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.

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 Prague Czech Republic 10 Department of General and Transplant Surgery Innsbruck Medical University Innsbruck Austria 11 Oregon Health and Science University Portland OR

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Donor-specific antibodies require preactivated immune system to harm renal transplant