Functional Fc gamma receptor gene polymorphisms and donor-specific antibody-triggered microcirculation inflammation
Kainz A, Hidalgo LG, Eskandary F, Kozakowski N, Wahrmann M, Haslacher H, Oberbauer R, Heilos A, Spriewald BM, Halloran PF, Boehmig GA, Arnold M (2018)
Publication Type: Journal article
Publication year: 2018
Journal
DOI: 10.1111/ajt.14710
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 interferon gamma upon incubation with HLA antibody-coated cells as those expressing FCGR3A-F158 . FcγRIIA and FcγRIIIB polymorphisms were not associated with allograft morphology. Our data suggest that the presence of high-affinity FcγRIIIA variants may favor DSA-triggered microcirculation inflammation.
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Austria (AT)
Canada (CA)How to cite
APA:
Kainz, A., Hidalgo, L.G., Eskandary, F., Kozakowski, N., Wahrmann, M., Haslacher, H.,... Arnold, M. (2018). Functional Fc gamma receptor gene polymorphisms and donor-specific antibody-triggered microcirculation inflammation. American Journal of Transplantation. https://doi.org/10.1111/ajt.14710
MLA:
Kainz, A., et al. "Functional Fc gamma receptor gene polymorphisms and donor-specific antibody-triggered microcirculation inflammation." American Journal of Transplantation (2018).
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