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. 2025 May;29(5):681-689.
doi: 10.1007/s10157-024-02610-7. Epub 2025 Jan 13.

Impact of Fc-gamma receptor IIIA polymorphism on late-onset neutropenia and clinical outcomes in kidney transplant recipients following rituximab induction therapy

Yuki Tashiro  1 , Yoji Hyodo  2 , Satoshi Kitamura  1 , Takuya Fujimoto  3 , Takahito Endo  1 , Shun Nishioka  1 , Naoki Yokoyama  1 , Takuto Hara  1 , Koji Chiba  1 , Hideaki Miyake  1
Affiliations

Impact of Fc-gamma receptor IIIA polymorphism on late-onset neutropenia and clinical outcomes in kidney transplant recipients following rituximab induction therapy

Yuki Tashiro et al. Clin Exp Nephrol. 2025 May.

Abstract

Background: This study aimed to investigate the association between the Fc-gamma receptor IIIA (FCGR3A) 158 polymorphism and clinical outcomes in kidney transplantation (KTx) patients. Specifically, we focused on late-onset neutropenia (LON) in ABO-incompatible (ABOi) or HLA-incompatible (HLAi) KTx recipients who underwent rituximab (RTx) desensitization therapy.

Methods: FCGR3A 158F/V polymorphisms were identified in 85 ABOi or HLAi KTx recipients who underwent RTx desensitization at our institution between April 2008 and October 2021. We analyzed these polymorphism groups in relation to their preoperative background and incidence of LON, infection, and rejection. In addition, we examined the risk factors for LON development.

Results: The following FCGR3A 158F/V polymorphisms were identified: FF genotype (n = 45); FV genotype (n = 36), and VV genotype (n = 4). LON occurred in 25 out of 85 recipients within 1 year after KTx, significantly more frequently in patients with the FCGR3A FV + VV genotype (17/40) than in those with the FF genotype (8/45) (p = 0.01). A multivariate analysis identified the V-allele as an independent risk factor for LON (OR, 4.03; 95% CI, 1.38-11.73, p = 0.01). However, there were no significant differences in the incidence rates of post-transplant infection and rejection between the FF and FV + VV genotypes.

Conclusion: Recipients with the FCGR3A 158 V-allele were identified as having a higher risk of developing LON following KTx with RTx desensitization therapy. However, the presence of this V-allele did not affect the safety or efficacy of RTx desensitization before KTx.

Keywords: Fc-gamma receptor IIIa; Kidney transplantation; Neutropenia; Polymorphisms; Rituximab.

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Conflict of interest statement

Declarations. Conflict of interest: The authors have declared that no conflict of interest exists. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board (IRB) of Kobe University Hospital (IRB approval number B220142) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The studies were in accordance with the Declaration of Istanbul. Informed consent: Written informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
The 10-year graft survival. The survival rate was determined using the Kaplan–Meier method. The 10-year graft survival rates were 92.6% and 84.0% in recipients with the FCGR3A 158FF-genotype and FV + VV-genotype, respectively (p = 0.41)
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