Frontiers in Immunology (Sep 2022)

The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation – Data from the Swiss transplant cohort study

  • Lukas Frischknecht,
  • Yun Deng,
  • Caroline Wehmeier,
  • Olivier de Rougemont,
  • Jean Villard,
  • Sylvie Ferrari-Lacraz,
  • Déla Golshayan,
  • Monique Gannagé,
  • Isabelle Binet,
  • Urs Wirthmueller,
  • Daniel Sidler,
  • Thomas Schachtner,
  • Stefan Schaub,
  • Jakob Nilsson,
  • the Swiss Transplant Cohort Study,
  • Patrizia Amico,
  • Andres Axel,
  • John David Aubert,
  • Vanessa Banz,
  • Beckmann Sonja,
  • Guido Beldi,
  • Christoph Berger,
  • Ekaterine Berishvili,
  • Isabelle Binet,
  • Pierre-Yves Bochud,
  • Sanda Branca,
  • Heiner Bucher,
  • Thierry Carrel,
  • Emmanuelle Catana,
  • Yves Chalandon,
  • Sabina De Geest,
  • Olivier De Rougemont,
  • Michael Dickenmann,
  • Joëlle Lynn Dreifuss,
  • Michel Duchosal,
  • Thomas Fehr,
  • Sylvie Ferrari-Lacraz,
  • Nicola Franscini,
  • Christian Garzoni,
  • Paola Gasche Soccal,
  • Christophe Gaudet,
  • Déla Golshayan,
  • Nicolas Goossens,
  • Karine Hadaya,
  • Jörg Halter,
  • Dominik Heim,
  • Christoph Hess,
  • Sven Hillinger,
  • Hans Hirsch,
  • Patricia Hirt,
  • Günther Hofbauer,
  • Uyen Huynh-Do,
  • Franz Immer,
  • Michael Koller (Head of the data center),
  • Mirjam. Laager,
  • Bettina Laesser,
  • Roger Lehmann,
  • Alexander Leichtle,
  • Christian Lovis,
  • Oriol Manuel,
  • Hans-Peter Marti,
  • Pierre Yves Martin,
  • Michele Martinelli,
  • Valérie McLin,
  • Katell Mellac,
  • Aurelia Mercay,
  • Karin Mettler,
  • Nicolas Mueller (Chairman Scientific Committee),
  • Antonia Müller,
  • Thomas Müller,
  • Ulrike Müller-Arndt,
  • Beat Müllhaupt,
  • Mirjam Nägeli,
  • Graziano Oldani,
  • Manuel Pascual (Executive office),
  • Klara Posfay-Barbe,
  • Juliane Rick,
  • Anne Rosselet,
  • Simona Rossi,
  • Silvia Rothlin,
  • Frank Ruschitzka,
  • Urs Schanz,
  • Stefan Schaub,
  • Aurelia Schnyder,
  • Macé Schuurmans,
  • Thierry Sengstag,
  • Federico Simonetta,
  • Katharina Staufer,
  • Susanne Stampf,
  • Jürg Steiger (Head,
  • Excecutive office),
  • Guido Stirniman,
  • Ueli Stürzinger,
  • Christian Van Delden (Executive office),
  • Jean-Pierre Venetz,
  • Jean Villard,
  • Julien Vionnet,Madeleine Wick (STCS coordinator),
  • Markus Wilhlem,
  • Patrick Yerly

DOI
https://doi.org/10.3389/fimmu.2022.1005790
Journal volume & issue
Vol. 13

Abstract

Read online

BackgroundPre-transplant donor specific antibodies (DSA), directed at non-self human leukocyte antigen (HLA) protein variants present in the donor organ, have been associated with worse outcomes in kidney transplantation. The impact of the mean fluorescence intensity (MFI) and the target HLA antigen of the detected DSA has, however, not been conclusively studied in a large cohort with a complete virtual cross-match (vXM).MethodsWe investigated the effect of pre-transplant DSA on the risk of antibody-mediated rejection (ABMR), graft loss, and the rate of eGFR decline in 411 DSA positive transplants and 1804 DSA negative controls.ResultsPre-transplant DSA were associated with a significantly increased risk of ABMR, graft loss, and accelerated eGFR decline. DSA directed at Class I and Class II HLA antigens were strongly associated with increased risk of ABMR, but only DSA directed at Class II associated with graft loss. DSA MFI markedly affected outcome, and Class II DSA were associated with ABMR already at 500-1000 MFI, whereas Class I DSA did not affect outcome at similar low MFI values. Furthermore, isolated DSA against HLA-DP carried comparable risks for ABMR, accelerated eGFR decline, and graft loss as DSA against HLA-DR.ConclusionOur results have important implications for the construction and optimization of vXM algorithms used within organ allocation systems. Our data suggest that both the HLA antigen target of the detected DSA as well as the cumulative MFI should be considered and that different MFI cut-offs could be considered for Class I and Class II directed DSA.

Keywords