IFNα Serum Levels Are Associated With Endothelial Progenitor Cells Imbalance and Disease Features in Rheumatoid Arthritis Patients

PLoS One. 2014 Jan 21;9(1):e86069. doi: 10.1371/journal.pone.0086069. eCollection 2014.

Abstract

Introduction: IFNα has been largely implicated in the ethiopathogenesis of autoimmune diseases but only recently it has been linked to endothelial damage and accelerated atherosclerosis in autoimmunity. In addition, proinflammatory conditions are supposed to be implicated in the cardiovascular status of these patients. Since a role for IFNα in endothelial damage and impaired Endothelial Progenitor Cell (EPC) number and function has been reported in other diseases, we aimed to evaluate the potential associations of IFNα serum levels on EPC populations and cytokine profiles in Rheumatoid Arthritis (RA) patients.

Methods: pre-EPC, EPC and mature EPC (mEPC) populations were quantified by flow cytometry analyzing their differential CD34, CD133 and VEGFR2 expression in blood samples from 120 RA patients, 52 healthy controls (HC), and 83 systemic lupus erythematosus (SLE) patients as disease control. Cytokine serum levels were measured by immunoassays and clinical and immunological data, including cardiovascular (CV) events and CV risk factors, were retrospectively obtained by reviewing clinical records.

Results: Long-standing, but not recent onset RA patients displayed a significant depletion of all endothelial progenitor populations, unless high IFNα levels were present. In fact, the IFN(high) RA patient group (n = 40, 33%), showed increased EPC levels, comparable to SLE patients. In addition, high IFNα serum levels were associated with higher disease activity (DAS28), presence of autoantibodies, higher levels of IL-1β, IL-6, IL-10 and MIP-1α, lower amounts of TGF-β, and increased mEPC/EPC ratio, thus suggesting higher rates of endothelial damage and an endothelial repair failure. Finally, the relationship between high IFNα levels and occurrence of CV events observed in RA patients seems to support this hypothesis.

Conclusions: IFNα serum marker could be used to identify a group of RA patients with increased disease activity, EPC imbalance, enhanced proinflammatory profile and higher cardiovascular risk, probably due, at least in part, to an impaired endothelial repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / pathology*
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / pathology
  • Cell Movement
  • Demography
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Female
  • Flow Cytometry
  • Humans
  • Interferon-alpha / blood*
  • Male
  • Middle Aged
  • Stem Cells / metabolism*
  • Stem Cells / pathology

Substances

  • Interferon-alpha

Grant support

This work was supported by European Union FEDER funds and the Fondo de Investigación Sanitaria (FIS, PI08/0570 and PI12/0053). JRC is a recipient of a FPU grant from the Ministerio de Educación. CP was supported by a fellowship from FIS and BdP was supported by a fellowship from FICYT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.