FCGR3A-158 polymorphism influences the biological response to infliximab in Crohn's disease through affecting the ADCC activity

Rintaro Moroi, Katsuya Endo, Yoshitaka Kinouchi, Hisashi Shiga, Yoichi Kakuta, Masatake Kuroha, Yoshitake Kanazawa, Yosuke Shimodaira, Takahiko Horiuchi, Seiichi Takahashi, Tooru Shimosegawa

Research output: Contribution to journalArticle

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Abstract

An association between FCGR3A-158 V/F polymorphism and biological responses to infliximab has been reported in Crohn's disease (CD) in Western countries. However, little is known about the mechanism by which gene polymorphism affects the responses to infliximab. The aims of this study were to confirm the association in Japanese CD patients and to reveal the effect of gene polymorphism on biological responses to infliximab. Japanese CD patients were examined retrospectively at weeks 8 and 30. Clinical and biological responses were assessed by the Crohn's disease activity index and C-reactive protein levels, respectively. The infliximab-binding affinity of natural killer (NK) cells from FCGR3A-158 V/V, V/F and F/F donors was examined. Infliximab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) activities were also determined using transmembrane TNF-α-expressing Jurkat T cells as target cells and peripheral blood mononuclear cells (PBMCs) from V/V, V/F and F/F donors as effector cells. Biological responses at week 8 were statistically higher in V/V patients, whereas no significant differences were observed in either clinical responses at weeks 8 and 30 or biological responses at week 30 among the three genotypes. NK cells and PBMCs from V/V patients also showed higher infliximab-binding affinity and infliximab-mediated ADCC activity, respectively. Our results suggest that FCGR3A-158 polymorphism is a predicting factor of biological responses to infliximab in the early phases. FCGR3A-158 polymorphism was also found to affect the infliximab-binding affinity of NK cells and infliximab-mediated ADCC activity in vitro, suggesting that an effect on ADCC activity influences biological responses to infliximab in CD patients.

Original languageEnglish
Pages (from-to)265-271
Number of pages7
JournalImmunogenetics
Volume65
Issue number4
DOIs
Publication statusPublished - Jan 1 2013

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Antibody-Dependent Cell Cytotoxicity
Crohn Disease
Natural Killer Cells
Blood Cells
Infliximab
Tissue Donors
Jurkat Cells
Biological Factors
C-Reactive Protein
Genes
Genotype

All Science Journal Classification (ASJC) codes

  • Immunology
  • Genetics

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FCGR3A-158 polymorphism influences the biological response to infliximab in Crohn's disease through affecting the ADCC activity. / Moroi, Rintaro; Endo, Katsuya; Kinouchi, Yoshitaka; Shiga, Hisashi; Kakuta, Yoichi; Kuroha, Masatake; Kanazawa, Yoshitake; Shimodaira, Yosuke; Horiuchi, Takahiko; Takahashi, Seiichi; Shimosegawa, Tooru.

In: Immunogenetics, Vol. 65, No. 4, 01.01.2013, p. 265-271.

Research output: Contribution to journalArticle

Moroi, R, Endo, K, Kinouchi, Y, Shiga, H, Kakuta, Y, Kuroha, M, Kanazawa, Y, Shimodaira, Y, Horiuchi, T, Takahashi, S & Shimosegawa, T 2013, 'FCGR3A-158 polymorphism influences the biological response to infliximab in Crohn's disease through affecting the ADCC activity', Immunogenetics, vol. 65, no. 4, pp. 265-271. https://doi.org/10.1007/s00251-013-0679-8
Moroi, Rintaro ; Endo, Katsuya ; Kinouchi, Yoshitaka ; Shiga, Hisashi ; Kakuta, Yoichi ; Kuroha, Masatake ; Kanazawa, Yoshitake ; Shimodaira, Yosuke ; Horiuchi, Takahiko ; Takahashi, Seiichi ; Shimosegawa, Tooru. / FCGR3A-158 polymorphism influences the biological response to infliximab in Crohn's disease through affecting the ADCC activity. In: Immunogenetics. 2013 ; Vol. 65, No. 4. pp. 265-271.
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