Purpose. Our objective was to provide the first precise study of peripheral B cell phenotype and BAFF serum level in relation with pre-transplant HLA immunization. Methods. In 101 unselected kidney transplant recipients admitted for transplantation, before any treatment, phenotyping of lymphocyte subsets was performed on freshly drawn blood using the Bm classification (CD19, IgD, CD38 staining). Patients were considered immunized if they displayed HLA antibodies at day-0 with Luminex single antigen with a cut-off value of MFI at 3000. Diversity of HLA immunization was assessed as the number of positive single antigen flow beads. BAFF serum levels were measured by ELISA. Results. In the whole population, 49.5% of patients displayed HLA antibodies. Bm2 activated naÏve B cells accounted for 58.4±18.2% of B cells – representing the main circulating subset – and Bm5 memory cells 24.4±14.5%. In immunized patients, the percentage of Bm2 cells at day-0 was significantly higher (64.4±15.1% versus 52.5±19.1% in other patients, p=0.0008) at the expense of virgin naÏve (Bm1) and memory B cells (Bm5). Percentages of transitional cells and plasmablasts were similar. BAFF serum levels were higher in patients carrying HLA antibodies: 1651±1297 versus 1139±693 pg/mL, p<0.0001. Regarding the diversity of HLA immunization, BAFF serum concentration increased together with the number of reactive positive beads (distributed in quartiles).

No difference was observed in the repartition of day-0 B-cell subsets and in day-0 BAFF serum levels among patients who experienced antibody-mediated rejection or occurrence of de novo donor-specific antibodies during the first year post-transplant.

Conclusion. Pre-transplant HLA immunization is associated with an activated B cell phenotype and increase in BAFF serum level. Moreover BAFF correlates with diversity of HLA immunization, suggesting a role for BAFF in HLA-specific humoral responses before transplantation.

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