title: RF positivity has substantial influence on the peripheral memory B-cell compartment and its modulation by TNF inhibition.
abstract: OBJECTIVE
  The role of B cells in rheumatoid arthritis (RA) has been well established with the advent of B-cell targeted therapies. Alterations of peripheral B-cell subsets in RA and heterogeneous modulations of the B-cell compartment under tumour necrosis factor (TNF) inhibition have been described. In this study we examined the influence of rheumatoid factor (RF) positivity on the peripheral B-cell compartment and its modulation under TNF blockade.
  
  
  METHODS
  Consecutive patients with RA and inadequate response to methotrexate (MTX) were stratified according to RF status and a subset of them was included in a prospective study of weekly etanercept treatment.
  
  
  RESULTS
  At baseline, RF-negative patients had a significant higher percentage of overall CD27+ B cells compared to healthy controls (HC) and RF-positive patients. In detail, RF-negative patients had 46.6% (range 15.7-86.8%) CD27+ B cells compared to 31.3% (12.9-56.9%, p = 0.026) in HC and 29.8% (19-73.3%, p = 0.04) in RF-positive patients. Within the CD27+ compartment, CD27+/immunoglobulin (Ig)D+ memory B cells were significantly increased to 26.4% (range 5.9-54.7%) in RF-negative patients compared to 14.9% (4.1-27.3%, p = 0.006) in HC and 10.5% (3.4-41.1%, p = 0.003) in RF-positive patients. During anti-TNF therapy, memory B cells increased significantly in relative and absolute numbers only in RF-negative patients.
  
  
  CONCLUSIONS
  In RF-negative patients, we observed an enhanced frequency of peripheral memory B cells and an accumulation of pre-switch memory B cells. During anti-TNF therapy, memory B cells increased significantly only in RF-negative patients, suggesting that the peripheral memory B-cell compartment is more amenable to TNF inhibition in these patients.
authors.affiliation: Department of Medicine II, Rheumatology and Clinical Immunology, University of Würzburg, Germany. Roll_P@medizin.uni-wuerzburg.de
authors.forename: P
authors.initials: P
authors.lastname: Roll
authors.forename: K
authors.initials: K
authors.lastname: Muhammad
authors.forename: M
authors.initials: M
authors.lastname: Schumann
authors.forename: S
authors.initials: S
authors.lastname: Kleinert
authors.forename: H-P
authors.initials: HP
authors.lastname: Tony
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D016022:Case-Control Studies; D000068800:Etanercept; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012217:Rheumatoid Factor / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha; D012217:Rheumatoid Factor; D000068800:Etanercept