Frontiers in Immunology (Mar 2018)
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 Roozendaal,
- Marcel 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,
- Michiel G. H. Betjes,
- Sebastiaan Heidt,
- Dave L. Roelen,
- Frans H. Claas,
- Henny G. Otten,
- Eric Spierings
Affiliations
- Kirsten Geneugelijk
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- Matthias Niemann
- PIRCHE AG, Berlin, Germany
- Julia Drylewicz
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- Arjan D. van Zuilen
- Department of Nephrology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- Irma Joosten
- Laboratory Medicine, Laboratory Medical Immunology, Radboud University Medical Center, Nijmegen, Netherlands
- Wil A. Allebes
- Laboratory Medicine, Laboratory Medical Immunology, Radboud University Medical Center, Nijmegen, Netherlands
- Arnold van der Meer
- Laboratory Medicine, Laboratory Medical Immunology, Radboud University Medical Center, Nijmegen, Netherlands
- Luuk B. Hilbrands
- Department of Nephrology, Radboud University Medical Center, Nijmegen, Netherlands
- Marije C. Baas
- Department of Nephrology, Radboud University Medical Center, Nijmegen, Netherlands
- C. Erik Hack
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- Franka E. van Reekum
- Department of Nephrology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- Marianne C. Verhaar
- Department of Nephrology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- Elena G. Kamburova
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- Michiel L. Bots
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- Marc A. J. Seelen
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Jan Stephan Sanders
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Bouke G. Hepkema
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Annechien J. Lambeck
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Laura B. Bungener
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Caroline Roozendaal
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Marcel G. J. Tilanus
- Department of Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, Netherlands
- Joris Vanderlocht
- 0Central Diagnostic Laboratory, Division of Immunology, Maastricht University Medical Center, Maastricht, Netherlands
- Christien E. Voorter
- Department of Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, Netherlands
- Lotte Wieten
- Department of Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, Netherlands
- Elly M. van Duijnhoven
- 1Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center, Maastricht, Netherlands
- Mariëlle Gelens
- 1Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center, Maastricht, Netherlands
- Maarten H. L. Christiaans
- 1Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center, Maastricht, Netherlands
- Frans J. van Ittersum
- 2Department of Nephrology, VU University Medical Center, Amsterdam, Netherlands
- Azam Nurmohamed
- 2Department of Nephrology, VU University Medical Center, Amsterdam, Netherlands
- Junior N. M. Lardy
- 3Department of Immunogenetics, Sanquin, Amsterdam, Netherlands
- Wendy Swelsen
- 3Department of Immunogenetics, Sanquin, Amsterdam, Netherlands
- Karlijn A. van der Pant
- 4Renal Transplant Unit, Department of Internal Medicine, Academic Medical Center (AMC), Amsterdam, Netherlands
- Neelke C. van der Weerd
- 4Renal Transplant Unit, Department of Internal Medicine, Academic Medical Center (AMC), Amsterdam, Netherlands
- Ineke J. M. ten Berge
- 4Renal Transplant Unit, Department of Internal Medicine, Academic Medical Center (AMC), Amsterdam, Netherlands
- Fréderike J. Bemelman
- 4Renal Transplant Unit, Department of Internal Medicine, Academic Medical Center (AMC), Amsterdam, Netherlands
- Andries Hoitsma
- 5Dutch Organ Transplant Registry (NOTR), Dutch Transplant Foundation (NTS), Leiden, Netherlands
- Paul J. M. van der Boog
- 6Department of Nephrology, Leiden University Medical Center, Leiden, Netherlands
- Johan W. de Fijter
- 6Department of Nephrology, Leiden University Medical Center, Leiden, Netherlands
- Michiel G. H. Betjes
- 7Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands
- Michiel G. H. Betjes
- 8Department of Nephrology, Erasmus MC, Rotterdam, Netherlands
- Sebastiaan Heidt
- 9Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
- Dave L. Roelen
- 9Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
- Frans H. Claas
- 9Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
- Henny G. Otten
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- Eric Spierings
- Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- DOI
- https://doi.org/10.3389/fimmu.2018.00321
- Journal volume & issue
-
Vol. 9
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.
Keywords