Influence of variants of Fc gamma receptors IIA and IIIA on the American College of Rheumatology and European League Against Rheumatism responses to anti-tumour necrosis factor alpha therapy in rheumatoid arthritis.

OBJECTIVE: Fc gamma receptor (Fc gammaR) polymorphism influences the affinity of the receptor for Ig, which may, in turn, affect the efficacy of Ig-based therapies. The relationship between functional single nucleotide polymorphisms (SNP) of the FCGR2A and FCGR3A genes and the response to anti-tumour necrosis factor (TNF)alpha therapy (infliximab) in patients with rheumatoid arthritis (RA) was assessed.

METHODS: A total of 91 patients with RA (89% female; 76.7% rheumatoid factor (RF) positive) starting therapy with infliximab were evaluated at 0, 6 and 30 weeks using the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria and the 28-joint Disease Activity Score (DAS28) was evaluated using three parameters, including C-reactive protein (CRP) (DAS28 3v-CRP) changes during the follow-up. Genotyping of FCGR2A-R131H and FCGR3A-F158V polymorphisms was performed by allele-specific PCR and PCR sequence-based typing, respectively. The chi(2) and Fisher exact tests were used to show differences in the outcome variables, and analysis of variance (ANOVA) to analyse the evolution of DAS28 3v-CRP. A generalised linear models multivariable analysis was also performed.

RESULTS: At week 6 of follow-up, the proportion of patients achieving 50% improvement as per ACR criteria (ACR50) and EULAR good responses were significantly higher among homozygotes of the low affinity FCGR3A allele (FF: 24.1% and VV-VF:2.2%; p = 0.003 and FF: 44.8% and VV-VF: 22.9%; p = 0.040, respectively). At week 30, homozygotes of the low affinity FCGR2A allele had a better ACR20 response (RR: 60% and HH-RH: 33.3%; p = 0.035). Changes in DAS28 3v-CRP during follow-up were consistent with those observed in ACR and EULAR responses.

CONCLUSIONS: The response to anti-TNFalpha treatment with infliximab in patients with RA is influenced by the FCGR2A and FCGR3A genotypes. This effect is observed at different times in the follow-up (6 and 30 weeks, respectively) indicating the dynamic nature of the Fc gammaR versus Ig interaction.