACLF患者27例（ACLF组），活动性慢性乙型肝炎患者28例（CHB组）和健康志愿者8名（对照组）的临床资料及外周血标本。以APACHEⅢ评分及肝性脑病程度作为反映疾病严重程度的量化指标。应用流式细胞术检测患者外周血中T淋巴细胞亚群的绝对计数和单核细胞表面人类白细胞抗原（HLA）-DR的表达量。采用CBA试剂盒检测患者血浆中促炎性细胞因子及抑炎性细胞因子[干扰素（IFN）-γ、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-2、IL4、Il-10]的水平。采用SPSS16．0软件进行数据统计。结果与CHB组和对照组相比，ACLF组患者抑炎性细胞因子IL-10含量显著增加（Z=-4．279，U=124，P〈0．01；Z=-3．871，U=9．5，P=0．0001），促炎性因子IFN-γ、TNF—α、IL-2、IL-4则处于检测值下限；外周血中单核细胞表面HlADR表达量显著下调（Z=-4．714，U=98，P％0．01；Z=-4．086，U=4，P〈0．01），HLA-DR表达量和APACHEⅢ评分存在显著负相关（R^2=0．2667，P=0．0167）；适应性免疫细胞CD4^＋T淋巴细胞绝对数量减少（Z=-4．411，U=116，P〈0．01；Z=-3．575，U=17，P=0．004）。结论乙型肝炎ACKLF患者的免疫系统存在单核细胞功能抑制、CD4^＋T细胞耗竭及高含量抑炎性细胞因子的免疫紊乱状态，单核细胞HLA—DR表达量持续下降是反映疾病严重程度的指标。Objective. To explore the association of immune suppression with the severity of HBV-related acute-on-chronic liver failure（ACLF） patients. Methods From August 2009 to April 2010 in Shanghai Public Health Clinical Center, the peripheral blood samples and clinical data of 27 HBV-related ACLF patients （ACLF group）, 28 patients with chronic active hepatitis B （CHB group） and 8 healthy individuals （Control group） were collected. APACHE m score and the grade of hepatic encephalopathy were as quantitative index to evaluate the severity degree of the disease. The absolute counts of the subsets of T lymphocytes and human leukocyte antigen （HLA）-DR expression on the surface of monocyte in patients＇ peripheral blood were examined by flow cytometry, the pro inflammatory cytokines and anti-inflammatory cytokines （IFN-γ, TNF-α, IL 2, IL-4, IL-10 ） in patients＇ plasma were detected by cytometric bead array （CBA） kit. The data was analyzed with SPSS 16.0 software. Results Compared with CHB group and control group, the level of anti-inflammatory cytokine IL-10 markedly increased in HBV-related ACLF patients （Z= -4. 279 ,U= 124, P=0.01; Z=-3. 871, U=9.5, P=0. 0001）, however the level of pro-inflammatory cytokines IFN-γ,TFN-α, IL-2 ,IL-4 in plasma were at low limit of detectable value. Meanwhile the expression quantity of HLA- DR on the peripheral blood monocytes significantly down-regulated （Z=- 4. 714, U= 98, P〈0.01; Z=-4. 086, U=4, P〈0. 01）, and there was negative correlation between HLA-DR expression quantity and APACHE III score （R2=0. 2667, P=0.0167）. In addition, the absolute counts of CD4^＋T lymphocytes in adaptive immune cells significantly decreased （Z=- 4. 411, U= 116, P〈 0.01; Z=-3. 575, U=17, P=0. 0004）. Conclusions The immune system of HBV related ACLF patients displays immune dysfunction like monocyte function inhibition; CD4＋T lymphocytes depletion and high level of anti-inflammatory cytokines, the persistent down-regulation of the HLA-DR expression on m

关 键 词：免疫系统疾病 肝功能衰竭 单核细胞 CD4阳性T淋巴细胞 细胞因子类 预后 流式细胞术 

分 类 号：R575.3[医药卫生—消化系统]