OP0123 IL2RA is Associated with Persistence of Rheumatoid Arthritis
Authors: H.W. van Steenbergen, J.A. van Nies, T.W. Huizinga, A. Cantagrel, F. Berenbaum, A.H. van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Chronic inflammation is a hallmark of rheumatoid arthritis (RA). Thus far, the biologic mechanisms underlying disease persistence are largely unknown. A proportion of RA-patients achieve DMARD-free sustained remission (persistent absence of arthritis after cessation of DMARD-therapy) over time, reflecting loss of disease persistence. To identify genetic variants indicative for processes underlying disease persistence we performed a candidate gene study. We hypothesized that variants associating with lack of radiographic progression also associate with DMARD-free sustained remission. <h3>Methods</h3> 645 Dutch RA-patients were studied on achieving DMARD-free sustained remission during a maximal follow-up of 10-years. Variants replicated to be associated with radiographic progression under an additive model (<i>HLA-DRB1-</i>shared epitope (SE), <i>DKK1</i>-rs1896368, <i>DKK1</i>-rs1896367, <i>DKK1</i>-rs1528873, <i>C5Orf30</i>-rs26232, <i>IL2RA</i>-rs2104286, <i>MMP-</i>9-rs11908352, rs451066 and <i>OPG</i>-rs1485305) were studied. Cox-regression analyses were performed and Bonferroni correction applied. Soluble IL2RA (sIL2Ra)-levels were studied in relation to remission. For replication, 622 RA-patients included in the ESPOIR cohort were studied. Results were combined in inverse-variance weighted meta-analysis. <h3>Results</h3> 119 patients achieved DMARD-free sustained remission after median disease duration of 4.3 years. The SE-alleles associated with a lower chance on remission, similar as previously reported (hazard ratio (HR)=0.57 95% confidence interval (95%CI)=0.42-0.77 p=2.72x10<sup>-4</sup>). Variants in <i>DKK-1</i>, <i>C5orf30</i>, <i>MMP-9</i> and <i>OPG</i> were not associated with remission. The <i>IL2RA</i>-rs2104286 minor allele associated with a higher chance on remission (HR=1.52 95%CI=1.16-1.99 p=2.44x10<sup>-3</sup>), also after additional adjustment for anti-citrullinated peptide antibody status (HR=1.47, 95%CI=1.12-1.93, p=5.78x10<sup>-3</sup>). The rs2104286 minor allele associated with lower sIL2Ra-levels (p=1.43x10<sup>-3</sup>) and lower sIL2Ra-levels associated with a higher chance on remission (HR=0.81 per 100 pg/L 95%CI=0.68-0.95 p=0.012). When including both rs2104286 and sIL2Ra-levels in one analysis the HR for rs2104286 was 2.27 (95%CI=1.06-4.84 p=0.034) and for sIL2Ra 0.83 per 100 pg/L (95%CI=0.70-0.98 p=0.026). Within ESPOIR, the HR of rs2104286 was 1.31 (95%CI=0.90-1.90). Meta-analysis of the two cohorts revealed a p-value of 1.01x10<sup>-3</sup>. <h3>Conclusions</h3> <i>IL2RA</i>-rs2104286 and sIL2Ra-level associated with loss of disease persistence in RA. Variants in <i>IL2RA</i> are known to protect against development of multiple sclerosis, diabetes and RA. Present data revealed that <i>IL2RA</i>-rs2104286, in addition to <i>HLA</i>-SE, is the only genetic factor that is associated with both radiographic joint destruction and RA-persistence. This underlines the relevance of <i>IL2RA</i> for RA. <h3>Disclosure of Interest</h3> None declared