FcγRIIIa基因多态性对利妥昔单克隆抗体介导的NK细胞杀伤Raji细胞作用的影响  

Influence of FcγRIIIa Polymorphism on Rituximab-dependent NK Cell-mediated Cytotoxicity to Raji Cells

作　　者：屈钰华[1] 黎阳[1] 吴燕峰[2] 方建培[1] 黄绍良[1] 黄燕[1] 魏菁[3] 

机构地区：[1]中山大学孙逸仙纪念医院儿科,广东广州510120 [2]中山大学孙逸仙纪念医院生物治疗中心,广东广州510120 [3]中山大学孙逸仙纪念医院流式细胞仪室,广东广州510120

出　　处：《中国实验血液学杂志》2010年第5期1269-1274,共6页Journal of Experimental Hematology

基　　金：留学回国人员科研启动基金(2009年第36批)

摘　　要：由于FcγRIIIa的基因多态性可导致NK细胞上Fcγ受体(Fcgamma receptor,FcγR)与抗肿瘤单克隆抗体(monoclonal antibody,McAb)Fc段结合的亲和力不同,NK细胞以抗体依赖细胞介导的细胞毒性(antibody-depend-ent cell-mediated cytotoxicity,ADCC)对肿瘤细胞的杀伤能力也不同。本研究通过CFSE-PI双荧光染色法检测不同FcγRIIIa基因型的NK细胞对Raji细胞的ADCC效应强度,确定不同FcγRIIIa基因型的NK细胞所介导的AD-CC效应差异。用nest-PCR测定FcγRIIIa表型,用CFSE-PI双荧光染色法染色靶细胞(Raji细胞),用流式细胞术检测NK细胞上CD3-CD56+及FcγRIIIa的表达以及Raji细胞上CD20的表达,计算细胞毒性。结果表明:FcγRIIIa-158V/V基因型的NK细胞ADCC细胞毒性指数为(69.05±2.38)%,FcγRIIIa-158V/F基因型的NK细胞ADCC细胞毒性指数为(39.63±3.86)%,与V/V基因型相比,V/F基因型的NK细胞对Raji细胞的ADCC效应明显较弱,差异具有统计学意义(t=12.950,p=0.000)。结论:FcγRIIIa基因多态性可影响利妥昔单克隆抗体介导的NK细胞对Raji细胞的体外ADCC效应,以FcγRIIIa-158V/V基因型的NK细胞ADCC效应较FcγRIIIa-158V/F基因型的NK细胞ADCC效应强。Fcgamma receptor IIIa（FcγRIIIa） polymorphisms is considered to influence clinical response to therapeutic monoclonal antibody（McAb） in cancer,most people believe it can affect McAb binding,and McAb-dependent NK cell-mediated cytotoxicity.This study was purposed to determine the difference of antibody-dependent cell-mediated cytotoxicity（ADCC） effects mediated by different FcγRIIIa NK cells.The FcγRIIIa genotypes were detected by nest-PCR,the target cells（Raji cells） were stained with 5-（and 6-） carboxyfluorescein diacetate succinimidyl ester（CFSE）,cultured with effector cells with different FcγRIIIa genetypes,and finally stained with propidium iodide（PI）;the CD20 expression of Raji cells were tested by flow cytometry and cytotoxic index was calculated as well.The results indicated that the ADCC cytotoxic indexes of NK cells with FcγRIIIa-158V/V and FcγRIIIa-158V/F were 69.05±2.38% and 39.63±3.86% respectively,as compared with NK cells with FcγRIIIa158 V/V,ADCC effect of NK cells with FcγRIIIa-158 on Raji cells was obviously weakened with siguificant difference（p 0.05）.It is concluded that FcγRIIIa polymorphism can influence ADCC activity of NK cells,ADCC activity of NK cells with FcγRIIIa-158V/V is higher than that of NK cells with FcγRIIIa-158V/F.

关 键 词：FCΓRIIIA 抗体依赖细胞介导的细胞毒性 利妥昔单抗 肿瘤治疗 NK细胞 

分 类 号：R730.54[医药卫生—肿瘤]