Authors: Sidner, Richard A. | Book, Benita K. | Agarwal, Avinash | Bearden, Christopher M. | Vieira, Carlos A. | Pescovitz, Mark D.
Article Type:
Research Article
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.
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Keywords: CD20+, CD19+CD5+, CD19+CD27+, CD19+CD27-, lymphocyte subsets, memory B cells, naïve B cells, rituximab, renal failure, T cells
DOI: 10.3233/HAB-2004-13301
Citation: Human Antibodies,
vol. 13, no. 3, pp. 55-62, 2004
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