2026-04-13T01:09:52Zhttps://recercat.cat/oai/request
oai:recercat.cat:10230/709762025-08-03T21:14:25Zcom_2072_6col_2072_452952
RECERCAT author Alari-Pahissa, Elisenda author Federico-Vega, Judith author Ataya Fernández, Michelle, 1993- author Buxeda, Anna author Bello-Rico, Víctor author Gimeno, Javier author Yélamos López, José author Altadill, Mireia author Sanz-Ureña, Sara author Riera, Marta author Burballa Tàrrega, Carla, 1988- author Chamoun, Betty Odette author Pérez-Sáez, María José author Redondo Pachón, María Dolores author Vilches, Carlos author Crespo Barrio, Marta author López-Botet, M. (Miguel) 2025-07-23T07:11:23Z2025-07-23T07:11:23Z2025 Inhibitory killer cell immunoglobulin-like receptors (iKIRs) are randomly expressed by natural killer (NK) cell subsets and recognize motifs shared by HLA class-I (HLA-I) allotypes. Such interactions prevent NK cell autoreactivity while enhancing their response against cells lacking those HLA-I molecules (missing self), a situation defined in transplantation as iKIR-HLA-I mismatch (iKIR-MM), whose genotypic prediction has been associated with microvascular inflammation (MVI). Herein, we compared iKIR-MM in kidney transplant recipients with MVI ≥2 (n = 19) and controls with MVI ≤1 (n = 36). In parallel to genetic analysis of iKIR-MM, which was more frequent in MVI ≥2 patients, putative alloreactive iKIR-MM NK cells were defined by flow cytometry as NKG2A(-) cells bearing self-specific but lacking donor-specific iKIR. Although iKIR-MM NK cells were detected in both groups, their pretransplant numbers were higher in MVI ≥2 patients (median = 11.02, interquartile range = 0-58.31 vs median = 0, interquartile range = 0-9.46), especially in the presence of donor-specific antibodies or C4d, and correlated with MVI grade. Pretransplant, a subset of MVI ≥2 patients showed high proportions and numbers of oligoclonal iKIR-MM NK cells, which displayed an NKG2C(+) adaptive phenotype associated with cytomegalovirus infection. This pilot study provides a novel perspective on the contribution of iKIR-MM NK cells to MVI, with potential practical implications.J.F.V. had support from a grant awarded by the Catalan Transplantation Foundation. This study was supported by grants: “PI20/00090” and “PI23/00061”, funded by Instituto de Salud Carlos III (ISCIII) FIS and co-funded by the European Union (EU-FEDER); “PID2019-110609RB-C21” and “PID2019-110609RB-C22” (funded by Agencia Estatal de Investigación and cofunded by EU-FEDER; “P105/U/2018” (Fundació la Marató de TV3); “RD21/0005/0022” (National Network for Kidney Research RICORS2024, co-funded by Spanish Ministry of Health-ISCIIII and European Union-NextGenerationEU), Instituto de Salud Carlos III (ISCIII) RICORS program to RICORS 2040-Renal (RD24/0004/0003) funded by European Union – NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR), and a 2023 Nephrology Research grant (Spanish Society of Nephrology S.E.N). © 2025 The Authors. Published by Elsevier Inc. on behalf of American Society of Transplantation & American Society of Transplant Surgeons. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess KIR-HLA-I mismatch Antibody-mediated rejection Killer cell immunoglobulin-like receptors Microvascular inflammation Natural killer cells Renal transplant Alloreactive adaptive natural killer cells in renal transplantation: potential contribution to allograft microvascular inflammation info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion