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 monocyte is an indicator for the severity of disease.
出处
《中华消化杂志》
CAS
CSCD
北大核心
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
