title: Circulating levels of B lymphocyte stimulator in patients with rheumatoid arthritis following rituximab treatment: relationships with B cell depletion, circulating antibodies, and clinical relapse.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University College London, London, UK. g.cambridge@ucl.ac.uk
authors.forename: Geraldine
authors.initials: G
authors.lastname: Cambridge
authors.forename: William
authors.initials: W
authors.lastname: Stohl
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Leandro
authors.forename: Thi-Sau
authors.initials: TS
authors.lastname: Migone
authors.forename: David M
authors.initials: DM
authors.lastname: Hilbert
authors.forename: Jonathan C W
authors.initials: JC
authors.lastname: Edwards
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood*; D000907:Antibodies, Bacterial / Q000097:blood; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19 / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D012008:Recurrence; D012217:Rheumatoid Factor / Q000097:blood; D000069283:Rituximab; D014409:Tumor Necrosis Factor-alpha
chemical_list: D000906:Antibodies; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D001323:Autoantibodies; D053264:B-Cell Activating Factor; D008565:Membrane Proteins; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; D012217:Rheumatoid Factor