Alloreactive adaptive natural killer cells in renal transplantation: potential contribution to allograft microvascular inflammation
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 mole...
| Autores: | , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universitat Pompeu Fabra |
| Repositorio: | Repositorio Digital de la UPF |
| OAI Identifier: | oai:repositori.upf.edu:10230/70976 |
| Acceso en línea: | http://hdl.handle.net/10230/70976 http://dx.doi.org/10.1016/j.ajt.2025.04.024 |
| Access Level: | acceso abierto |
| Palabra clave: | KIR-HLA-I mismatch Antibody-mediated rejection Killer cell immunoglobulin-like receptors Microvascular inflammation Natural killer cells Renal transplant |
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Alloreactive adaptive natural killer cells in renal transplantation: potential contribution to allograft microvascular inflammationAlari-Pahissa, ElisendaFederico-Vega, JudithAtaya Fernández, Michelle, 1993-Buxeda, AnnaBello-Rico, VíctorGimeno, JavierYélamos López, JoséAltadill, MireiaSanz-Ureña, SaraRiera, MartaBurballa Tàrrega, Carla, 1988-Chamoun, Betty OdettePérez-Sáez, María JoséRedondo Pachón, María DoloresVilches, CarlosCrespo Barrio, MartaLópez-Botet, M. (Miguel)KIR-HLA-I mismatchAntibody-mediated rejectionKiller cell immunoglobulin-like receptorsMicrovascular inflammationNatural killer cellsRenal transplantInhibitory 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).Elsevier202520252025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/70976http://dx.doi.org/10.1016/j.ajt.2025.04.024reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésAm J Transplant. 2025 Aug;25(8):1657-69info:eu-repo/grantAgreement/ES/2PE/PID2019-110609RB-C21info:eu-repo/grantAgreement/ES/2PE/PID2019-110609RB-C22© 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/openAccessoai:repositori.upf.edu:10230/709762026-06-12T07:21:37Z |
| dc.title.none.fl_str_mv |
Alloreactive adaptive natural killer cells in renal transplantation: potential contribution to allograft microvascular inflammation |
| title |
Alloreactive adaptive natural killer cells in renal transplantation: potential contribution to allograft microvascular inflammation |
| spellingShingle |
Alloreactive adaptive natural killer cells in renal transplantation: potential contribution to allograft microvascular inflammation Alari-Pahissa, Elisenda KIR-HLA-I mismatch Antibody-mediated rejection Killer cell immunoglobulin-like receptors Microvascular inflammation Natural killer cells Renal transplant |
| title_short |
Alloreactive adaptive natural killer cells in renal transplantation: potential contribution to allograft microvascular inflammation |
| title_full |
Alloreactive adaptive natural killer cells in renal transplantation: potential contribution to allograft microvascular inflammation |
| title_fullStr |
Alloreactive adaptive natural killer cells in renal transplantation: potential contribution to allograft microvascular inflammation |
| title_full_unstemmed |
Alloreactive adaptive natural killer cells in renal transplantation: potential contribution to allograft microvascular inflammation |
| title_sort |
Alloreactive adaptive natural killer cells in renal transplantation: potential contribution to allograft microvascular inflammation |
| dc.creator.none.fl_str_mv |
Alari-Pahissa, Elisenda Federico-Vega, Judith Ataya Fernández, Michelle, 1993- Buxeda, Anna Bello-Rico, Víctor Gimeno, Javier Yélamos López, José Altadill, Mireia Sanz-Ureña, Sara Riera, Marta Burballa Tàrrega, Carla, 1988- Chamoun, Betty Odette Pérez-Sáez, María José Redondo Pachón, María Dolores Vilches, Carlos Crespo Barrio, Marta López-Botet, M. (Miguel) |
| author |
Alari-Pahissa, Elisenda |
| author_facet |
Alari-Pahissa, Elisenda Federico-Vega, Judith Ataya Fernández, Michelle, 1993- Buxeda, Anna Bello-Rico, Víctor Gimeno, Javier Yélamos López, José Altadill, Mireia Sanz-Ureña, Sara Riera, Marta Burballa Tàrrega, Carla, 1988- Chamoun, Betty Odette Pérez-Sáez, María José Redondo Pachón, María Dolores Vilches, Carlos Crespo Barrio, Marta López-Botet, M. (Miguel) |
| author_role |
author |
| author2 |
Federico-Vega, Judith Ataya Fernández, Michelle, 1993- Buxeda, Anna Bello-Rico, Víctor Gimeno, Javier Yélamos López, José Altadill, Mireia Sanz-Ureña, Sara Riera, Marta Burballa Tàrrega, Carla, 1988- Chamoun, Betty Odette Pérez-Sáez, María José Redondo Pachón, María Dolores Vilches, Carlos Crespo Barrio, Marta López-Botet, M. (Miguel) |
| author2_role |
author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
KIR-HLA-I mismatch Antibody-mediated rejection Killer cell immunoglobulin-like receptors Microvascular inflammation Natural killer cells Renal transplant |
| topic |
KIR-HLA-I mismatch Antibody-mediated rejection Killer cell immunoglobulin-like receptors Microvascular inflammation Natural killer cells Renal transplant |
| description |
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. |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2025 2025 2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10230/70976 http://dx.doi.org/10.1016/j.ajt.2025.04.024 |
| url |
http://hdl.handle.net/10230/70976 http://dx.doi.org/10.1016/j.ajt.2025.04.024 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Am J Transplant. 2025 Aug;25(8):1657-69 info:eu-repo/grantAgreement/ES/2PE/PID2019-110609RB-C21 info:eu-repo/grantAgreement/ES/2PE/PID2019-110609RB-C22 |
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http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
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application/pdf application/pdf |
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Elsevier |
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Elsevier |
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reponame:Repositorio Digital de la UPF instname:Universitat Pompeu Fabra |
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