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IL2RA is associated with persistence of rheumatoid arthritis

H W van Steenbergen1, J A B van Nies2, A Ruyssen-Witrand3

  • 1Department of Rheumatology, Leiden University Medical Center, P.O. Box 9600, 2300, RC, Leiden, The Netherlands. h.w.van_steenbergen@lumc.nl.

Arthritis Research & Therapy
|September 10, 2015
PubMed
Abstract

Insights

Genetic variants in Interleukin-2 receptor-α (IL2RA)-rs2104286 and soluble IL2Rα levels are associated with rheumatoid arthritis (RA) persistence. This finding highlights IL2RA

Area of Science:

  • Immunogenetics
  • Rheumatology

Background:

  • Rheumatoid arthritis (RA) is typically a chronic condition, but some patients achieve sustained remission off disease-modifying antirheumatic drugs (DMARDs).
  • Understanding the mechanisms behind RA persistence is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate genetic variants associated with DMARD-free sustained remission in rheumatoid arthritis.
  • To explore the relationship between genetic predisposition to radiographic progression and sustained remission.

Main Methods:

  • A candidate gene study was conducted on 645 Dutch RA patients, analyzing variants previously linked to radiographic progression.
  • Cox-regression analyses and Bonferroni correction were applied, with soluble IL2Rα levels also assessed.
  • Replication was performed in the French ESPOIR cohort, and results were combined via meta-analysis.

Main Results:

  • The Human Leukocyte Antigens (HLA)-DRB1-shared epitope (SE) alleles were associated with reduced remission.
  • The IL2RA-rs2104286 minor allele was linked to an increased chance of remission and lower soluble IL2Rα (sIL2Rα) levels.
  • Lower sIL2Rα levels also correlated with a higher likelihood of remission, with both IL2RA-rs2104286 and sIL2Rα levels independently associated with RA persistence.

Conclusions:

  • IL2RA-rs2104286 and sIL2Rα levels are associated with rheumatoid arthritis persistence.
  • IL2RA variants demonstrate protective effects against RA, multiple sclerosis, and diabetes mellitus.
  • IL2RA-rs2104286 is a significant genetic variant linked to both joint destruction and RA persistence, underscoring IL2RA's role in RA pathogenesis.

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