title: Efficacy of selective B cell blockade in the treatment of rheumatoid arthritis: evidence for a pathogenetic role of B cells.
abstract: OBJECTIVE
  The pathogenetic role of B cells in rheumatoid arthritis (RA) is under debate, but it is currently believed to be marginal. The availability of selective anti-B cell treatment provides a unique opportunity to clarify this issue. This study was undertaken to investigate the effects of B cell blockade in the treatment of refractory RA, and to evaluate the implications with regard to the role of B cells in the disease.
  
  
  METHODS
  Five female patients with active, evolving erosive RA were treated with rituximab, an anti-CD20 chimeric monoclonal antibody. All 5 patients had been nonresponders to combination therapy with methotrexate plus cyclosporin A. Two of the 5 had also failed to respond to anti-tumor necrosis factor alpha therapy. All of these treatments were discontinued 1 month before institution of anti-CD20 therapy.
  
  
  RESULTS
  Marked clinical improvement was observed in 2 patients (American College of Rheumatology 70% response [ACR70] and ACR50, respectively), starting at the end of the second month after institution of anti-CD20 therapy (month 2) and lasting until month 10 in 1 patient (articular relapse) and month 12 in the other (last followup). ACR20 response was observed in 2 additional patients, lasting until month 5 and month 7, respectively (articular relapse in both). Decrease or normalization of serum C-reactive protein and rheumatoid factor levels were observed in these patients. In contrast, patient 3 had no response to the treatment. RA synovitis and evolving erosive damage were decreased in patients exhibiting a major response, as demonstrated by imaging studies.
  
  
  CONCLUSIONS
  Our finding of the clinical efficacy of selective B cell blockade indicates that B cells play a critical role in rheumatoid synovitis, at least in a subset of patients. Qualitative or quantitative differences in B cell commitment in RA pathobiology might have a function in the different responses observed.
authors.affiliation: University of Udine, Udine, Italy. gf.ferraccioli@med.uniud.it
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Vita
authors.forename: Francesco
authors.initials: F
authors.lastname: Zaja
authors.forename: Stefania
authors.initials: S
authors.lastname: Sacco
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Candia
authors.forename: Renato
authors.initials: R
authors.lastname: Fanin
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Ferraccioli
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D007262:Infusions, Intravenous; D008875:Middle Aged; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D000069283:Rituximab