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

Authors

  • Annett M. Jacobi,

    1. University Hospital Munster, Munster, Germany), Weiqing Huang, MD, Tao Wang, BSc, Meggan Mackay, MD, Cynthia Aranow, MD, Betty Diamond, MD, Anne Davidson, MBBS: Feinstein Institute for Medical Research, Manhasset, New York
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  • Weiqing Huang,

    1. University Hospital Munster, Munster, Germany), Weiqing Huang, MD, Tao Wang, BSc, Meggan Mackay, MD, Cynthia Aranow, MD, Betty Diamond, MD, Anne Davidson, MBBS: Feinstein Institute for Medical Research, Manhasset, New York
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  • Tao Wang,

    1. University Hospital Munster, Munster, Germany), Weiqing Huang, MD, Tao Wang, BSc, Meggan Mackay, MD, Cynthia Aranow, MD, Betty Diamond, MD, Anne Davidson, MBBS: Feinstein Institute for Medical Research, Manhasset, New York
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  • William Freimuth,

    1. Human Genome Sciences, Rockville, Maryland
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    • Dr. Freimuth owns stock or stock options in Human Genome Sciences.

  • Inaki Sanz,

    1. University of Rochester, Rochester, New York
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  • Richard Furie,

    1. North Shore–Long Island Jewish Health System, Lake Success, New York
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    • Dr. Furie has received consulting fees, speaking fees, and/or honoraria from Human Genome Sciences (less than $10,000) and has received consulting fees from investment analysts GLG and Guidepoint (less than $10,000).

  • Meggan Mackay,

    1. University Hospital Munster, Munster, Germany), Weiqing Huang, MD, Tao Wang, BSc, Meggan Mackay, MD, Cynthia Aranow, MD, Betty Diamond, MD, Anne Davidson, MBBS: Feinstein Institute for Medical Research, Manhasset, New York
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  • Cynthia Aranow,

    1. University Hospital Munster, Munster, Germany), Weiqing Huang, MD, Tao Wang, BSc, Meggan Mackay, MD, Cynthia Aranow, MD, Betty Diamond, MD, Anne Davidson, MBBS: Feinstein Institute for Medical Research, Manhasset, New York
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  • Betty Diamond,

    1. University Hospital Munster, Munster, Germany), Weiqing Huang, MD, Tao Wang, BSc, Meggan Mackay, MD, Cynthia Aranow, MD, Betty Diamond, MD, Anne Davidson, MBBS: Feinstein Institute for Medical Research, Manhasset, New York
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  • Anne Davidson

    Corresponding author
    1. University Hospital Munster, Munster, Germany), Weiqing Huang, MD, Tao Wang, BSc, Meggan Mackay, MD, Cynthia Aranow, MD, Betty Diamond, MD, Anne Davidson, MBBS: Feinstein Institute for Medical Research, Manhasset, New York
    • Investigator, Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030
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  • ClinicalTrials.gov identifier: NCT00071487.

Abstract

Objective

To understand the effects of long-term BLyS inhibition in human systemic lupus erythematosus (SLE).

Methods

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.

Results

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.

Conclusion

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.

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