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AB0242 IL6 Genetic Variants and IGA-RF as Markers of Erosiveness at Onset in Early Rheumatoid Arthritis
  1. S. Canestri,
  2. A.L. Fedele,
  3. B. Tolusso,
  4. L. Petricca,
  5. S. Alivernini,
  6. M.R. Gigante,
  7. E. Gremese,
  8. G. Ferraccioli
  1. Institute of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy

Abstract

Objectives To determine whether genetic variants in the loci of interleukin-6 (IL-6) are associated with clinical and biologic phenotypes of Rheumatoid Arthritis (RA).

Methods Three hundred and forty five early RA (ERA) patients were enrolled in this study (76.2% female; mean age: 54.4±14.1 years; 33.6% VERA). 239 patients (69.3%) were seropositive for at least one antibody: 62.9% ACPA, 48.7% RF -IgM and 33.0% RF-IgA positive, respectively. At diagnosis, 101 subjects (29.3%) had detectable erosions in hands and feet radiographs. All patients were treated according to a tight control strategy (Methotrexate for 3 months, and if an incomplete response was reached after 3 months a combination with Tumor Necrosis Factor (TNF) blockers was started) and at each visit, clinical remission was evaluated according to ACR/EULAR criteria (Felson DT et al. Arthritis Rheum 2011). ERA patients were genotyped for IL6–174G/C polymorphism by PCR and compared with a cohort of healthy subjects (n=293).

Results The frequency of C allele of the IL-6–174G/C SNP was higher in ERA patients (30.7%) compared to healthy controls [23.7%; OR (95%CIs): 1.43 (1.11–1.83)], while the GG genotype was present in 49.6% of ERA and in 59.4% of control subjects [OR (95%CIs): 0.67 (0.49–0.92)] respectively. At baseline, ERA patients carriers of the GG genotype were more likely seropositive compared to patients carrying the C allele [74.9% vs 63.8%, p=0.03], mainly for the IgA-RF positivity [38.6% vs 27.7%; OR (95%CIs): 1.64 (1.04–2.57)]. At diagnosis, IgA-RF positive ERA patients were more likely erosive than IgA-RF negative ones [33.1% vs 25.2%; OR (95%CIs):1.80 (1.11–2.95)]. Conversely, radiographic damage was not associated with gender, symptoms duration, smoking habit, positivity for ACPA or IgM-RF antibodies and disease activity. The percentage of erosive disease increased to 39.6% in ERA patients IgA-RF + carrying the GG genotype compared to the others (24.7%; OR (95%CIs): 2.002 (1.23–3.26)], with a lower presence of radiographic damage in carriers of C allele and IgA-RF negative (12.5%). Finally, patients carrying C allele of IL6–174G/C SNP and IgA- RF negative at diagnosis, were less prone to develop erosions over time than subjects with at least one risk factor (8.0% vs 19.1%, respectively, p=0.02).

Conclusions In our cohort of ERA patients, the presence of C allele of IL6–174G/C SNP associates with RA susceptibility whereas the GG genotype associates with seropositivity for IgA-RF and erosions. These data add new information about the biology underlying the development of radiographic damage in the early phases of RA.

Disclosure of Interest None declared

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