IL-33 and soluble ST2 levels as novel predictors for remission and progression of carotid plaque in early rheumatoid arthritis: A prospective study

Semin Arthritis Rheum. 2015 Aug;45(1):18-27. doi: 10.1016/j.semarthrit.2015.02.001. Epub 2015 Feb 20.

Abstract

Objectives: To study the association between the baseline IL-33 and soluble ST2 (sST2) levels with disease remission and progression of carotid atherosclerosis in early rheumatoid arthritis (ERA) patients.

Methods: A total of 98 ERA patients were enrolled. Disease activity and the presence of carotid plaque were evaluated at baseline and 12 months later. Plasma IL-33 and sST2 levels were determined using enzyme-linked immunosorbent assay kits.

Results: Baseline IL-33 and sST2 levels were associated with inflammatory markers and cardiovascular (CV) risk factors. Overall, 44(45%), 18(18%), and 21(21%) patients achieved remission based on 28-joint disease activity score (DAS28), Boolean, and simplified disease activity score (SDAI) criteria at 12 months, respectively. Patients with detectable IL-33 at baseline were less likely to achieve DAS28 (P = 0.010) and SDAI remission (P = 0.021), while a lower baseline sST2 level was able to predict DAS28, Boolean, and SDAI remission (P = 0.005, 0.001, and <0.001, respectively). Using multivariate analysis, a lower baseline sST2 level independently predict Boolean (OR = 0.789; P = 0.005) and SDAI remission (0.812; P = 0.008). Regarding carotid atherosclerosis, 9/98(9.2%) patients had plaque progression at 12 months. Baseline IL-33 was detectable in 8/9(89%) and 42/83(51%) of patients with and without plaque progression respectively (P = 0.029). Baseline detectable IL-33 was an independent predictor for plaque progression after adjusting for traditional CV risk factors (P = 0.017).

Conclusions: Lower baseline sST2 levels independently predict disease remission and baseline detectable IL-33 independently predicts carotid plaque progression in ERA patients. This study suggests that inflammation induced by the IL-33/ST2 axis may play a significant role in the development of cardiovascular disease in RA.

Keywords: Atherosclerosis; Carotid plaque; Disease remission; Early rheumatoid arthritis; IL-33; Soluble ST2.

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / drug therapy
  • Carotid Artery Diseases / blood
  • Carotid Artery Diseases / complications
  • Carotid Artery Diseases / diagnosis*
  • Disease Progression
  • Female
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33 / blood*
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic / blood
  • Plaque, Atherosclerotic / complications
  • Plaque, Atherosclerotic / diagnosis*
  • Prospective Studies
  • Receptors, Cell Surface / blood*
  • Remission Induction
  • Severity of Illness Index

Substances

  • Antirheumatic Agents
  • IL1RL1 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Receptors, Cell Surface