Circulating Levels of B Lymphocyte Stimulator in Patients With Rheumatoid Arthritis Following Rituximab Treatment: Relationships With B Cell Depletion, Circulating Antibodies, and Clinical Relapse.
Cambridge, Geraldine PhD 1; Stohl, William MD, PhD 2; Leandro, Maria J. MD 1; Migone, Thi-Sau PhD 3; Hilbert, David M. PhD 3; Edwards, Jonathan C. W. MD 1
[Article]
Arthritis & Rheumatism.
54(3):723-732, March 2006.
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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.
(C) 2006, American College of Rheumatology