Affiliations: [a] Indiana University School of Medicine, Department of Surgery, Indianapolis, IN, USA | [b] Indiana University School of Medicine, Department of Microbiology/Immunology, Indianapolis, IN, USA
Correspondence:
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Corresponding author: Indiana University School of Medicine, Department of Surgery, 545 Barnhill Drive, EH523, Indianapolis, IN 46202, USA. Tel.: +1 317 274 3205; Fax: +1 317 278 1962; E-mail: [email protected].
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.
Keywords: CD20+, CD19+CD5+, CD19+CD27+, CD19+CD27-, lymphocyte subsets, memory B cells, naïve B cells, rituximab, renal failure, T cells
