AUTHOR=Frischknecht Lukas , Deng Yun , Wehmeier Caroline , de Rougemont Olivier , Villard Jean , Ferrari-Lacraz Sylvie , Golshayan Déla , Gannagé Monique , Binet Isabelle , Wirthmueller Urs , Sidler Daniel , Schachtner Thomas , Schaub Stefan , Nilsson Jakob , the Swiss Transplant Cohort Study , Amico Patrizia , Axel Andres , Aubert John David , Banz Vanessa , Sonja Beckmann , Beldi Guido , Berger Christoph , Berishvili Ekaterine , Binet Isabelle , Bochud Pierre-Yves , Branca Sanda , Bucher Heiner , Carrel Thierry , Catana Emmanuelle , Chalandon Yves , Geest Sabina De , Rougemont Olivier De , Dickenmann Michael , Dreifuss Joëlle Lynn , Duchosal Michel , Fehr Thomas , Ferrari-Lacraz Sylvie , Franscini Nicola , Garzoni Christian , Soccal Paola Gasche , Gaudet Christophe , Golshayan Déla , Goossens Nicolas , Hadaya Karine , Halter Jörg , Heim Dominik , Hess Christoph , Hillinger Sven , Hirsch Hans , Hirt Patricia , Hofbauer Günther , Huynh-Do Uyen , Immer Franz , center) Michael Koller (Head of the data , Laager Mirjam. , Laesser Bettina , Lehmann Roger , Leichtle Alexander , Lovis Christian , Manuel Oriol , Marti Hans-Peter , Martin Pierre Yves , Martinelli Michele , McLin Valérie , Mellac Katell , Mercay Aurelia , Mettler Karin , Committee) Nicolas Mueller (Chairman Scientific , Müller Antonia , Müller Thomas , Müller-Arndt Ulrike , Müllhaupt Beat , Nägeli Mirjam , Oldani Graziano , office) Manuel Pascual (Executive , Posfay-Barbe Klara , Rick Juliane , Rosselet Anne , Rossi Simona , Rothlin Silvia , Ruschitzka Frank , Schanz Urs , Schaub Stefan , Schnyder Aurelia , Schuurmans Macé , Sengstag Thierry , Simonetta Federico , Staufer Katharina , Stampf Susanne , (Head Jürg Steiger , office) Excecutive , Stirniman Guido , Stürzinger Ueli , office) Christian Van Delden (Executive , Venetz Jean-Pierre , Villard Jean , coordinator) Julien Vionnet,Madeleine Wick (STCS , Wilhlem Markus , Yerly Patrick TITLE=The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation – Data from the Swiss transplant cohort study JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1005790 DOI=10.3389/fimmu.2022.1005790 ISSN=1664-3224 ABSTRACT=Background

Pre-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).

Methods

We 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.

Results

Pre-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.

Conclusion

Our 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.