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Epitopes as characterized by antibody-verified eplet mismatches determine risk of kidney transplant loss.
Sapir-Pichhadze, Ruth; Zhang, Xun; Ferradji, Abdelhakim; Madbouly, Abeer; Tinckam, Kathryn J; Gebel, Howard M; Blum, Daniel; Marrari, Marilyn; Kim, S Joseph; Fingerson, Stephanie; Bashyal, Pradeep; Cardinal, Héloïse; Foster, Bethany J.
Afiliación
  • Sapir-Pichhadze R; Division of Nephrology, Royal Victoria Hospital, McGill University Health Centre, Montreal, Quebec, Canada; The Multi Organ Transplant Program, Royal Victoria Hospital, McGill University Health Centre, Montreal, Quebec, Canada; Centre for Outcomes Research and Evaluation (CORE), McGill University He
  • Zhang X; Centre for Outcomes Research and Evaluation (CORE), McGill University Health Centre, Montreal, Quebec, Canada.
  • Ferradji A; Research Institute, McGill University Health Centre, Montreal, Quebec, Canada.
  • Madbouly A; Bioinformatics Research, Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota, USA.
  • Tinckam KJ; Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada; The Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada; Division of Nephrology, Department of Medicine, University of Toronto, Toronto, Ontario
  • Gebel HM; Department of Pathology, Emory University, Atlanta, Georgia, USA.
  • Blum D; Division of Nephrology, St Michael's Hospital, Toronto, Ontario, Canada.
  • Marrari M; Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
  • Kim SJ; Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada; The Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada; Division of Nephrology, Department of Medicine, University of Toronto, Toronto, Ontario
  • Fingerson S; Bioinformatics Research, Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota, USA.
  • Bashyal P; Bioinformatics Research, Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota, USA.
  • Cardinal H; Montreal University Hospital Center, Montreal, Quebec, Canada.
  • Foster BJ; Centre for Outcomes Research and Evaluation (CORE), McGill University Health Centre, Montreal, Quebec, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada; Montreal Children's Hospital, McGill University Health Centre, Montreal, Queb
Kidney Int ; 97(4): 778-785, 2020 04.
Article en En | MEDLINE | ID: mdl-32059998
To optimize strategies that mitigate the risk of graft loss associated with HLA incompatibility, we evaluated whether sequence defined HLA targets (eplets) that result in donor-specific antibodies are associated with transplant outcomes. To define this, we fit multivariable Cox proportional hazard models in a cohort of 118 382 United States first kidney transplant recipients to assess risk of death-censored graft failure by increments of ten antibody-verified eplet mismatches. To verify robustness of our findings, we conducted sensitivity analysis in this United States cohort and assessed the role of antibody-verified eplet mismatches as autonomous predictors of transplant glomerulopathy in an independent Canadian cohort. Antibody-verified eplet mismatches were found to be independent predictors of death-censored graft failure with hazard ratios of 1.231 [95% confidence interval 1.195, 1. 268], 1.268 [1.231, 1.305] and 1.411 [1.331, 1.495] for Class I (HLA-A, B, and C), -DRB1 and -DQB1 loci, respectively. To address linkage disequilibrium between HLA-DRB1 and -DQB1, we fit models in a subcohort without HLA-DQB1 eplet mismatches and found hazard ratios for death-censored graft failure of 1.384 [1.293, 1.480] for each additional antibody-verified HLA-DRB1 eplet mismatch. In a subcohort without HLA-DRB1 mismatches, the hazard ratio was 1.384 [1.072, 1.791] for each additional HLA-DQB1 mismatch. In the Canadian cohort, antibody-verified eplet mismatches were independent predictors of transplant glomerulopathy with hazard ratios of 5.511 [1.442, 21.080] for HLA-DRB1 and 3.640 [1.574, 8.416] for -DRB1/3/4/5. Thus, donor-recipient matching for specific HLA eplets appears to be a feasible and clinically justifiable strategy to mitigate risk of graft loss.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Trasplante de Riñón Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Humans País/Región como asunto: America do norte Idioma: En Revista: Kidney Int Año: 2020 Tipo del documento: Article

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Trasplante de Riñón Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Humans País/Región como asunto: America do norte Idioma: En Revista: Kidney Int Año: 2020 Tipo del documento: Article