T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation

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 H...

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Autores principales:	Emma T. M. Peereboom, Benedict M. Matern, Toshihide Tomosugi, Matthias Niemann, Julia Drylewicz, Irma Joosten, Wil A. Allebes, Arnold van der Meer, Luuk B. Hilbrands, Marije C. Baas, Franka E. van Reekum, Marianne C. Verhaar, Elena G. Kamburova, Marc A. J. Seelen, Jan Stephan Sanders, Bouke G. Hepkema, Annechien J. Lambeck, Laura B. Bungener, Caroline Roozendaal, Marcel G. J. Tilanus, Christien E. Voorter, Lotte Wieten, Elly M. van Duijnhoven, Mariëlle A. C. J. Gelens, Maarten H. L. Christiaans, Frans J. van Ittersum, Azam Nurmohamed, Neubury M. Lardy, Wendy Swelsen, Karlijn A. van der Pant, Neelke C. van der Weerd, Ineke J. M. ten Berge, Fréderike J. Bemelman, Aiko P. J. de Vries, Johan W. de Fijter, Michiel G. H. Betjes, Dave L. Roelen, Frans H. Claas, Henny G. Otten, Sebastiaan Heidt, Arjan D. van Zuilen, Takaaki Kobayashi, Kirsten Geneugelijk, Eric Spierings
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	HLA antigens PIRCHE-II graft failure kidney transplantation shared T-cell epitopes T-cell epitope Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/304c2f59ef3743a597b164b0c8125533
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spelling	oai:doaj.org-article:304c2f59ef3743a597b164b0c81255332021-11-18T08:34:01ZT-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation1664-322410.3389/fimmu.2021.784040https://doaj.org/article/304c2f59ef3743a597b164b0c81255332021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.784040/fullhttps://doaj.org/toc/1664-3224CD4+ 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.Emma T. M. PeereboomBenedict M. MaternToshihide TomosugiToshihide TomosugiMatthias NiemannJulia DrylewiczIrma JoostenWil A. AllebesArnold van der MeerLuuk B. HilbrandsMarije C. BaasFranka E. van ReekumMarianne C. VerhaarElena G. KamburovaMarc A. J. SeelenJan Stephan SandersBouke G. HepkemaAnnechien J. LambeckLaura B. BungenerCaroline RoozendaalMarcel G. J. TilanusChristien E. VoorterLotte WietenElly M. van DuijnhovenMariëlle A. C. J. GelensMaarten H. L. ChristiaansFrans J. van IttersumAzam NurmohamedNeubury M. LardyWendy SwelsenKarlijn A. van der PantNeelke C. van der WeerdIneke J. M. ten BergeFréderike J. BemelmanAiko P. J. de VriesJohan W. de FijterMichiel G. H. BetjesMichiel G. H. BetjesDave L. RoelenFrans H. ClaasHenny G. OttenSebastiaan HeidtArjan D. van ZuilenTakaaki KobayashiKirsten GeneugelijkEric SpieringsFrontiers Media S.A.articleHLA antigensPIRCHE-IIgraft failurekidney transplantationshared T-cell epitopesT-cell epitopeImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HLA antigens PIRCHE-II graft failure kidney transplantation shared T-cell epitopes T-cell epitope Immunologic diseases. Allergy RC581-607
spellingShingle	HLA antigens PIRCHE-II graft failure kidney transplantation shared T-cell epitopes T-cell epitope Immunologic diseases. Allergy RC581-607 Emma T. M. Peereboom Benedict M. Matern Toshihide Tomosugi Toshihide Tomosugi Matthias Niemann Julia Drylewicz Irma Joosten Wil A. Allebes Arnold van der Meer Luuk B. Hilbrands Marije C. Baas Franka E. van Reekum Marianne C. Verhaar Elena G. Kamburova Marc A. J. Seelen Jan Stephan Sanders Bouke G. Hepkema Annechien J. Lambeck Laura B. Bungener Caroline Roozendaal Marcel G. J. Tilanus Christien E. Voorter Lotte Wieten Elly M. van Duijnhoven Mariëlle A. C. J. Gelens Maarten H. L. Christiaans Frans J. van Ittersum Azam Nurmohamed Neubury M. Lardy Wendy Swelsen Karlijn A. van der Pant Neelke C. van der Weerd Ineke J. M. ten Berge Fréderike J. Bemelman Aiko P. J. de Vries Johan W. de Fijter Michiel G. H. Betjes Michiel G. H. Betjes Dave L. Roelen Frans H. Claas Henny G. Otten Sebastiaan Heidt Arjan D. van Zuilen Takaaki Kobayashi Kirsten Geneugelijk Eric Spierings T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation
description	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.
format	article
author	Emma T. M. Peereboom Benedict M. Matern Toshihide Tomosugi Toshihide Tomosugi Matthias Niemann Julia Drylewicz Irma Joosten Wil A. Allebes Arnold van der Meer Luuk B. Hilbrands Marije C. Baas Franka E. van Reekum Marianne C. Verhaar Elena G. Kamburova Marc A. J. Seelen Jan Stephan Sanders Bouke G. Hepkema Annechien J. Lambeck Laura B. Bungener Caroline Roozendaal Marcel G. J. Tilanus Christien E. Voorter Lotte Wieten Elly M. van Duijnhoven Mariëlle A. C. J. Gelens Maarten H. L. Christiaans Frans J. van Ittersum Azam Nurmohamed Neubury M. Lardy Wendy Swelsen Karlijn A. van der Pant Neelke C. van der Weerd Ineke J. M. ten Berge Fréderike J. Bemelman Aiko P. J. de Vries Johan W. de Fijter Michiel G. H. Betjes Michiel G. H. Betjes Dave L. Roelen Frans H. Claas Henny G. Otten Sebastiaan Heidt Arjan D. van Zuilen Takaaki Kobayashi Kirsten Geneugelijk Eric Spierings
author_facet	Emma T. M. Peereboom Benedict M. Matern Toshihide Tomosugi Toshihide Tomosugi Matthias Niemann Julia Drylewicz Irma Joosten Wil A. Allebes Arnold van der Meer Luuk B. Hilbrands Marije C. Baas Franka E. van Reekum Marianne C. Verhaar Elena G. Kamburova Marc A. J. Seelen Jan Stephan Sanders Bouke G. Hepkema Annechien J. Lambeck Laura B. Bungener Caroline Roozendaal Marcel G. J. Tilanus Christien E. Voorter Lotte Wieten Elly M. van Duijnhoven Mariëlle A. C. J. Gelens Maarten H. L. Christiaans Frans J. van Ittersum Azam Nurmohamed Neubury M. Lardy Wendy Swelsen Karlijn A. van der Pant Neelke C. van der Weerd Ineke J. M. ten Berge Fréderike J. Bemelman Aiko P. J. de Vries Johan W. de Fijter Michiel G. H. Betjes Michiel G. H. Betjes Dave L. Roelen Frans H. Claas Henny G. Otten Sebastiaan Heidt Arjan D. van Zuilen Takaaki Kobayashi Kirsten Geneugelijk Eric Spierings
author_sort	Emma T. M. Peereboom
title	T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation
title_short	T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation
title_full	T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation
title_fullStr	T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation
title_full_unstemmed	T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation
title_sort	t-cell epitopes shared between immunizing hla and donor hla associate with graft failure after kidney transplantation
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/304c2f59ef3743a597b164b0c8125533
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T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation

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