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  • 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

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Clinical and epidemiological research
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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.

http://dx.doi.org/10.1136/ard.2008.096982

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    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.