1. T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation.
- Author
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Peereboom ETM, Matern BM, Tomosugi T, Niemann M, Drylewicz J, Joosten I, Allebes WA, van der Meer A, Hilbrands LB, Baas MC, van Reekum FE, Verhaar MC, Kamburova EG, Seelen MAJ, Sanders JS, Hepkema BG, Lambeck AJ, Bungener LB, Roozendaal C, Tilanus MGJ, Voorter CE, Wieten L, van Duijnhoven EM, Gelens MACJ, Christiaans MHL, van Ittersum FJ, Nurmohamed A, Lardy NM, Swelsen W, van der Pant KA, van der Weerd NC, Ten Berge IJM, Bemelman FJ, de Vries APJ, de Fijter JW, Betjes MGH, Roelen DL, Claas FH, Otten HG, Heidt S, van Zuilen AD, Kobayashi T, Geneugelijk K, and Spierings E
- Subjects
- Adult, Aged, Epitopes, T-Lymphocyte genetics, Female, Graft Rejection genetics, Graft vs Host Disease diagnosis, Graft vs Host Disease etiology, Graft vs Host Disease mortality, HLA Antigens genetics, Humans, Male, Middle Aged, Retrospective Studies, T-Lymphocytes metabolism, Tissue Donors, Transplant Recipients, Transplantation, Homologous, Treatment Failure, Young Adult, Epitopes, T-Lymphocyte immunology, Graft Rejection immunology, Graft Survival immunology, HLA Antigens immunology, Kidney Transplantation adverse effects, Kidney Transplantation methods, T-Lymphocytes immunology
- Abstract
CD4
+ T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4+ memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4+ memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome. In this study, the amount of T-cell epitopes shared between immunizing and donor HLA was used as a surrogate marker to evaluate the effect of donor-reactive CD4+ memory T-helper cells on the 10-year risk of death-censored kidney graft failure in 190 donor/recipient combinations using the PIRCHE-II algorithm. The T-cell epitopes of the initial theoretical immunizing HLA and the donor HLA were estimated and the number of shared PIRCHE-II epitopes was calculated. We show that the natural logarithm-transformed PIRCHE-II overlap score, or Shared T-cell EPitopes (STEP) score, significantly associates with the 10-year risk of death-censored kidney graft failure, suggesting that the presence of pre-transplant donor-reactive CD4+ memory T-helper cells might be a strong indicator for the risk of graft failure following kidney transplantation., Competing Interests: The authors of this manuscript have conflicts of interest to disclose. The UMC Utrecht has filed a patent application on the prediction of an alloimmune response against mismatched HLA. ES is listed as inventor on this patent. MN is employed by PIRCHE AG, which publishes the PIRCHE web-portal. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Peereboom, Matern, Tomosugi, Niemann, Drylewicz, Joosten, Allebes, van der Meer, Hilbrands, Baas, van Reekum, Verhaar, Kamburova, Seelen, Sanders, Hepkema, Lambeck, Bungener, Roozendaal, Tilanus, Voorter, Wieten, van Duijnhoven, Gelens, Christiaans, van Ittersum, Nurmohamed, Lardy, Swelsen, van der Pant, van der Weerd, ten Berge, Bemelman, de Vries, de Fijter, Betjes, Roelen, Claas, Otten, Heidt, van Zuilen, Kobayashi, Geneugelijk and Spierings.)- Published
- 2021
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