Circulating levels of B lymphocyte stimulator in patients with rheumatoid arthritis following rituximab treatment: Relationships with B cell depletion, circulating antibodies, and clinical relapse

Authors

  • Geraldine Cambridge,

    Corresponding author
    1. University College London, London, UK
    • University College London, Arthur Stanley House, Tottenham Street, London W1T 4NJ, UK
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  • William Stohl,

    1. University of Southern California Keck School of Medicine, Los Angeles
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    • Dr. Stohl has received consulting fees (less than $10,000 per year) from Human Genome Sciences. Dr. Leandro has received honoraria (less than $10,000 per year) from Roche. Dr. Hilbert owns HGSI stock. Dr. Edwards has received consulting fees (less than $10,000 per year), staff support, and a supply of rituximab from Roche.

  • Maria J. Leandro,

    1. University College London, London, UK
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    • Dr. Stohl has received consulting fees (less than $10,000 per year) from Human Genome Sciences. Dr. Leandro has received honoraria (less than $10,000 per year) from Roche. Dr. Hilbert owns HGSI stock. Dr. Edwards has received consulting fees (less than $10,000 per year), staff support, and a supply of rituximab from Roche.

  • Thi-Sau Migone,

    1. Human Genome Sciences, Rockville, Maryland
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  • David M. Hilbert,

    1. Human Genome Sciences, Rockville, Maryland
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    • Dr. Stohl has received consulting fees (less than $10,000 per year) from Human Genome Sciences. Dr. Leandro has received honoraria (less than $10,000 per year) from Roche. Dr. Hilbert owns HGSI stock. Dr. Edwards has received consulting fees (less than $10,000 per year), staff support, and a supply of rituximab from Roche.

  • Jonathan C. W. Edwards

    1. University College London, London, UK
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    • Dr. Stohl has received consulting fees (less than $10,000 per year) from Human Genome Sciences. Dr. Leandro has received honoraria (less than $10,000 per year) from Roche. Dr. Hilbert owns HGSI stock. Dr. Edwards has received consulting fees (less than $10,000 per year), staff support, and a supply of rituximab from Roche.


Abstract

Objective

To assess the effects of B lymphocyte depletion on serum B lymphocyte stimulator (BLyS; trademark of Human Genome Sciences, Rockville, MD) levels in patients with rheumatoid arthritis (RA), and to assess the relationship of serum BLyS levels with peripheral blood B cell depletion, levels of autoantibodies and antimicrobial antibodies, the return of peripheral blood B cells, and clinical relapse.

Methods

Fifteen patients with active RA underwent rituximab-based B cell depletion therapy (BCDT). Disease activity was assessed clinically, peripheral blood CD19+ B cell counts were determined by flow cytometry, and serum levels of BLyS, IgM, IgA, and IgG rheumatoid factors (RFs), anti–cyclic citrullinated peptide, and antimicrobial antibodies were assessed using enzyme-linked immunosorbent assays.

Results

Peripheral blood B cell depletion was achieved in all 15 patients, and an American College of Rheumatology 20% response was achieved in 13 patients. Following clinical relapse, 7 patients underwent at least 1 additional cycle of BCDT. In every case, serum BLyS levels markedly rose post-BCDT and remained elevated for at least 1–2 months. Serum levels of RF, but not those of anti–tetanus toxoid or anti–pneumococcal polysaccharide antibodies, fell significantly. A decline in serum BLyS levels was associated with the reemergence of B cells in peripheral blood, which, in turn, antedated clinical relapse by variable periods of time. The patterns of B cell depletion, serum BLyS and antibody levels, and clinical relapse for each BCDT cycle were remarkably similar in re-treated patients.

Conclusion

Rituximab-based BCDT leads to marked increases in serum BLyS levels. This may contribute significantly to the survival and/or regeneration of B cell populations capable of triggering clinical relapse.

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