The Impact of HLA-DQαβ Heterodimer Mismatch on Living Donor Kidney Allograft Outcomes.

Autor:	Charnaya O; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD., Ishaque T; Center for Surgical and Transplant Applied Research, NYU Langone Health, New York, NY., Hallett A; Department of Surgery, Thomas Jefferson University, Philadelphia, PA., Morris GP; Department of Pathology, University of California San Diego, La Jolla, CA., Coppage M; Department of Pathology and Laboratory Medicine, University of Rochester, Rochester, NY., Schmitz JL; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC., Timofeeva O; Pathology Academic Department, Georgetown University School of Medicine and MedStar Georgetown University Hospital, Washington, DC., Lázár-Molnár E; Department of Pathology, University of Utah, Salt Lake City, UT., Zhang A; Department of Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH., Krummey S; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD., Hidalgo L; Division of Transplantation, University of Wisconsin System, Madison, WI., Segev DL; Center for Surgical and Transplant Applied Research, NYU Langone Health, New York, NY., Tambur AR; Department of Surgery, Comprehensive Transplant Center, Northwestern University, Chicago, IL., Massie AB; Center for Surgical and Transplant Applied Research, NYU Langone Health, New York, NY.
Jazyk:	angličtina
Zdroj:	Transplantation [Transplantation] 2024 Sep 05. Date of Electronic Publication: 2024 Sep 05.
DOI:	10.1097/TP.0000000000005198
Abstrakt:	Background: HLA-DQ mismatch has been identified as a predictor of de novo donor-specific HLA antibody formation and antibody-mediated rejection. There are insufficient data to guide the incorporation of DQ mismatch into organ allocation decisions. Methods: We used a retrospective longitudinal cohort of adult living donor kidney transplant recipients from 11 centers across the United States for whom high-resolution class II typing was available. HLA-DQαβ heterodimer allele mismatch was quantified for all donor-recipient pairs, and outcome data were obtained through linkage with the Scientific Registry of Transplant Recipients. Results: We studied 3916 donor-recipient pairs. Recipient characteristics were notable for a median age of 51 (38-61) y, primarily unsensitized, with 74.5% of the cohort having 0% calculated panel-reactive antibody, and 60.4% with private insurance, for a median follow-up time of 5.86 y. We found that the HLA-DQαβ allele and HLA-DR antigen mismatch were each individually associated with an increased hazard of all-cause graft failure (adjusted hazard ratio [aHR] DQ = 1.03 1.14 1.28; aHR DR = 1.03 1.15 1.328), death-censored graft failure (aHR DQ =1.01 1.19 1.40; aHR DR = 0.099 1.18 1.39), and rejection. Having 2 HLA-DQαβ allele mismatches further increased the hazard of rejection even when controlling for HLA-DR mismatch (aHR 1.03 1.68 2.74). Conclusions: HLA-DQαβ allele mismatch predicted allograft rejection even when controlling for HLA-DR antigen mismatch and were both independently associated with increased risk of graft failure or rejection in adult living kidney transplant recipients. Given the strong burden of disease arising from the HLA-DQ antibody formation, we suggest that HLA-DQαβ should be prioritized over HLA-DR in donor selection. Competing Interests: G.P.M. received research support from Thermo Fisher/One Lambda, CareDx, and PIRCHE AG, as well as travel support to scientific meetings from Thermo Fisher. The other authors declare no conflicts of interest. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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