Functional Fc gamma receptor gene polymorphisms and donor-specific antibody-triggered microcirculation inflammation

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Marie-Luise ArnoldGeorg A Böhmig

Abstract

Fc-dependent effector mechanisms may contribute to antibody-mediated rejection (ABMR), and distinct gene polymorphisms modifying the function of Fc gamma receptors (FcγRs) may influence the capability of donor-specific antibodies (DSAs) to trigger inflammation. To evaluate the relevance of functional FcγR variants in late ABMR, 85 DSA-positive kidney allograft recipients, who were recruited upon antibody screening of 741 prevalent patients, were genotyped for polymorphisms in FcγRIIA (FCGR2A-H/R131 ; rs1801274), FcγRIIIA (FCGR3A-V/F158 ; rs396991), and FcγRIIIB (FCGR3B-neutrophil antigen 1 ([NA1]/NA2; rs35139848). Individuals with high-affinity FCGR3A-V158 alleles (V/V158 or V/F158 ) showed a higher rate (and extent) of peritubular capillaritis (ptc) in protocol biopsies than homozygous carriers of the lower-affinity allele (ptc score ≥1: 53.6% vs 25.9%; P = .018). Associations were independent of C1q-binding to DSA or capillary C4d. In parallel, there was a trend toward increased macrophage- and injury-repair response-associated transcript subsets. Kidney function over 24 months, however, was not different. In support of a functional role of FcγRIIIA polymorphism, NK92 cells expressing FCGR3A-V158 produced >2 times as much int...Continue Reading

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Citations

Apr 24, 2020·Transplant Infectious Disease : an Official Journal of the Transplantation Society·Jungyeon MoonDavid I Min
Apr 29, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Anat R TamburPeter Nickerson
Nov 21, 2018·International Reviews of Immunology·Pernille Koefoed-Nielsen, Bjarne Kuno Møller
Jun 17, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Peter W Nickerson
Jan 9, 2021·Journal of the American Society of Nephrology : JASN·Luis G Hidalgo
Feb 16, 2021·International Journal of Immunogenetics·Megan A O'Neill, Luis G Hidalgo
Sep 10, 2021·Frontiers in Immunology·Markus WahrmannCaner Süsal
Jul 9, 2021·Kidney Research and Clinical Practice·Yohan ParkChul Woo Yang

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