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

• Published in: Human antibodies Vol. 13; no. 3; pp. 55 - 62
• Main Authors: Sidner, Richard A., Book, Benita K., Agarwal, Avinash, Bearden, Christopher M., Vieira, Carlos A., Pescovitz, Mark D.
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 2004
• Subjects: Adult; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Murine-Derived; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - pathology; Female; Humans; Lymphocyte Count; Lymphocyte Depletion; Male; Middle Aged; Renal Dialysis; Rituximab; Time Factors; CD20; lymphocyte subsets; CD19+CD27; renal failure; CD19+CD5; naïve B cells; memory B cells; T cells; rituximab
• ISSN: 1093-2607; 1875-869X
• DOI: 10.3233/HAB-2004-13301

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.