title: Fcgamma receptor type IIIA polymorphisms influence treatment outcomes in patients with inflammatory arthritis treated with tumor necrosis factor alpha-blocking agents.
abstract: OBJECTIVE
  To determine whether polymorphisms in Fcgamma receptor type IIIA (FcgammaRIIIA) correlate with clinical efficacy in patients with rheumatoid arthritis (RA) and patients with psoriatic arthritis (PsA) being treated with tumor necrosis factor alpha (TNFalpha) inhibitors.
  
  
  METHODS
  The study group comprised 30 patients with RA and 5 patients with PsA. Patients were classified as being very good responders (n = 23) or nonresponders (n = 12) to therapy with TNF blocking agents. Whole blood was obtained from all patients, and DNA was extracted for FcgammaRIIIA analysis. The FcgammaRIIIA-158 polymorphism was determined using an allele-specific polymerase chain reaction assay.
  
  
  RESULTS
  The distribution of FcgammaRIIIA-158 genotypes was as follows: for F homozygous (F/F), 31.5%; for V homozygous (V/V), 11.5%; and for V/F heterozygous (V/F), 57%. Among very good responders, the distribution of alleles was as follows: for F/F, 48%; for V/V, 13%; and for V/F, 39%. Among nonresponders, the distribution of alleles was as follows: for F/F, 0%; for V/V, 8%; and for V/F, 92%. The low-affinity F/F homozygous genotype was found to be significantly associated with response to TNF inhibitor therapy (P < 0.01 by Fisher's exact test).
  
  
  CONCLUSIONS
  These results suggest that FcgammaRIIIA-158 polymorphisms may affect the outcome of treatment with TNF blocking agents. Better understanding of the factors affecting responses to these agents could result in improved outcomes of treatment.
authors.affiliation: Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla 92093-0943, USA. Ztutuncu@ucsd.edu
authors.forename: Zuhre
authors.initials: Z
authors.lastname: Tutuncu
authors.forename: Arthur
authors.initials: A
authors.lastname: Kavanaugh
authors.forename: Nathan
authors.initials: N
authors.lastname: Zvaifler
authors.forename: Maripat
authors.initials: M
authors.lastname: Corr
authors.forename: Reena
authors.initials: R
authors.lastname: Deutsch
authors.forename: David
authors.initials: D
authors.lastname: Boyle
mesh_terms: D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D015535:Arthritis, Psoriatic / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D007596:Joints / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C496124:FCGR3A protein, human; D007074:Immunoglobulin G; D017452:Receptors, IgG; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept