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Fcgamma receptor type IIIA polymorphisms influence treatment outcomes in patients with inflammatory arthritis treated with tumor necrosis factor alpha-blocking agents.

Tutuncu Z, Kavanaugh A, Zvaifler N, Corr M, Deutsch R, Boyle D

Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla 92093-0943, USA. Ztutuncu@ucsd.edu

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). CONCLUSION: 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.

Published 12 September 2005 in Arthritis Rheum, 52(9): 2693-6.
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