Article Text

PDF
OP0123 IL2RA is Associated with Persistence of Rheumatoid Arthritis
  1. H.W. van Steenbergen1,
  2. J.A. van Nies1,
  3. T.W. Huizinga1,
  4. A. Cantagrel2,
  5. F. Berenbaum3,
  6. A.H. van der Helm-van Mil1
  1. 1Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands
  2. 2Rheumatology Center, Toulouse University Hospital, Toulouse
  3. 3University of Paris 06 UPMC, INSERM UMRS-938, Department of Rheumatology, hospital Saint-Antoine AP-HP, Paris, France

Abstract

Background 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.

Methods 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 (HLA-DRB1-shared epitope (SE), DKK1-rs1896368, DKK1-rs1896367, DKK1-rs1528873, C5Orf30-rs26232, IL2RA-rs2104286, MMP-9-rs11908352, rs451066 and OPG-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.

Results 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=2.72x10-4). Variants in DKK-1, C5orf30, MMP-9 and OPG were not associated with remission. The IL2RA-rs2104286 minor allele associated with a higher chance on remission (HR=1.52 95%CI=1.16-1.99 p=2.44x10-3), also after additional adjustment for anti-citrullinated peptide antibody status (HR=1.47, 95%CI=1.12-1.93, p=5.78x10-3). The rs2104286 minor allele associated with lower sIL2Ra-levels (p=1.43x10-3) 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 1.01x10-3.

Conclusions IL2RA-rs2104286 and sIL2Ra-level associated with loss of disease persistence in RA. Variants in IL2RA are known to protect against development of multiple sclerosis, diabetes and RA. Present data revealed that IL2RA-rs2104286, in addition to HLA-SE, is the only genetic factor that is associated with both radiographic joint destruction and RA-persistence. This underlines the relevance of IL2RA for RA.

Disclosure of Interest None declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.