PIRCHE-II is related to graft failure after kidney transplantation

Kirsten Geneugelijk, Matthias Niemann, Julia Drylewicz, Arjan D. van Zuilen, Irma Joosten, Wil A. Allebes, Arnold van der Meer, Luuk B. Hilbrands, Marije C. Baas, C. Erik Hack, Franka E. van Reekum, Marianne C. Verhaar, Elena G. Kamburova, Michiel L. Bots, Marc A. J. Seelen, Jan Stephan Sanders, Bouke G. Hepkema, Annechien J. Lambeck, Laura B. Bungener, Caroline RoozendaalMarcel G. J. Tilanus, Joris Vanderlocht, Christien E. Voorter, Lotte Wieten, Elly M. van Duijnhoven, Mariëlle Gelens, Maarten H. L. Christiaans, Frans J. van Ittersum, Azam Nurmohamed, Junior N. M. Lardy, Wendy Swelsen, Karlijn A. van der Pant, Neelke C. van der Weerd, Ineke J. M. ten Berge, Fréderike J. Bemelman, Andries Hoitsma, Paul J. M. van der Boog, Johan W. de Fijter, Michiel G. H. Betjes, Sebastiaan Heidt, Dave L. Roelen, Frans H. Claas, Henny G. Otten, Eric Spierings

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Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in de novo donor-specific HLA antibodies formation after kidney transplantation. In the present Dutch multi-center study, we evaluated the possible association between PIRCHE-II and kidney graft failure in 2,918 donor-recipient couples that were transplanted between 1995 and 2005. For these donors-recipients couples, PIRCHE-II numbers were related to graft survival in univariate and multivariable analyses. Adjusted for confounders, the natural logarithm of PIRCHE-II was associated with a higher risk for graft failure [hazard ratio (HR): 1.13, 95% CI: 1.04-1.23, p = 0.003]. When analyzing a subgroup of patients who had their first transplantation, the HR of graft failure for ln(PIRCHE-II) was higher compared with the overall cohort (HR: 1.22, 95% CI: 1.10-1.34, p < 0.001). PIRCHE-II demonstrated both early and late effects on graft failure in this subgroup. These data suggest that the PIRCHE-II may impact graft survival after kidney transplantation. Inclusion of PIRCHE-II in donor-selection criteria may eventually lead to an improved kidney graft survival.
Original languageEnglish
Article number321
JournalFrontiers in Immunology
Issue numberMAR
Publication statusPublished - 2018

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