慢性乙型肝炎患者外周血B淋巴细胞亚群的变化特征及临床意义  

Characteristics and clinical significance of changes in peripheral blood B lymphocyte subsets in patients with chronic hepatitis B

作　　者：汪海燕 鲍春梅 冯芷倩 王静[1,2] 李亚群 李静 王红敏 唐莉莉[2,5] 杨涛 徐若男 王福生 Wang Hai-Yan;Bao Chun-Mei;Feng Zhi-Qian;Wang Jing;Li Ya-Qun;Li Jing;Wang Hong-Min;Tang Li-Li;Yang Tao;Xu Ruo-Nan;Wang Fu-Sheng(The First Affiliated Hospital of University of Science and Technology of China,Hefei,Anhui 230001,China;Senior Department of Infectious Diseases,the Fifth Medical Center of PLA General Hospital,National Clinical Research Center for Infectious Diseases,Beijing 100039,China;Clinical Laboratory Medical Center,the Fifth Medical Center of PLA General Hospital,Beijing 100039,China;The Second School of Clinical Medicine,Southern Medical University,Guangzhou,Guangdong 510515,China;Peking University 302 Clinical Medical School,Beijing 100039,China)

机构地区：[1]中国科学技术大学附属第一医院,安徽合肥230001 [2]解放军总医院第五医学中心感染病医学部,国家感染性疾病临床医学研究中心,北京100039 [3]解放军总医院第五医学中心临床检验医学中心,北京100039 [4]南方医科大学第二临床医学院,广东广州510515 [5]北京大学302临床医学院,北京100039

出　　处：《解放军医学杂志》2024年第5期511-518,共8页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金创新群体项目(81721002)。

摘　　要：目的观察慢性乙型肝炎(CHB)患者外周血B淋巴细胞(B细胞)亚群的变化特征,并探讨其临床意义。方法收集2022年7-10月在解放军总医院第五医学中心就诊的37例CHB未治疗患者的外周血标本,同时收集18名接种过乙肝疫苗的健康人外周血标本作为健康对照(HC),并收集研究对象的年龄、HBV DNA病毒载量、HBsAg定量、HBeAg半定量、谷丙转氨酶(ALT)、谷草转氨酶(AST)及AST/ALT比值等临床指标。采用多色流式细胞术检测并比较两组外周血B细胞及各亚群的频率、表型及功能标志物的变化特征,并探究其与临床指标之间的相关性。结果B细胞各亚群频率分析显示,与HC组比较,CHB组整体B细胞、过渡B细胞及幼稚B细胞频率均降低(P<0.05),而成熟B细胞、记忆B细胞、非典型记忆B细胞及激活记忆B细胞频率均升高(P<0.01);两组静息记忆B细胞频率比较,差异无统计学意义(P>0.05)。B细胞各亚群功能分析显示,与HC组比较,CHB组整体B细胞、成熟B细胞、记忆B细胞、幼稚B细胞、激活记忆B细胞、非典型记忆B细胞及静息记忆B细胞的CD79b表达水平均升高(P<0.05);此外,CHB组非典型记忆B细胞的程序性死亡受体1(PD-1)表达水平也高于HC组(P<0.05)。相关性分析显示,CHB组整体B细胞频率与年龄呈负相关(r=-0.39,P<0.05),且整体B细胞、成熟B细胞、过渡B细胞、记忆B细胞、幼稚B细胞的PD-1表达水平与年龄均呈正相关(r>0.36,P<0.05)。结论慢性HBV感染导致CHB患者外周血部分B细胞的频率及功能发生耗竭,而年龄是导致CHB患者体液免疫功能下降的潜在危险因素。Objective To analyze the changes of B lymphocyte(B cells)subsets in peripheral blood of patients with chronic hepatitis B(CHB)and to explore its clinical significance.Methods Peripheral blood samples were collected from 37 treatment�naïve CHB patients who were admitted to the Fifth Medical Center of PLA General Hospital from July 2022 to October 2022,and peripheral blood samples collected from 18 healthy individuals who have received the hepatitis B vaccine as healthy controls(HC).The study subjects'clinical indexes such as age,HBV DNA viral load,HBsAg quantification,HBeAg semi quantification,ALT,AST,and AST/ALT ratio were collected.The change characteristics of the frequency,phenotypic and functional markers of peripheral blood B lymphocytes and their subsets were compared between CHB and HC.Using multi-color flow cytometry,and the correlation between them and clinical indexes was analyzed.Results Frequency analysis of each subset of B cells showed that compared with HC,the frequency of total B cells,transitional B cells and naive B cells was decreased(P<0.05),while the frequency of mature B cells,memory B cells,atypical memory B cells and activated memory B cells was increased in CHB patients(P<0.01).And there was no significant difference in the frequency of resting memory B cells between the two groups(P>0.05).The results of functional analysis showed that compared with HC,the expression levels of CD79b on total B cells,mature B cells,memory B cells,naive B cells,activated memory B cells,atypical memory B cells and resting memory B cells in CHB patients were increased(P<0.05).The expression level of programmed cell death protein-1(PD-1)on atypical memory B cells in CHB patients was also higher than that in HC group(P<0.05).The results of correlation analysis showed that the frequency of total B cells in CHB patients was slightly negatively correlated with age(r=-0.39,P<0.05),while the expression of programmed death-1(PD-1)on total B cells,mature B cells,transitional B cells,memory B cells and naive B cells

关 键 词：乙型肝炎病毒 乙型肝炎 慢性 B-淋巴细胞 免疫 体液 外周血 

分 类 号：R512.62[医药卫生—内科学]