title: Inflammation-independent defective early B cell tolerance checkpoints in rheumatoid arthritis.
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) patients who have never received treatment for RA have been found to have defective early B cell tolerance checkpoints, resulting in impaired removal of developing autoreactive B cells. However, it is unclear whether these defects in B cell tolerance checkpoints are a primary aspect of the disease or are the result of ongoing inflammatory processes in these patients. The aim of this study was to assess the impact of standard immunosuppressive treatments, methotrexate and anti-tumor necrosis factor α (anti-TNFα) agents, on early B cell tolerance checkpoints in RA patients.
  
  
  METHODS
  Blood samples were obtained from RA patients before and after treatment with methotrexate and/or anti-TNFα agents. B cells were tested pre- and posttherapy for reactivity of recombinant antibodies cloned from single B cells, which allowed us to determine the evolution of the frequency of autoreactive clones in the mature naive B cell compartment in RA patients before and after treatment. B cells from healthy donors were used as controls.
  
  
  RESULTS
  Posttreatment frequencies of autoreactive mature naive B cells were elevated in the blood of RA patients. Nevertheless, the frequencies after treatment remained similar to those observed in the same patients before treatment.
  
  
  CONCLUSIONS
  Despite the achievement of clinical improvement in RA patients following treatment with methotrexate and/or anti-TNFα agents, these therapies did not correct the accumulation of peripheral autoreactive mature naive B cells in these patients, suggesting that inflammation is not responsible for the defective early B cell tolerance checkpoints in RA.
authors.affiliation: Hospital for Special Surgery, New York, New York.
authors.forename: Laurence
authors.initials: L
authors.lastname: Menard
authors.forename: Jonathan
authors.initials: J
authors.lastname: Samuels
authors.forename: Yen-Shing
authors.initials: YS
authors.lastname: Ng
authors.forename: Eric
authors.initials: E
authors.lastname: Meffre
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D001323:Autoantibodies; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate