AUTHOR=Geneugelijk Kirsten , Niemann Matthias , Drylewicz Julia , van Zuilen Arjan D. , Joosten Irma , Allebes Wil A. , van der Meer Arnold , Hilbrands Luuk B. , Baas Marije C. , Hack C. Erik , van Reekum Franka E. , Verhaar Marianne C. , Kamburova Elena G. , Bots Michiel L. , Seelen Marc A. J. , Sanders Jan Stephan , Hepkema Bouke G. , Lambeck Annechien J. , Bungener Laura B. , Roozendaal Caroline , Tilanus Marcel G. J. , Vanderlocht Joris , Voorter Christien E. , Wieten Lotte , van Duijnhoven Elly M. , Gelens Mariëlle , Christiaans Maarten H. L. , van Ittersum Frans J. , Nurmohamed Azam , Lardy Junior N. M. , Swelsen Wendy , van der Pant Karlijn A. , van der Weerd Neelke C. , ten Berge Ineke J. M. , Bemelman Fréderike J. , Hoitsma Andries , van der Boog Paul J. M. , de Fijter Johan W. , Betjes Michiel G. H. , Heidt Sebastiaan , Roelen Dave L. , Claas Frans H. , Otten Henny G. , Spierings Eric TITLE=PIRCHE-II Is Related to Graft Failure after Kidney Transplantation JOURNAL=Frontiers in Immunology VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00321 DOI=10.3389/fimmu.2018.00321 ISSN=1664-3224 ABSTRACT=

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.