Original article. Correlation of FcγRIIIa polymorphisms and responses to rituximab in Thai population

Background: Rituximab is a chimeric IgG₁ monoclonal antibody against CD20, approved for the treatment of B-cell non-Hodgkin’s lymphoma (NHL). Antibody dependent cellular cytotoxicity (ADCC) has been suggested to be an important mechanism of rituximab via binding to the Fc gamma IIIa receptor (FcγRIIIa) on natural killer (NK) cells. FcγRIIIa has two expressed alleles that differ at amino acid position 158 in the extracellular domain, valine (V158) and phenylalanine (F158). These allelic variants have been demonstrated to differ in IgG₁ binding and ADCC. V/V homozygotes and V/F heterozygotes bind to IgG with higher affinity than F/F homozygotes.

Objectives: We identified the frequencies of FcγRIIIa polymorphism and investigate the correlation between FcγRIIIa polymorphism and rituximab responses, both in vitro and in vivo in Thai population.

Methods: The RFLP-Nested PCR and allele specific amplification was used to identify the FcγRIIIa polymorphism in the study. The correlation between FcγRIIIa polymorphism and rituximab responses, both in vitro and in vivo, was also studied.

Results: The distributions of FcγRIIIa-158 polymorphism in these subjects are V/V 40.26%, V/F 16.88%, and F/F 42.86%. Higher rituximab-induced Ramos cell cytotoxicity (mean 33.16%, 36.87%) was observed in the subjects with VV and VF genotypes, respectively. However, the lower cytotoxicity (mean 20.07%) was determined in subjects with FF genotype. As for the in vivo study, the NHL patients with V/V or V/F genotypes had a primary response as complete response; whereas, the NHL patients with F/F genotype had partial response.

Conclusion: FcγRIIIa polymorphism and the primary response in NHL patients tend to correlate. The higher number of patients is necessary for further study. These results provide useful information to understand beneficial response of rituximab as well as other IgG₁ therapeutic antibody in Thai patients.