Caner Süsal1, Daniel Wettstein, Bernd Döhler, Christian Morath, Andrea Ruhenstroth, Sabine Scherer, Thuong H Tran, Petra Gombos, Peter Schemmer, Eric Wagner, Thomas Fehr, Stela Živčić-Ćosić, Sanja Balen, Rolf Weimer, Antonij Slavcev, Claudia Bösmüller, Douglas J Norman, Martin Zeier, Gerhard Opelz. 1. 1 Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany. 2 Department of Nephrology, University of Heidelberg, Heidelberg, Germany. 3 Department of Transplantation and General Surgery, University of Heidelberg, Heidelberg, Germany. 4 Immunology and Histocompatibility Laboratory, CHU de Quebec, Quebec, QC, Canada. 5 Department of Microbiology, Infectious Diseases and Immunology, Laval University, Quebec, QC, Canada. 6 Division of Nephrology, University Hospital Zurich, Switzerland. 7 Departments of Nephrology, Dialysis, Kidney Transplantation and Transfusion Medicine, University Hospital Centre, Rijeka, Croatia. 8 Department of Internal Medicine, University Clinic of Giessen and Marburg, Campus Giessen, Giessen, Germany. 9 Department of Immunogenetics, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic. 10 Department of General and Transplant Surgery, Innsbruck Medical University, Innsbruck, Austria. 11 Oregon Health and Science University, Portland, OR.
Abstract
BACKGROUND: The association of donor-specific HLA antibodies (DSA) with kidney graft failure has been addressed previously; however, the majority of studies were based on small numbers of patients with graft failure. METHODS: We investigated 83 patients with failed kidney transplants for a possible association of de novo development and persistence or loss of pre-existing DSA with graft failure. Single Antigen Bead assay-detected DSA and non-DSA antibodies were compared between patients with graft loss and matched controls with functioning grafts. RESULTS: The incidence of weak de novo DSA or non-DSA at a mean fluorescence intensity of 500 or higher was higher in the graft loss than in the nonrejector group (76% vs 40%, P < 0.001). Because of the low number of patients developing de novo DSA, the DSA results did not reach statistical significance (only 22% of patients with graft loss developed de novo DSA). However, at all cutoffs, there was a significantly higher rate of graft loss in patients with de novo non-DSA. The incidence of strong pretransplant DSA that persist after transplantation was higher in the graft loss group (10% vs 1%, P = 0.034). When C1q-binding ability in sera of rejectors and nonrejectors with posttransplant de novo or persistent DSA was compared, none of the nonrejectors demonstrated C1q positivity, whereas 43% of patients with graft loss showed C1q-positive antibodies, although not necessarily donor-specific (P < 0.001). CONCLUSIONS: Our data show that the posttransplant presence of persisting or de novo HLA antibodies, especially if C1q binding, is associated with graft loss, even if the antibodies are not specific for mismatched donor HLA.
BACKGROUND: The association of donor-specific HLA antibodies (DSA) with kidney graft failure has been addressed previously; however, the majority of studies were based on small numbers of patients with graft failure. METHODS: We investigated 83 patients with failed kidney transplants for a possible association of de novo development and persistence or loss of pre-existing DSA with graft failure. Single Antigen Bead assay-detected DSA and non-DSA antibodies were compared between patients with graft loss and matched controls with functioning grafts. RESULTS: The incidence of weak de novo DSA or non-DSA at a mean fluorescence intensity of 500 or higher was higher in the graft loss than in the nonrejector group (76% vs 40%, P < 0.001). Because of the low number of patients developing de novo DSA, the DSA results did not reach statistical significance (only 22% of patients with graft loss developed de novo DSA). However, at all cutoffs, there was a significantly higher rate of graft loss in patients with de novo non-DSA. The incidence of strong pretransplant DSA that persist after transplantation was higher in the graft loss group (10% vs 1%, P = 0.034). When C1q-binding ability in sera of rejectors and nonrejectors with posttransplant de novo or persistent DSA was compared, none of the nonrejectors demonstrated C1q positivity, whereas 43% of patients with graft loss showed C1q-positive antibodies, although not necessarily donor-specific (P < 0.001). CONCLUSIONS: Our data show that the posttransplant presence of persisting or de novo HLA antibodies, especially if C1q binding, is associated with graft loss, even if the antibodies are not specific for mismatched donor HLA.
Authors: Sarah B See; Benjamin S Mantell; Kevin J Clerkin; Bryan Ray; E Rodica Vasilescu; Charles C Marboe; Yoshifumi Naka; Susan Restaino; Paolo C Colombo; Linda J Addonizio; Maryjane A Farr; Emmanuel Zorn Journal: Am J Transplant Date: 2020-04-26 Impact factor: 8.086