TY - JOUR
T1 - T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation
AU - Peereboom, Emma T. M.
AU - Matern, Benedict M.
AU - Tomosugi, Toshihide
AU - Niemann, Matthias
AU - Drylewicz, Julia
AU - Joosten, Irma
AU - Allebes, Wil A.
AU - van der Meer, Arnold
AU - Hilbrands, Luuk B.
AU - Baas, Marije C.
AU - van Reekum, Franka E.
AU - Verhaar, Marianne C.
AU - Kamburova, Elena G.
AU - Seelen, Marc A. J.
AU - Sanders, Jan Stephan
AU - Hepkema, Bouke G.
AU - Lambeck, Annechien J.
AU - Bungener, Laura B.
AU - Roozendaal, Caroline
AU - Tilanus, Marcel G. J.
AU - Voorter, Christien E.
AU - Wieten, Lotte
AU - van Duijnhoven, Elly M.
AU - Gelens, Mariëlle A. C. J.
AU - Christiaans, Maarten H. L.
AU - van Ittersum, Frans J.
AU - Nurmohamed, Azam
AU - Lardy, Neubury M.
AU - Swelsen, Wendy
AU - van der Pant, Karlijn A.
AU - van der Weerd, Neelke C.
AU - ten Berge, Ineke J. M.
AU - Bemelman, Fréderike J.
AU - de Vries, Aiko P. J.
AU - de Fijter, Johan W.
AU - Betjes, Michiel G. H.
AU - Roelen, Dave L.
AU - Claas, Frans H.
AU - Otten, Henny G.
AU - Heidt, Sebastiaan
AU - van Zuilen, Arjan D.
AU - Kobayashi, Takaaki
AU - Geneugelijk, Kirsten
AU - Spierings, Eric
N1 - Funding Information:
This study was supported by research funding from the Dutch Kidney Foundation project code CP12.23 "Risk assessment of kidney graft failure by HLA antibody profiling" and project code CP1801 “Prediction of Kidney Graft Survival by Immune Profiling - Towards Clinical Application in Personalized Medicine”, by research funding from EU Horizon 2020 for the ULISES project, code 899708, and by research funding from the International HLA and Immunogenetics Workshop Foundation.
Publisher Copyright:
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.
PY - 2021/11/18
Y1 - 2021/11/18
N2 - 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.
AB - 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.
KW - HLA antigens
KW - PIRCHE-II
KW - T-cell epitope
KW - T-cell memory
KW - graft failure
KW - kidney transplantation
KW - shared T-cell epitopes
UR - https://www.scopus.com/pages/publications/85120553800
U2 - 10.3389/fimmu.2021.784040
DO - 10.3389/fimmu.2021.784040
M3 - Article
C2 - 34868064
SN - 1664-3224
VL - 12
SP - 784040
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 784040
ER -