Pretransplant serum BAFF levels are associated with pretransplant HLA immunization and renal allograft survival

Background: The essential function of B cell-activating factor (BAFF) is regulating the survival and differentiation of B cells. The link between pretransplant BAFF levels and pretransplant alloimmunization and its value to predict subsequent acute antibody-mediated rejection (AMR) and outcome after renal transplantation is not fully understood. Methods: Objective of our retrospective single-center study was to determine, by ELISA analysis of pretransplant serum BAFF levels in 249 patients undergoing renal transplantation, association between preformed anti-human leukocyte antigen (HLA) antibodies, occurrence of acute antibody mediated rejection (AMR) and renal allograft survival. Results: Pretransplant serum BAFF levels were significantly higher in presensitized recipients with anti-HLA antibodies (3262 +/- 2796 pg/ml) than in recipients without occurrence of anti-HLA antibodies (2252 +/- 1425 pg/ml; p < 0.0001). In addition, pretransplant BAFF levels correlated with cumulative MFI values of anti-HLA antibodies (r = 0.2966, p = 0.0025). Patients with high pretransplant BAFF levels ( >= 2137 pg/ml) experienced significantly lower allograft survival rates compared to low pretransplant BAFF levels (80% vs. 91%; p = 0.01). Coexistence of high pretransplant BAFF levels and posttransplant AMR was associated with the worst allograft survival rates (56%). Relative risk (RR) for allograft loss was associated with high serum BAFF levels (RR 2.3; p = 0.02), presence of anti-HLA antibodies (RR 2.5; p = 0.007) or anti-HLA -donor-specific antibodies (DSAs) (RR 2.6; p = 0.003) before transplant and AMR post transplant (RR 2.5; p = 0.007). AMR was the strongest independent risk factor for allograft failure (RR 2.6; p = 0.03). Conclusion: Elevated pretransplant serum BAFF levels negatively affect renal allograft survival and represent a risk factor for allosensitization and subsequent AMR.