Correlation of FcγRIIIa Polymorphisms and the Response to Rituximab in Thai Population

Abstract

It has been reported that polymorphism in Fc gamma IIIa receptor (FcγRIIIa)
associates with antibody-dependent cellular cytotoxicity (ADCC) activity of rituximab, the
chimeric IgG1 monoclonal antibody against CD20. This antibody has been used for treatment
of several non-Hodgkin’s lymphomas originate from B cells and has ADCC as an important
mechanism of action. It is also known that genotype frequencies of FcγR polymorphisms
depend on race and ethnicity. In this study, we investigated Fc gamma IIIa receptor
(FcγRIIIa) genetic polymorphism at amino acid position 158 in Thai population. The nested
polymerase chain reaction-restriction fragment length polymorphism (nested PCR-RFLP)
was used to identify the FcγRIIIa genotypes of 60 healthy Thai male volunteers with
informed consent. The distributions of FcγRIIIa-158 polymorphisms in these subjects were as
follows: high binding genotypes (VV and VF), 55%; and low binding genotypes (FF), 45%.
The different response of these genotypes to ADCC activity of rituximab was also evaluated.
Rituximab-induced ADCC was performed by using PBMCs from 60 volunteers mentioned
before as effect cells and ramos cells which express CD20 as target cells in the present of
rituximab. High rituximab-induced Ramos cell cytotoxicity (mean rank 37.8%) was observed
in the present of PBMCs from subjects with VV and VF genotypes while lower cytotoxicity
(mean rank 21.6%) was determined in the present of PBMCs from subjects with FF
genotypes. Our results provide the distribution of FcγRIIIa polymorphisms in Thai population
which seems to differ from other Asian countries. This information should be useful for
considering to use many IgG therapeutic antibodies in Thai population.