In vivo human B-cell subset recovery after in vivo depletion with rituximab,anti-human CD20 monoclonal antibody

Abstract

Rituximab, chimeric anti-human CD20 monoclonal antibody approved for B-cell lymphoma, depletes circulating B cells. Little data exist on its use for nonmalignant diseases or B-cell subset recovery after treatment. We hypothesized that rituximab may reduce panel reactive alloantibodies (PRA) in dialysis patients awaiting renal transplantation and performed a single-dose, dose-escalation phase 1 trial. Here we report changes in lymphocyte phenotypes in subjects treated with rituximab alone. Nine subjects, 44 ± 10 years(Yr); (5 F, 4 M) received one dose (n=3) at 50, 150, or 375 mg/m² without other immunosuppression. Blood was collected before dosing and intervals thereafter. No significant changes in leukocytes, total or CD3⁺ lymphocytes were noted. In all, there was CD19⁺ depletion by day 2(D2) (12.0 ± 5.6 cells/mm³ vs. 181 ± 137, D0; p<0.01) and CD20⁺ (11.0 ± 12.0 vs. 205 ± 116, D0; p<0.01). At 6 months (mo), CD19⁺ and CD20⁺ remained low (51.1 ± 42.2, p<0.05; 75.4 ± 38.7, p<0.05, respectively) compared to D0. CD19⁺CD5⁺ cells recovered more rapidly, returning to baseline by 6mo while B memory cells (CD19⁺CD27⁺) remained low (32.3 ± 29.0) at 1Yr (7.5 ± 4.5; p<0.001) and 2Yr (12.1 ± 7.9; p<0.001) after treatment. We conclude that single dose rituximab ablates B cells in high PRA dialysis patients awaiting transplantation. B-cell ablation, particularly memory B cells, was long-lasting, lagging repopulation by CD5⁺ B cells.