[Influence of FcγRIIIa polymorphism on rituximab-dependent NK cell-mediated cytotoxicity to Raji cells].
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 genotypes, 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 significant 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.
Department of Pediatrics, Sun Yet-Sen Memorial Hospital, Sun Yet-Sen University, Guangzhou 510120, Guangdong Province, China.
Yu-Hua
YH
Qu
Yang
Y
Li
Yan-Feng
YF
Wu
Jian-Pei
JP
Fang
Shao-Liang
SL
Huang
Yan
Y
Huang
Jing
J
Wei
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D002460:Cell Line; D005838:Genotype; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects*; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics*; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C496124:FCGR3A protein, human; D017452:Receptors, IgG; D000069283:Rituximab