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Effects of FCGRIII a ‐158V/F polymorphism on antibody‐dependent cellular cytotoxicity activity of adalimumab
Author(s) -
Kimura Koji,
Kobayashi Daigo,
Hatoyama Saori,
Yamamoto Mizuki,
Takayanagi Risa,
Yamada Yasuhiko
Publication year - 2017
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/apm.12754
Subject(s) - cytotoxicity , antibody , adalimumab , chemistry , microbiology and biotechnology , immunology , medicine , biology , biochemistry , tumor necrosis factor alpha , in vitro
The associations between the efficacy of IgG reagents and the FCGRIII a‐ 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 Fcγ RIII a 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 FCGRIII a ‐158V/F polymorphism.