Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Association of IL2RB Polymorphisms with Erosive Disease in ACPA Positive Early Rheumatoid Arthritis (RA): Results from the ESPOIR Cohort.

Ruyssen-Witrand3,  Adeline, Nigon4,  Delphine, Cantagrel5,  Alain G., Lukas7,  Cédric, Morel7,  Jacques, Sibilia6,  Jean, Cambon-Thomsen1,  Anne

Purpose:

RA is a complex disease that leads to joints erosions. The receptor of the Interleukin 2 (IL2R), a cytokine secreted by T lymphocytes implicated in the TH1 differentiation, is a quaternary complex of IL2RA, IL2RB and IL2RG. One SNP of the IL2RA gene (rs 2104286) and 2 SNPs of the IL2RB gene (rs743777 and rs3218253) were previously associated with RA susceptibility. The aim of this study was to assess the impact of these SNPs on the risk of erosions in early RA patients.

Methods:

813 patients with early arthritis (<6 months) were included in a national multicenter prospective study (ESPOIR cohort). Among Caucasian patients, 439 fulfilled the 1987 ACR criteria for RA, had radiographs at inclusion and after one year of follow-up and the 3 SNPs genotyped. Structural damage was quantified according to the Total van der Heijde modified Sharp score (TSS). Erosive RA was defined on an erosion Sharp score (ESS) >0. The 3 IL2RA and IL2RB SNPs were genotyped by KBiosciences (Herts,UK). Statistical analysis: we compared the proportions of patients with erosive disease at baseline and one year among patients carrying the 3 genotypes or the 2 alleles of each SNP using a chi-square test in the whole sample and after stratification on ACPA status. Crude Odds ratios (OR) with 95% confidence interval (95%CI) were calculated according to allele carriage in univariate and multivariate analyses.

Results:

Of the 439 RA patients included (median age: 52 years, 76% of females, median symptom duration: 5 months, median DAS 28: 5.33, rheumatoid factor (RF) positive: 53%, anti-CCP2 positive: 48%), 268 (61%) were erosive at baseline (median TSS=3 [IQR:1–8], median ESS=1 [0–4]) and 287 (65%) at one year (median TSS=4 [1–9], median ESS=2 [0–5]). None genotype of the 3 SNPs was significantly associated with ACPA production.

In the whole RA sample, the IL2RB rs3218253 was significantly associated with erosive status at one year (CC: 69%, CT: 65%, TT:46%, p=0.023) in genotype analysis and at baseline (C allele carriage 63% vs 43%– 0R=2.205 [1.058–4.664]) and one year(C allele carriage 67% vs 46%– 0R=2.406 [1.152–5.059]) in allele carriage analysis.

In ACPA+ patients, the IL2RB rs743777 was significantly associated with erosive status at baseline (AA:71%, AG:71% and GG:36%, p=0.002) and one year (AA:78%, AG:75% and GG:44%, p=0.002) while the IL2RB rs3218253 was significantly associated with erosive status at baseline (CC:74%, CT:66% and TT:30%, p=0.001) and one year (CC:81%, CT:71% and TT:35%, p<0.0001) in genotype analysis.

The A allele of IL2RB rs743777 was significantly associated with the risk of erosion at baseline (71% vs 36%–OR=4.313 [95%CI: 1.663–11.709]) and one year (77% vs 44%–OR=4.203 [95%CI: 1.625–10.972]). The allele C of IL2RB rs3218253 was significantly associated with the risk of erosions at baseline (71% vs 30%–OR=5.583 [1.881–18.490]) and one year (77% vs 35%–OR=6.162 [2.108–19.231]).

The A allele of the IL2RB rs743777 and the C allele of IL2RB rs3218253 remained independently associated with erosive disease in ACPA+ RA patients in multivariate analysis.

Conclusion:

The A allele of the IL2RB rs743777 and the C allele of IL2RB rs3218253 were associated with the risk of erosion in ACPA+ early RA.

To cite this abstract, please use the following information:
Ruyssen-Witrand, Adeline, Nigon, Delphine, Cantagrel, Alain G., Lukas, Cédric, Morel, Jacques, Sibilia, Jean, et al; Association of IL2RB Polymorphisms with Erosive Disease in ACPA Positive Early Rheumatoid Arthritis (RA): Results from the ESPOIR Cohort. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2218
DOI: 10.1002/art.29982

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