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. 2021 Aug 23:12:724331.
doi: 10.3389/fimmu.2021.724331. eCollection 2021.

Functional Fc Gamma Receptor Gene Polymorphisms and Long-Term Kidney Allograft Survival

Markus Wahrmann  1 , Bernd Döhler  2 , Marie-Luise Arnold  3 , Sabine Scherer  2 , Katharina A Mayer  1 , Susanne Haindl  1 , Helmuth Haslacher  4 , Georg A Böhmig  1 , Caner Süsal  2
Affiliations

Functional Fc Gamma Receptor Gene Polymorphisms and Long-Term Kidney Allograft Survival

Markus Wahrmann et al. Front Immunol. .

Abstract

The functional Fc gamma receptor (FcγR) IIIA polymorphism FCGR3A-V/F158 was earlier suggested to determine the potential of donor-specific HLA antibodies to trigger microcirculation inflammation, a key lesion of antibody-mediated renal allograft rejection. Associations with long-term transplant outcomes, however, have not been evaluated to date. To clarify the impact of FCGR3A-V/F158 polymorphism on kidney transplant survival, we genotyped a cohort of 1,940 recipient/donor pairs. Analyzing 10-year death-censored allograft survival, we found no significant differences in relation to FCGR3A-V/F158. There was also no independent survival effect in a multivariable Cox model. Similarly, functional polymorphisms in two other activating FcγR, FCGR2A-H/R131 (FcγRIIA) and FCGR3B-NA1/NA2 (FcγRIIIB), were not associated with outcome. There were also no significant survival differences among patient subgroups at increased risk of rejection-related injury, such as pre-sensitized recipients (> 0% panel reactivity; n = 438) or recipients treated for rejection within the first year after transplantation (n = 229). Our study results suggest that the earlier shown association of FcγR polymorphism with microcirculation inflammation may not be strong enough to exert a meaningful effect on graft survival.

Keywords: Fc gamma receptor; allograft survival; anti-HLA antibodies; antibody-mediated rejection; kidney transplantation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Death-censored graft survival (A), overall graft survival (B), and patient survival (C) for genotypic groups of FCGR3A-V/F158 (total 1,940 recipients).
Figure 2
Figure 2
FCGR3A-V/F158 polymorphism in relation to 1-year serum creatinine [(A) total 1,676 recipients] and treated rejection episodes within the first year after transplantation [(B) total 1,010 recipients].
Figure 3
Figure 3
Death-censored graft survival among (A) 438 pre-sensitized recipients (panel reactivity > 0%) and (B) 229 recipients with treated rejection during the first-post-transplant year, in relation to FCGR3A-V/F158 genotype.
Figure 4
Figure 4
Impact of donor-derived FcγRIIIA polymorphism on death-censored graft survival (total 1,940 recipients).
See this image and copyright information in PMC

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