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Interleukin 17 as a novel predictor of vascular function in rheumatoid arthritis
  1. Wendy Marder,
  2. Shokoufeh Khalatbari,
  3. James D Myles,
  4. Rita Hench,
  5. Srilakshmi Yalavarthi,
  6. Susan Lustig,
  7. Robert Brook,
  8. Mariana J Kaplan
  1. University of Michigan Medical School, Ann Arbor, Michigan, USA
  1. Correspondence to Mariana J Kaplan, Division of Rheumatology, University of Michigan Medical School, 5520 MSRBI, Box 5680, 1150 W. Medical Center Dr, Ann Arbor, MI 48109, USA; makaplan{at}


Background Rheumatoid arthritis (RA) is associated with enhanced cardiovascular (CV) risk and subclinical vascular disease. The proinflammatory milieu has been linked to premature atherosclerosis and endothelial dysfunction in RA. While interleukin 17 (IL-17) is considered pathogenic in RA, its role in determining vascular dysfunction in this disease has not been systematically assessed.

Objectives To analyse candidate variables that might determine endothelial function in various vascular territories in a cohort of patients with RA receiving treatment with biological agents, with minimal traditional CV risk factors and low disease activity score.

Methods Patients with RA (n=50) receiving stable treatment with biological agents underwent measurement of conduit artery endothelial function by brachial artery flow-mediated dilatation; arterial compliance by pulse wave velocity (PWV) assessment; and endothelium-dependent microvascular testing with Endo-Pat2000 device to assess the reactive hyperaemia index (RHI). IL-17 was quantified by ELISA and disease activity was assessed by 28-joint count Disease Activity Score.

Results IL-17 was the main determinant of lower RHI in univariate and multivariate analysis. Traditional and non-traditional CV risk variables determined PWV, with a signifi cant positive association with IL-17 in univariate and multivariate analysis. In contrast, conduit endothelial function was mainly determined by rheumatoid factor titres in univariate and multivariate analysis. Anti-cyclic citrullinated peptide titres, specific disease-modifying antirheumatic drugs or biological agents and disease activity did not determine vascular function.

Conclusion In patients with RA treated with biological agents, IL-17 is a main predictor of microvascular function and arterial compliance. This study suggests that IL-17 may play a significant role in development of endothelial dysfunction and cardiovascular disease in RA.

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  • Funding This work was supported by the National Institutes of Health through PHS grant RO1 HL086553 (to MJK) and UL1RR024986 (University of Michigan CTSA). WM was supported by K12HD001438 from the National Institutes of Health. This work was also supported in part by the Michigan Diabetes Research and Training Center, University of Michigan.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the University of Michigan institutional review board.

  • Provenance and peer review Not commissioned; externally peer reviewed.