title: Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis.
abstract: OBJECTIVE
  To explore the changes in serologic variables and clinical disease activity following B lymphocyte depletion in 22 patients with rheumatoid arthritis (RA).
  
  
  METHODS
  B lymphocyte depletion was attained using combination therapy based on the monoclonal anti-CD20 antibody rituximab. Levels of a serologic indicator of inflammation, C-reactive protein (CRP), of antimicrobial antibodies, of autoantibodies including IgA-, IgM-, and IgG-class rheumatoid factors (RF), and of antibodies to cyclic citrullinated peptide (anti-CCP) were assayed.
  
  
  RESULTS
  The majority of patients showed a marked clinical improvement after treatment with rituximab, with benefit lasting up to 33 months. Levels of total serum immunoglobulins fell, although the mean values each remained within the normal range. Whereas the IgM-RF response paralleled the changes in total serum IgM levels, the levels of IgA-RF, IgG-RF, and IgG and anti-CCP antibodies decreased significantly more than did those of their corresponding total serum immunoglobulin classes. The kinetics for the reduction in CRP levels also paralleled the decreases in autoantibody levels. In contrast, levels of antimicrobial antibodies did not change significantly. B lymphocyte return occurred up to 21 months posttreatment. The time to relapse after B lymphocyte return was often long and unpredictable (range 0-17 months). Relapse was, however, closely correlated with rises in the level of at least one autoantibody. Increased autoantibody levels were rarely observed in the absence of clinical change.
  
  
  CONCLUSIONS
  Following B lymphocyte depletion in patients with RA, a positive clinical response occurred in correlation with a significant drop in the levels of CRP and autoantibodies. Antibacterial antibody levels were relatively well maintained. B lymphocyte return preceded relapse in all patients. There was also a temporal relationship between clinical relapse and rises in autoantibody levels. Although these observations are consistent with a role for B lymphocytes in the pathogenesis of RA, the precise mechanisms involved remain unclear.
authors.affiliation: Centre for Rheumatology, University College London, Arthur Stanley House, 40-50 Tottenham Street, London W1T 4NJ, UK.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Cambridge
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Leandro
authors.forename: Jonathan C W
authors.initials: JC
authors.lastname: Edwards
authors.forename: Michael R
authors.initials: MR
authors.lastname: Ehrenstein
authors.forename: Martin
authors.initials: M
authors.lastname: Salden
authors.forename: Mark
authors.initials: M
authors.lastname: Bodman-Smith
authors.forename: Anthony D B
authors.initials: AD
authors.lastname: Webster
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002097:C-Reactive Protein / Q000378:metabolism; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage; D012008:Recurrence; D012217:Rheumatoid Factor / Q000097:blood; D000069283:Rituximab
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D018501:Antirheumatic Agents; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D000069283:Rituximab; D003520:Cyclophosphamide; D002097:C-Reactive Protein; D012217:Rheumatoid Factor; D011239:Prednisolone