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

Ines Mahmoud; Myriam Moalla; Aicha Ben Tekaya; Selma Bouden; Leila Rouached; Rawdha Tekaya; Olfa Saidane; Yousr Gorji; Mohamed Elleuch; Ahmed Laatar; Wafa Hamdi; Leila Abdelmoula; Imen Sfar

doi:10.1515/dmpt-2022-0176

Article

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

Ines Mahmoud , Myriam Moalla , Aicha Ben Tekaya , Selma Bouden , Leila Rouached , Rawdha Tekaya , Olfa Saidane , Yousr Gorji , Mohamed Elleuch , Ahmed Laatar , Wafa Hamdi , Leila Abdelmoula and Imen Sfar

Published/Copyright: March 16, 2023

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From the journal Drug Metabolism and Personalized Therapy Volume 38 Issue 2

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.

Keywords: Fc-gamma receptor; polymorphism; responsiveness; rheumatoid arthritis; TNF blockers

Corresponding author: Myriam Moalla, MD, Rheumatology Department, Charles Nicolle Hospital, Tunis El Manar University, 10/3 Djebal Lakhdher Street, Bab Saadoun, Tunis, Tunisia, Phone: 00216 21690044, E-mail: myriammoalla@live.fr

Research funding: None declared.
Author contributions: Ines Mahmoud: analysis and interpretation of data, reviewing Myriam Moalla: acquisition, analysis and interpretation of data, redaction Ben Tekaya Aicha: verified the analytical methods Bouden Selma: verified the analytical methods Rouached Leila: english review Tekaya Rawdha: reviewing Saidane Olfa: reviewing Gorji Yousr: conception and design Abdelmoula Leila: conception and design Imen Sfar: analysis and interpretation of data, reviewing. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Conflicts of interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study. No children were involved.
Ethical approval: The research related to human use has complied with all the relevant national regulations, institutional policies, and in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ Institutional Review Board: Ethics Committee of Charles Nicole Hospital of Tunis (Reference# ADA103).
Disclaimer: The views expressed in the article are the authors’ and not an official position of the institution or funder.

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Received: 2022-10-27

Accepted: 2022-12-24

Published Online: 2023-03-16

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Articles in the same Issue

https://doi.org/10.1515/dmpt-2022-0176

Keywords for this article

Fc-gamma receptor; polymorphism; responsiveness; rheumatoid arthritis; TNF blockers