title: Infliximab treatment shifts the balance between stimulatory and inhibitory Fcgamma receptor type II isoforms on neutrophils in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Human neutrophils express both activating and inhibitory Fcgamma receptors (FcgammaR), and their relative expression determines the inflammatory response to immune complexes. Tumor necrosis factor alpha (TNFalpha) up-regulates the expression of stimulatory FcgammaRIIa on neutrophils in vitro, and amplifies immune complex-induced activation of neutrophils in vivo. This study was undertaken to determine whether TNFalpha blockade in patients with rheumatoid arthritis (RA) alters the balance of activating FcgammaR and inhibitory FcgammaR and thereby decreases inflammation.
  
  
  METHODS
  We used fluorescence-activated cell sorting and Western blotting to examine FcgammaR expression on neutrophils in 24 patients with RA, preceding their first infusion of infliximab and immediately prior to >or=3 subsequent infusions.
  
  
  RESULTS
  In 13 of 24 patients (54.2%), there was a decrease in the expression of the predominant activating FcgammaR, FcgammaRIIa, after treatment with infliximab, an effect that persisted over >or=3 months of treatment. Although prior to initiation of infliximab therapy the inhibitory FcgammaR, FcgammaRIIb, was undetectable in neutrophils from 23 of 24 patients with RA, FcgammaRIIb protein was detected by Western blotting in 9 patients (37.5%) at the time of the third infliximab infusion. The induction of inhibitory FcgammaRIIb was always associated with decreased levels of FcgammaRIIa, and improvement following infliximab therapy, measured using the Health Assessment Questionnaire, was significantly associated with down-regulation of FcgammaRIIa.
  
  
  CONCLUSIONS
  Our findings indicate that TNFalpha inhibition may reduce inflammation in patients with RA by restoring the balance of activating and inhibitory FcgammaR and thereby raising the threshold for immune complex-mediated activation of neutrophils.
authors.affiliation: Hospital for Special Surgery, Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Belostocki
authors.forename: Luminita
authors.initials: L
authors.lastname: Pricop
authors.forename: Patricia B
authors.initials: PB
authors.lastname: Redecha
authors.forename: Ani
authors.initials: A
authors.lastname: Aydin
authors.forename: Linda
authors.initials: L
authors.lastname: Leff
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Harrison
authors.forename: Jane E
authors.initials: JE
authors.lastname: Salmon
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D015153:Blotting, Western; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D018501:Antirheumatic Agents; C499173:FCGR2B protein, human; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab