Impact of FCGR2A R131H, FCGR3A F158V and FCGR3B NA1/NA2 polymorphisms on response to Fc-containing TNF inhibitors in Tunisian rheumatoid arthritis patients.

Abstract

Objectives: Single nucleotid polymorphisms (SNPs) of Fc-gamma receptors (FcgRs), by inducing a variation of their affinity to the Fc-region of immunoglobulins, might influence the efficacy of Fc-containing biologics prescribed in rheumatoid arthritis (RA). Our aim was to investigate associations of FCGR2A, FCGR3A and FCGR3B SNPs with TNF-inhibitors (TNFi)' response in Tunisian RA patients.

Methods: A cross-sectional, observational and analytic multicentric cohort study was conducted in a group of 47 Tunisian RA patients treated with (etanercept [ETA], adalimumab [ADL] and infliximab [IFX]). Treatment outcome was evaluated after 6 months. R131H-FCGR2A, F158V-FCGR3A and NA1/NA2-FCGR3B SNPs were genotyped.

Results: The analytic study including all types of TNFi showed that FCGR3A-F/F low-affinity receptor was associated with a greater decrease of DAS28, while FCGR3B-NA1/NA1 high-affinity receptor was associated with a lower decrease of DAS28 in ADL group. Furthermore, both of high affinity receptors FCGR3B-NA1/NA1 and FCGR3A-V/V were more prevalent in non-responders to ADL, according to EULAR criteria.

Conclusions: Identifying reliable biomarkers of response to biologics in RA is necessary to improve responsiveness, preserve joints' functions and structure, and reduce treatment's cost. Our study showed that FCGR3A and FCGR3B polymorphisms might have an impact on TNFis' response in RA Tunisian patients since bad response was more frequent in homozygous carriers of high affinity alleles FCGR3A-V and FCGR3B-NA1.