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Influence of variants of Fcγreceptors IIA and IIIA on the ACR and EULAR responses to anti-TNFα therapy in rheumatoid arthritis
  1. Juan D Cañete (jcanete{at}clinic.ub.es)
  1. Hospital Clinic, Spain
    1. Belén Suarez
    1. Rheumatology Dept, Hospital Clínic de Barcelona, Spain
      1. Maria V Hernández
      1. Rheumatology Dept, Hospital Clínic de Barcelona, Spain
        1. Raimon Sanmartí (sanmarti{at}clinic.ub.es)
        1. Rheumatology Dept, Hospital Clínic de Barcelona, Spain
          1. Ignacio Rego
          1. Rheumatology Dept, Hospital Juan Canalejo, A Coruña, Spain
            1. Raquel Celis
            1. Rheumatology Dept, Hospital Clínic de Barcelona, Spain
              1. Concepción Moll
              1. Rheumatology Dept, Hospital Clínic de Barcelona, Spain
                1. José A Pinto
                1. Rheumatology Dept, Hospital Juan Canalejo, A Coruña, Spain
                  1. Francisco J Blanco
                  1. Rheumatology Dept, Hospital Juan Canalejo, A Coruña, Spain
                    1. Francisco Lozano
                    1. Immunology Dept, Hospital Clínic de Barcelona, Spain

                      Abstract

                      Aims: Fc gamma receptor (FcγR) polymorphism influences the receptors’ affinity for immunoglobulins (Ig), which may, in turn, affect the efficacy of Ig-based therapies. We assessed the relationship between functional single-nucleotide polymorphisms (SNP) of the FCGR2A and FCGR3A genes and the response to anti-TNFα therapy (infliximab) in patients with rheumatoid arthritis (RA).

                      Methods: 91 RA patients (89% female; 76.7% RF positive) starting therapy with infliximab were evaluated at 0, 6 and 30 weeks using the ACR and EULAR response criteria and the DAS28 was evaluated using 3 parameters including 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-square and Fisher’s exact tests were used to show differences in the outcome variables, and ANOVA to analyze the evolution of DAS28 3v-CRP. A generalized linear models multivariable analysis was also performed.

                      Results: At week 6 of follow-up, the proportion of patients achieving 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 both 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.

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