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Systemic Lupus Erythematosus
Effect of long-term belimumab treatment on b cells in systemic lupus erythematosus: Extension of a phase II, double-blind, placebo-controlled, dose-ranging study†
Article first published online: 28 DEC 2009
Copyright © 2010 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 62, Issue 1, pages 201–210, January 2010
How to Cite
Jacobi, A. M., Huang, W., Wang, T., Freimuth, W., Sanz, I., Furie, R., Mackay, M., Aranow, C., Diamond, B. and Davidson, A. (2010), Effect of long-term belimumab treatment on b cells in systemic lupus erythematosus: Extension of a phase II, double-blind, placebo-controlled, dose-ranging study. Arthritis & Rheumatism, 62: 201–210. doi: 10.1002/art.27189
ClinicalTrials.gov identifier: NCT00071487.
- Issue published online: 28 DEC 2009
- Article first published online: 28 DEC 2009
- Manuscript Accepted: 2 OCT 2009
- Manuscript Received: 5 MAY 2009
- Irvington Institute Fellowship Program of the Cancer Research Institute
- National Institute of Allergy and Infectious Diseases. Grant Numbers: R01-AI-049660, ACE U19-56-390
- National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grant Number: R01-AR-049938-01
- National Institute of Allergy and Infectious Diseases. Grant Numbers: ACE U19-AI-56362, P01-AI-51392
To understand the effects of long-term BLyS inhibition in human systemic lupus erythematosus (SLE).
Seventeen patients with SLE who were enrolled in a clinical trial of belimumab, a BLyS-specific inhibitor, plus standard of care therapy were studied. Phenotypic analysis of lymphocytes was performed using flow cytometry. Circulating antibody-secreting cells were enumerated using enzyme-linked immunospot assay. Serum was analyzed by enzyme-linked immunosorbent assay using an antibody that recognizes products of the VH4–34 gene. Lymphocyte counts, Ig levels, and anti–double-stranded DNA antibody levels were available as part of the clinical trial analyses.
Samples were collected on days 0, 84, 168, 365, and 532 and after day 730. The total number of B cells started to decrease from baseline between days 84 and 168. This was due to a decrease in naive and transitional B cells. CD27+IgD+ memory B cells and plasmablasts decreased only after 532 days, whereas CD27+IgD− memory B cells were not affected, and there were no changes in T cells. Serum IgM levels began to decline between days 84 and 168, but there were no changes in serum levels of IgG, IgG anti-DNA antibodies, or VH4–34 antibodies during the study. SLE patients had more IgM-, IgG-, and autoantibody-producing B cells than did normal controls on day 0. There was only a modest decrease in the frequency of total IgM-producing, but not IgG-producing, cells on days 365 and 532, consistent with the phenotypic and serologic data.
Our data confirm the dependence of newly formed B cells on BLyS for survival in humans. In contrast, memory B cells and plasma cells are less susceptible to selective BLyS inhibition.