PMID- 36211367 OWN - NLM STAT- MEDLINE DCOM- 20221011 LR - 20221012 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation - Data from the Swiss transplant cohort study. PG - 1005790 LID - 10.3389/fimmu.2022.1005790 [doi] LID - 1005790 AB - 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. CI - Copyright (c) 2022 Frischknecht, Deng, Wehmeier, de Rougemont, Villard, Ferrari-Lacraz, Golshayan, Gannage, Binet, Wirthmueller, Sidler, Schachtner, Schaub, Nilsson and the Swiss Transplant Cohort Study. FAU - Frischknecht, Lukas AU - Frischknecht L AD - Department of Immunology, University Hospital Zurich (USZ), Zurich, Switzerland. FAU - Deng, Yun AU - Deng Y AD - Department of Immunology, University Hospital Zurich (USZ), Zurich, Switzerland. FAU - Wehmeier, Caroline AU - Wehmeier C AD - Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland. FAU - de Rougemont, Olivier AU - de Rougemont O AD - Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland. FAU - Villard, Jean AU - Villard J AD - Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland. FAU - Ferrari-Lacraz, Sylvie AU - Ferrari-Lacraz S AD - Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland. FAU - Golshayan, Dela AU - Golshayan D AD - Transplantation Center, Lausanne University Hospital, Lausanne, Switzerland. FAU - Gannage, Monique AU - Gannage M AD - Service of Immunology and Allergy, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland. FAU - Binet, Isabelle AU - Binet I AD - Nephrology & Transplantation Medicine, Cantonal Hospital St. Gallen, St. Gallen, Switzerland. FAU - Wirthmueller, Urs AU - Wirthmueller U AD - Department of Laboratory Medicine, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland. FAU - Sidler, Daniel AU - Sidler D AD - Department of Nephrology and Hypertension, Inselspital, Berne University Hospital and University of Berne, Berne, Switzerland. FAU - Schachtner, Thomas AU - Schachtner T AD - Division of Nephrology, University Hospital Zurich, Zurich, Switzerland. FAU - Schaub, Stefan AU - Schaub S AD - Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland. FAU - Nilsson, Jakob AU - Nilsson J AD - Department of Immunology, University Hospital Zurich (USZ), Zurich, Switzerland. CN - Swiss Transplant Cohort Study LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220921 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Antibodies) RN - 0 (HLA Antigens) RN - 0 (HLA-DP Antigens) SB - IM MH - Antibodies MH - Cohort Studies MH - Graft Rejection MH - Graft Survival MH - HLA Antigens MH - HLA-DP Antigens MH - Humans MH - *Kidney Transplantation/adverse effects MH - Switzerland MH - Tissue Donors PMC - PMC9532952 OTO - NOTNLM OT - abmr OT - donor specific antibodies OT - graft loss OT - kidney transplantation OT - virtual cross-match COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. FIR - Amico, Patrizia IR - Amico P FIR - Axel, Andres IR - Axel A FIR - Aubert, John David IR - Aubert JD FIR - Banz, Vanessa IR - Banz V FIR - Sonja, Beckmann IR - Sonja B FIR - Beldi, Guido IR - Beldi G FIR - Berger, Christoph IR - Berger C FIR - Berishvili, Ekaterine IR - Berishvili E FIR - Binet, Isabelle IR - Binet I FIR - Bochud, Pierre-Yves IR - Bochud PY FIR - Branca, Sanda IR - Branca S FIR - Bucher, Heiner IR - Bucher H FIR - Carrel, Thierry IR - Carrel T FIR - Catana, Emmanuelle IR - Catana E FIR - Chalandon, Yves IR - Chalandon Y FIR - Geest, Sabina De IR - Geest S FIR - Rougemont, Olivier De IR - Rougemont O FIR - Dickenmann, Michael IR - Dickenmann M FIR - Dreifuss, Joelle Lynn IR - Dreifuss JL FIR - Duchosal, Michel IR - Duchosal M FIR - Fehr, Thomas IR - Fehr T FIR - Ferrari-Lacraz, Sylvie IR - Ferrari-Lacraz S FIR - Franscini, Nicola IR - Franscini N FIR - Garzoni, Christian IR - Garzoni C FIR - Soccal, Paola Gasche IR - Soccal PG FIR - Gaudet, Christophe IR - Gaudet C FIR - Golshayan, Dela IR - Golshayan D FIR - Goossens, Nicolas IR - Goossens N FIR - Hadaya, Karine IR - Hadaya K FIR - Halter, Jorg IR - Halter J FIR - Heim, Dominik IR - Heim D FIR - Hess, Christoph IR - Hess C FIR - Hillinger, Sven IR - Hillinger S FIR - Hirsch, Hans IR - Hirsch H FIR - Hirt, Patricia IR - Hirt P FIR - Hofbauer, Gunther IR - Hofbauer G FIR - Huynh-Do, Uyen IR - Huynh-Do U FIR - Immer, Franz IR - Immer F FIR - Center, Michael Koller Head Of The Data IR - Center MKHOTD FIR - Laager, Mirjam IR - Laager M FIR - Laesser, Bettina IR - Laesser B FIR - Lehmann, Roger IR - Lehmann R FIR - Leichtle, Alexander IR - Leichtle A FIR - Lovis, Christian IR - Lovis C FIR - Manuel, Oriol IR - Manuel O FIR - Marti, Hans-Peter IR - Marti HP FIR - Martin, Pierre Yves IR - Martin PY FIR - Martinelli, Michele IR - Martinelli M FIR - McLin, Valerie IR - McLin V FIR - Mellac, Katell IR - Mellac K FIR - Mercay, Aurelia IR - Mercay A FIR - Mettler, Karin IR - Mettler K FIR - Committee, Nicolas Mueller Chairman Scientific IR - Committee NMCS FIR - Muller, Antonia IR - Muller A FIR - Muller, Thomas IR - Muller T FIR - Muller-Arndt, Ulrike IR - Muller-Arndt U FIR - Mullhaupt, Beat IR - Mullhaupt B FIR - Nageli, Mirjam IR - Nageli M FIR - Oldani, Graziano IR - Oldani G FIR - Office, Manuel Pascual Executive IR - Office MPE FIR - Posfay-Barbe, Klara IR - Posfay-Barbe K FIR - Rick, Juliane IR - Rick J FIR - Rosselet, Anne IR - Rosselet A FIR - Rossi, Simona IR - Rossi S FIR - Rothlin, Silvia IR - Rothlin S FIR - Ruschitzka, Frank IR - Ruschitzka F FIR - Schanz, Urs IR - Schanz U FIR - Schaub, Stefan IR - Schaub S FIR - Schnyder, Aurelia IR - Schnyder A FIR - Schuurmans, Mace IR - Schuurmans M FIR - Sengstag, Thierry IR - Sengstag T FIR - Simonetta, Federico IR - Simonetta F FIR - Staufer, Katharina IR - Staufer K FIR - Stampf, Susanne IR - Stampf S FIR - Head, Jurg Steiger IR - Head JS FIR - Office, Excecutive IR - Office E FIR - Stirniman, Guido IR - Stirniman G FIR - Sturzinger, Ueli IR - Sturzinger U FIR - Office, Christian Van Delden Executive IR - Office CVDE FIR - Venetz, Jean-Pierre IR - Venetz JP FIR - Villard, Jean IR - Villard J FIR - Coordinator, Julien Vionnet Madeleine Wick Stcs IR - Coordinator JVMWS FIR - Wilhlem, Markus IR - Wilhlem M FIR - Yerly, Patrick IR - Yerly P EDAT- 2022/10/11 06:00 MHDA- 2022/10/12 06:00 PMCR- 2022/01/01 CRDT- 2022/10/10 03:53 PHST- 2022/07/28 00:00 [received] PHST- 2022/09/05 00:00 [accepted] PHST- 2022/10/10 03:53 [entrez] PHST- 2022/10/11 06:00 [pubmed] PHST- 2022/10/12 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.1005790 [doi] PST - epublish SO - Front Immunol. 2022 Sep 21;13:1005790. doi: 10.3389/fimmu.2022.1005790. eCollection 2022.