title: Dysfunction of endothelial progenitor cells is associated with the type I IFN pathway in patients with polymyositis and dermatomyositis.
abstract: Alterations in phenotype and function of endothelial progenitor cells (EPCs) have been associated with poor vascular outcomes and impaired vascular repair in various conditions. Our hypothesis was that patients with PM and DM have dysregulation of EPCs driven by type I IFN and IL-18 similar to other autoimmune diseases.
  
  
  
  Quantification of circulating EPCs was performed by flow cytometry in patients with PM/DM and matched healthy controls. The ability of EPCs to differentiate into mature endothelial cells was investigated by light and fluorescence microscopy quantification in the presence or absence of PM/DM or control serum, neutralizing antibodies to type I IFN receptor or IL-18. Serum type I IFN activity was quantified by induction of type I IFN-inducible genes in HeLa cells. Circulating IL-18 concentrations were assessed by ELISA.
  
  
  
  Circulating EPCs were significantly lower in PM/DM patients compared with controls. PM/DM EPCs displayed a decreased capacity to differentiate into mature endothelial cells and PM/DM serum significantly inhibited differentiation of control EPCs. This effect was reversed in the majority of samples with neutralizing antibodies to IL-18 or to type I IFN receptor or by a combination of these antibodies. Patients with associated impairments in EPC function had higher type I IFN serum activity.
  
  
  
  PM/DM is associated with dysregulation of EPC phenotype and function that may be attributed, at least in part, to aberrant IL-18 and type I IFN pathways. The implication of these vasculopathic findings for disease prognosis and complications remains to be determined.
authors: Department of Medicine, Rheumatology Unit, Karolinska University Hospital, Karolinska Institutet, Solna, Sweden louise.ekholm@karolinska.se.
authors: Louise
authors: L
authors: Ekholm
authors: Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI.
authors: J Michelle
authors: JM
authors: Kahlenberg
authors: Department of Medicine, Rheumatology Unit, Karolinska University Hospital, Karolinska Institutet, Solna, Sweden.
authors: Sevim
authors: S
authors: Barbasso Helmers
authors: Department of Medicine, Rheumatology Unit, Karolinska University Hospital, Karolinska Institutet, Solna, Sweden.
authors: Anna
authors: A
authors: Tjärnlund
authors: Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI.
authors: Srilakshmi
authors: S
authors: Yalavarthi
authors: Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, NIH, Bethesda, MD, USA.
authors: Wenpu
authors: W
authors: Zhao
authors: Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, NIH, Bethesda, MD, USA.
authors: Nickie
authors: N
authors: Seto
authors: Pharmacy and Pharmacology, University of Bath, Bath, UK.
authors: Zoe
authors: Z
authors: Betteridge
authors: Department of Medicine, Rheumatology Unit, Karolinska University Hospital, Karolinska Institutet, Solna, Sweden.
authors: Ingrid E
authors: IE
authors: Lundberg
authors: Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, NIH, Bethesda, MD, USA.
authors: Mariana J
authors: MJ
authors: Kaplan
mesh_terms: D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000502:physiology; D003882:Dermatomyositis / Q000378:metabolism / Q000473:pathology*; D066026:Endothelial Progenitor Cells / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017285:Polymyositis / Q000378:metabolism / Q000473:pathology*; D011446:Prospective Studies; D053633:Receptor, Interferon alpha-beta / Q000378:metabolism
chemical_list: D007370:Interferon Type I; D020382:Interleukin-18; D053633:Receptor, Interferon alpha-beta
keywords: IFN-regulated gene expression; IL-18; autoantibodies; idiopathic inflammatory myopathies; interferon signature