Article Text

PDF
Extended report
Influence of variants of Fcγ receptors IIA and IIIA on the American College of Rheumatology and European League Against Rheumatism responses to anti-tumour necrosis factor α therapy in rheumatoid arthritis
  1. J D Cañete1,
  2. B Suárez2,
  3. M V Hernández1,
  4. R Sanmartí1,
  5. I Rego3,
  6. R Celis1,
  7. C Moll1,
  8. J A Pinto3,
  9. F J Blanco3,
  10. F Lozano2
  1. 1
    Rheumatology, Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), School of Medicine, University of Barcelona, Barcelona, Spain
  2. 2
    Immunology Departments, Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), School of Medicine, University of Barcelona, Barcelona, Spain
  3. 3
    Rheumatology Department, Hospital Juan Canalejo, La Coruña, Spain
  1. Correspondence to J D Cañete, Unitat d’Artritis, Servei de Reumatologia, Hospital Clínic de Barcelona, Villarroel 170, 08036 Barcelona, Spain; jcanete{at}clinic.ub.es

Abstract

Objective: Fcγ receptor (FcγR) 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)α 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 χ2 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-TNFα 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 FcγR versus Ig interaction.

Statistics from Altmetric.com

Footnotes

  • Funding This work was supported by Fondo de Investigación Sanitaria (JDC: PI04/1023, PI041027). JDC was also supported by a research grant from Fundación Española de Reumatología (programa DIB/SER). FLS was supported by a grant from the Spanish Research Network on Infectious Diseases (REIPI, RD06/0008/1013) from Instituto de Salud Carlos III.

  • Competing interests None.

  • Ethics approval The Ethics Committee of the Hospital Clínic approved the study and written informed consent was obtained from all participants.

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.