Fcγ receptor type IIIA polymorphisms influence treatment outcomes in patients with inflammatory arthritis treated with tumor necrosis factor α–blocking agents

Abstract

Objective. To determine whether polymorphisms in Fc␥ receptor type IIIA (Fc␥RIIIA) correlate with clinical efficacy in patients with rheumatoid arthritis (RA) and patients with psoriatic arthritis (PsA) being treated with tumor necrosis factor ␣ (TNF␣) 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 Fc␥RIIIA analysis. The Fc␥RIIIA-158 polymorphism was determined using an allele-specific polymerase chain reaction assay.Results. The distribution of Fc␥RIIIA-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 Fc␥RIIIA-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.

A single-nucleotide polymorphism of the Fcγ receptor type IIIA gene in the recipient predicts transplant outcomes after HLA fully matched unrelated BMT for myeloid malignancies

“…14 The cells bearing the FCGR3A-158V genotype show a higher affinity for IgG1 and IgG3 than those without 158V, and are capable of binding IgG4, 15 and thus can exert Ab-dependent cell-mediated cytotoxicity more efficiently. 16 The 158V genotype is associated with susceptibility to rheumatoid arthritis 17 and immune-mediated thrombocytopenic purpura, 18 better clinical response to rituximab in B-cell lymphomas 19,20 and a lower risk of recurrent periodontitis. 21 In contrast, systemic lupus erythematosus and better clinical outcome of cetuximab against metastatic colorectal cancer correlates with the 158F genotype.…”

Pharmacokinetic study and Fcγ receptor gene analysis in two patients with rheumatoid arthritis controlled by low-dose infliximab

“…The genotype of FccRIIIA in both of our patients was 176F/F. Tutuncu et al [19] investigated FccRIIIA polymorphism in 35 RA patients and found that 11 patients with the 176F/F genotype were all responders. Since the affinity of FccRIIIA-176F for IgG is lower than that of FccRIIIA-176V, the clearance of infliximab may be decreased.…”

Anti-TNFα domain antibody construct CEP-37247

“…24,25 It has been demonstrated that infliximab and adalimumab, but not etanercept, act on cells expressing the cellular membrane-bound form of TNFα by binding to the TNFα on these cells via the variable regions of the antibody and recruiting effector cells through interaction of the Fc region of the antibody with FcγRII and FcγRIII receptors on effector cells. 26 We investigated whether CEP-37247 was capable of binding to membrane-associated TNFα.…”