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Front. Immunol. | doi: 10.3389/fimmu.2018.00321

PIRCHE-II is related to graft failure after kidney transplantation

 Kirsten Geneugelijk1*,  Matthias Niemann2,  Julia Drylewicz1,  Arjan D. van Zuilen1,  Irma Joosten3, Wil A. Allebes3, Arnold van der Meer3, Luuk B. Hilbrands3,  Marije C. Baas3, C. E. Hack1, Franka E. van Reekum1,  Marianne C. Verhaar1,  Elena G. Kamburova1, Michiel L. Bots1,  Marc A. Seelen4, 5, Jan Stephan Sanders4, 5, Bouke G. Hepkema4, 5, Annechien J. Lambeck4, 5, Laura B. Bungener4, 5, Caroline Roozendaal4, 5,  Marcel G. Tilanus6,  Joris Vanderlocht6, Christien E. Voorter6, Lotte Wieten6, Elly M. van Duijnhoven6, Mariëlle Gelens6, Maarten H. Christiaans6, Frans J. van Ittersum7, Azam Nurmohamed7, Junior N. Lardy8, Wendy Swelsen8, Karlijn A. van der Pant9, Neelke C. van der Weerd9, Ineke J. ten Berge9, Fréderike J. Bemelman9, Andries Hoitsma10, Paul J. van der Boog11, Johan W. de Fijter11,  Michiel G. Betjes12,  Sebastiaan Heidt11,  Dave L. Roelen11, Frans H. Claas11,  Henny G. Otten1 and  Eric Spierings1
  • 1University Medical Center Utrecht, Netherlands
  • 2PIRCHE AG, Germany
  • 3Medical Center, Radboud University Nijmegen, Netherlands
  • 4University of Groningen, Netherlands
  • 5University Medical Center Groningen, Netherlands
  • 6Maastricht University Medical Centre, Netherlands
  • 7VU University Medical Center, Netherlands
  • 8Sanquin, Netherlands
  • 9Academic Medical Center (AMC), Netherlands
  • 10Dutch Transplant Foundation, Netherlands
  • 11Leiden University Medical Center, Netherlands
  • 12Erasmus Medical Center, Erasmus University Rotterdam, Netherlands

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 DSA 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 (HR:1.13, 95% CI:1.04-1.23, p=0.003). When analyzing a subgroup of patients who had their first transplantation, the hazard ratio of graft failure for ln(PIRCHE-II) was higher compared to 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.

Keywords: PIRCHE-II, Kidney Transplantation, Graft Rejection, HLA Antigens, HLA matching

Received: 10 Aug 2017; Accepted: 05 Feb 2018.

Edited by:

Aurore Saudemont, GlaxoSmithKline (United Kingdom), United Kingdom

Reviewed by:

Hans-Dieter Volk, Berlin-Brandenburg Center for Regenerative Therapies, Charité - University Medicine, Germany
Yuqun Zeng, Zhejiang Provincial People's Hospital, China  

Copyright: © 2018 Geneugelijk, Niemann, Drylewicz, van Zuilen, Joosten, Allebes, van der Meer, Hilbrands, Baas, Hack, van Reekum, Verhaar, Kamburova, Bots, Seelen, Sanders, Hepkema, Lambeck, Bungener, Roozendaal, Tilanus, Vanderlocht, Voorter, Wieten, van Duijnhoven, Gelens, Christiaans, van Ittersum, Nurmohamed, Lardy, Swelsen, van der Pant, van der Weerd, ten Berge, Bemelman, Hoitsma, van der Boog, de Fijter, Betjes, Heidt, Roelen, Claas, Otten and Spierings. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Kirsten Geneugelijk, University Medical Center Utrecht, Utrecht, Netherlands, C.C.A.Geneugelijk-2@umcutrecht.nl