利妥昔单抗对多发性硬化症复发期患者外周血NK细胞 功能  

Regulation of NK cell function by rituximab in peripheral blood of patients with multiple sclerosis at relapse stage

作　　者：何菁菁 晏世荣 吴通前 杨秀兰 沈雪 余芳 HE Jingjing;YAN Shirong;WU Tongqian;YANG Xiulan;SHEN Xue;YU Fang(Department of Clinical Microbiology and Immunology,School of Clinical Laboratory Science,Guizhou Medical University,Guiyang 550004,Guizhou,China;Clinical Laboratory Center,the Affiliated Hospital of Guizhou Medical University,Guiyang 550004,Guizhou,China;Clinical Research Center,the Affiliated Hospital of Guizhou Medical University,Guiyang 550004,Guizhou,China)

机构地区：[1]贵州医科大学医学检验学院临床微生物及免疫学教研室,贵州贵阳550004 [2]贵州医科大学附属医院临床检验中心,贵州贵阳550004 [3]贵州医科大学附属医院临床研究中心,贵州贵阳550004

出　　处：《贵州医科大学学报》2024年第5期691-696,共6页Journal of Guizhou Medical University

基　　金：国家自然科学基金项目(81760294,82260324,82201968);贵州省基础研究计划项目(黔科合基础-ZK〔2023〕一般394,黔科合基础-ZK〔2023〕一般398);贵州省卫健委科学技术基金项目(gzwkj2022-064)。

摘　　要：目的观察利妥昔单抗对多发性硬化症(MS)复发期患者外周血NK细胞活化及ADCC功能的影响及机制。方法选取MS复发期病例(n=28),并将无自身免疫疾病及重大感染疾病的受试者作为健康对照组(n=25),提取两组被检者外周血单个核细胞(PBMCs),检测利妥昔单抗处理前后B细胞、自然杀伤细胞(NK)细胞比例及NK细胞活化水平;建立PBMCs与人慢性髓源白血病细胞系K562细胞直接接触共培养体系,检测利妥昔单抗处理后NK细胞抗体依赖细胞介导细胞毒性作用(ADCC)的效应因子释放。结果利妥昔单抗能诱导MS复发期组和健康对照组外周血中B细胞和NK细胞比例显著下调,且能诱导健康对照组的NK细胞活化及ADCC功能的显著上调,但对MS复发期患者NK细胞的活化及ADCC功无明显影响。结论利妥昔单抗可诱导MS复发期患者B细胞及NK细胞比例下调,但对NK细胞的活化及其ADCC功能无明显影响。Objective To observe the effect of rituximab(RTX)on NK cell activation and antibody-dependent cellular cytotoxicity(ADCC)activity of NK cells in the peripheral blood of patients with multiple sclerosis(MS)at relapse stage and its mechanism.Methods A total of 28 patients with MS at relapse stage were recruited as a case group.Subjects without autoimmune diseases or major infectious diseases were selected as a healthy control group(n=25).Peripheral blood mononuclear cells(PBMCs)were prepared from two groups to detect the proportions of B cells and natural killer(NK)cells and NK cell activation level before and after treatment with rituximab.Direct contact co-culture system was established between PBMCs and K562 cells to detect the release of effector factors from NK cell ADCC after RTX treatment.Results Rituximab induced a significant downregulation of the proportions of B cells and NK cells in the peripheral blood in case and healthy control groups,induced NK cell activation,upregulated ADCC function in healthy control group,but did not remarkably affect NK cell activation and ADCC function in case group.Conclusion Rituximab can induce the downregulation of the proportions of B cells and NK cells in patients with MS at relapse stage,but has no significant effect on the activation of NK cells and their ADCC function.

关 键 词：多发性硬化症 利妥昔单抗 自然杀伤细胞 细胞活化 效应因子 抗体依赖的细胞介导的细胞毒性作用 

分 类 号：R744.5[医药卫生—神经病学与精神病学]