BACKGROUND: It is an unresolved issue why some kidney transplant recipients with pretransplant donor-specific HLA antibodies (DSA) show a high transplant failure rate, whereas in other patients DSA do not harm the graft. We investigated whether help from preactivated T-cells might be necessary for DSA to exert a deleterious effect. METHODS: The impact of pretransplant DSA and immune activation marker soluble CD30 (sCD30) on 3-year graft survival was analyzed in 385 presensitized kidney transplant recipients. FINDINGS: A deleterious influence of pretransplant DSA on graft survival was evident only in patients who were positive for the immune activation marker sCD30. In the absence of sCD30 positivity, 3-year graft survival was virtually identical in patients with or without DSA (83.1±3.9% and 84.3±2.8%, P=0.81). A strikingly lower 3-year graft survival rate of 62.1±6.4% was observed in patients who were both sCD30 and DSA positive (HR 2.92, P<0.001). Even in the presence of strong DSA with ≥5000 MFI, the 3-year graft survival rate was high if the recipients were sCD30 negative. INTERPRETATION: Pretransplant DSA have a significantly deleterious impact on graft survival only in the presence of high pretransplant levels of the activation marker sCD30.

Blood Transfusion Center University Hospitals Leuven Leuven Belgium

Department of General and Transplant Surgery Innsbruck Medical University Innsbruck Austria

Department of Immunogenetics Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Internal Medicine University Clinic of Giessen and Marburg Giessen Germany

Department of Nephrology and Renal Transplantation Leuven Belgium

Department of Transplantation Immunology Institute of Transfusion Medicine University Clinic Ulm Ulm Germany

Departments of Transfusion Medicine and Nephrology Dialysis Kidney Transplantation University Hospital Centre Rijeka Croatia

Division of Nephrology University Hospital Zurich Zurich Switzerland

Division of Nephrology University of Heidelberg Heidelberg Germany

Immunology and Histocompatibility Laboratory CHU de Québec Université Laval Québec QC Canada; Department of Microbiology Infectious Diseases and Immunology Université Laval Québec QC Canada

Oregon Health and Science University Portland OR USA

Transplantation and General Surgery University of Heidelberg Heidelberg Germany

Transplantation Immunology Institute of Immunology Heidelberg Germany

Transplantation Surgery University of Freiburg Freiburg Germany

University Medical Centre Mannheim Mannheim Germany

Welsh Transplantation and Immunogenetics Laboratory Cardiff United Kingdom

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