PUBLISHED BY
Peereboom, Emma T. M.; Matern, Benedict M.; Tomosugi, Toshihide; Niemann, Matthias; Drylewicz, Julia; Joosten, Irma; Allebes, Wil A.; Van Der Meer, Arnold; Hilbrands, Luuk B.; Baas, Marije C.; Van Reekum, Franka E.; Verhaar, Marianne C.; Kamburova, Elena G.; Seelen, Marc A. J.; Sanders, Jan Stephan; Hepkema, Bouke G.; Lambeck, Annechien J.; Bungener, Laura B.; Roozendaal, Caroline; Tilanus, Marcel G. J.; Voorter, Christien E.; Wieten, Lotte; Van Duijnhoven, Elly M.; Gelens, Mariëlle A. C. J.; Christiaans, Maarten H. L.; Van Ittersum, Frans J.; Nurmohamed, Azam; Lardy, Neubury M.; Swelsen, Wendy; Van Der Pant, Karlijn A.; Van Der Weerd, Neelke C.; Ten Berge, Ineke J. M.; Bemelman, Fréderike J.; De Vries, Aiko P. J.; De Fijter, Johan W.; Betjes, Michiel G. H.; Roelen, Dave L.; Claas, Frans H.; Otten, Henny G.; Heidt, Sebastiaan; Van Zuilen, Arjan D.; Kobayashi, Takaaki; Geneugelijk, Kirsten; Spierings, Eric
PUBLISHED IN
Frontiers in Immunology
PATIENTS
190
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.
HIGHLIGHTS
- 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.
- It is shown 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.
