Peripheral B-Cell Phenotype and BAFF Levels are Associated With HLA Immunization in Patients Awaiting Kidney Transplantation

Background The role of B-cell subsets in human leukocyte antigen (HLA)-specific humoral responses in patients with end-stage renal disease is poorly documented. The objective of this study was to analyze the potential association between B-cell subsets distribution and anti-HLA antibodies before kidney transplantation. Methods The authors studied by flow cytometry peripheral B-cell subsets and serum levels of BAFF, the main homeostatic cytokine for peripheral B cells, in 101 consecutive end-stage renal disease patients admitted for transplantation. Results In patients with HLA antibodies detected with Luminex single antigen, the proportion of activated naive B cells (Bm2) was significantly higher (64.415.1% vs. 52.5 +/- 19.1% in HLA antibody-negative patients, P=0.0008) at the expense of memory B cells, as were BAFF serum levels (1,651 +/- 1,297 vs. 1,139 +/- 693 pg/mL, P<0.0001). Proportion of Bm2 and BAFF levels were positively associated with the diversity of anti-HLA antibodies. In multivariate analysis, besides HLA-immunizing events (pregnancy and previous transplantation), proportion of Bm2 cells but not of other B-cell subsets or BAFF levels was independently associated with the presence and diversity of anti-HLA antibodies. High proportion of Bm2 cells before transplantation was associated with an increased risk of developing de novo donor-specific antibodies during the first year posttransplant. The authors did not find any association between the frequency of antibody-mediated rejection and pretransplant proportion of any B-cell subset or BAFF serum levels. Conclusion Increased proportions of activated naive B cells are linked with pretransplant HLA immunization and the development of posttransplant donor-specific antibodies.