title: B lymphocyte stimulator expression in patients with rheumatoid arthritis treated with tumour necrosis factor alpha antagonists: differential effects between good and poor clinical responders.
abstract: OBJECTIVE
  To assess the effects of tumour necrosis factor (TNF) antagonist therapy on B lymphocyte stimulator (BLyS) expression in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Blood from 38 patients with RA from a single centre was collected prior to and following initiation of TNF antagonist therapy. Plasma BLyS protein levels, blood leukocyte BLyS mRNA levels and disease activity were longitudinally monitored. Twelve patients with RA who either refused or were felt not to be candidates for TNF antagonist therapy and five normal healthy volunteers served as TNF antagonist-naïve controls.
  
  
  RESULTS
  Baseline plasma BLyS protein levels, but not blood leukocyte BLyS mRNA levels, were elevated in patients with RA. Plasma BLyS protein levels declined following initiation of TNF antagonist therapy in good responders (GR) to TNF antagonist therapy but not in poor responders (PR). By contrast, the erythrocyte sedimentation rate (ESR) declined in response to TNF antagonist therapy in GR and PR. TNF antagonist therapy did not promote change in blood leukocyte BLyS mRNA levels in either GR or PR, suggesting that the TNF antagonist-associated changes in circulating BLyS protein levels reflected changes in local BLyS production in the affected joints rather than changes in systemic BLyS production. BLyS expression did not change over time in either the normal or RA control groups.
  
  
  CONCLUSIONS
  A good clinical response to TNF antagonist therapy in patients with RA is associated with a decline in plasma BLyS protein levels. Increased BLyS expression in affected joints may contribute to ongoing disease activity, and reduction of such expression may help promote a favourable clinical response to TNF antagonist therapy.
authors.affiliation: Division of Rheumatology, Department of Medicine, Los Angeles County and University of Southern California Medical Center and University of Southern California Keck School of Medicine, Los Angeles, California, USA.
authors.forename: D T
authors.initials: DT
authors.lastname: La
authors.forename: C E
authors.initials: CE
authors.lastname: Collins
authors.forename: H-T
authors.initials: HT
authors.lastname: Yang
authors.forename: T-S
authors.initials: TS
authors.lastname: Migone
authors.forename: W
authors.initials: W
authors.lastname: Stohl
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000097:blood* / Q000235:genetics; D001799:Blood Sedimentation; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D015870:Gene Expression; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D053264:B-Cell Activating Factor; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha