Effects of FCGRIIIa‐158V/F polymorphism on antibody‐dependent cellular cytotoxicity activity of adalimumab

The associations between the efficacy of IgG reagents and the FCGRIIIa‐158V/F polymorphism (rs396991) have been investigated. Although the genotype frequencies in healthy Japanese have been reported, those have varied, as one study reported that the proportions of V/V, V/F, and F/F were 59.1%, 38.6%...

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Published in:APMIS : acta pathologica, microbiologica et immunologica Scandinavica microbiologica et immunologica Scandinavica, 2017-12, Vol.125 (12), p.1102-1107
Main Authors: Kimura, Koji, Kobayashi, Daigo, Hatoyama, Saori, Yamamoto, Mizuki, Takayanagi, Risa, Yamada, Yasuhiko
Format: Article
Language:English
Subjects:
Adalimumab
antibody‐dependent cellular cytotoxicity activity
Cytotoxicity
Fc receptors
FCGRIIIa‐158V/F polymorphism
Gene polymorphism
Genetic recombination
genotype frequency
Genotypes
Immunoglobulin G
Immunotherapy
Monoclonal antibodies
Polymorphism
Reagents
Toxicity
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Summary:The associations between the efficacy of IgG reagents and the FCGRIIIa‐158V/F polymorphism (rs396991) have been investigated. Although the genotype frequencies in healthy Japanese have been reported, those have varied, as one study reported that the proportions of V/V, V/F, and F/F were 59.1%, 38.6%, and 2.3%, respectively, while another study found that they were 4%, 44%, and 52%, respectively. However, there are no known investigations of the association between the antibody‐dependent cellular cytotoxicity (ADCC) activity of adalimumab (ADA), an IgG reagent, in combination with FcγRIIIa and the polymorphism. In this study, we analyzed healthy Japanese to clarify genotype frequency using a direct sequence method. In addition, we examined the association between the ADA‐mediated ADCC activity and the polymorphism. Our results showed that the frequencies of the V/V, V/F, and F/F genotypes in healthy Japanese were 9.2%, 39.8%, and 51.0%, respectively. The average activity of ADA‐mediated ADCC was 25.0%, 19.0%, and 13.3% in the V/V, V/F, and F/F genotypes, respectively. Then, the ADCC activity of V/V was significantly higher than that of F/F (p < 0.05) in therapeutic concentration. The differences in therapeutic effect of ADA among individuals can be explained, in part, by ADCC activity via the FCGRIIIa‐158V/F polymorphism.
ISSN:0903-4641
1600-0463
DOI:10.1111/apm.12754