title: Type I interferon as a novel risk factor for endothelial progenitor cell depletion and endothelial dysfunction in systemic lupus erythematosus.
abstract: OBJECTIVE
  The premature atherosclerosis seen in patients with systemic lupus erythematosus (SLE) is not explained by traditional risk factors. SLE disease activity, such as renal involvement and presence of autoantibodies, is associated with elevated serum levels of type I interferon (IFN-I), a family of cytokines with potent antiviral and antiproliferative effects. This study was undertaken to test the hypothesis that elevated IFN-I levels could lead to endothelial dysfunction, a surrogate for cardiovascular disease, by causing a reduction in the number of endothelial progenitor cells (EPCs), bone marrow-derived cells that participate in endothelial repair.
  
  
  METHODS
  EPCs were enumerated in the peripheral blood of SLE patients (n = 70) and healthy controls (n = 31), using a colony-forming assay. Serum IFN-I levels were quantified by real-time polymerase chain reaction measurement of the expression of the IFN-I-inducible gene MX1. Endothelial function was determined by peripheral arterial plethysmography.
  
  
  RESULTS
  SLE patients had markedly reduced levels of EPC colony-forming units compared with controls (median 5.7/ml peripheral blood [interquartile range 1.9-12.8] versus 28.5/ml peripheral blood [14.7-47.3]; P < 0.0001), and the depletion of EPCs was more dramatic in patients with elevated levels of IFN-I. Stepwise multiple regression analysis showed that MX1 expression and serum levels of C-reactive protein were independently associated with the reduction of EPCs. Importantly, high IFN-I levels were associated with impaired endothelial function in patients with SLE.
  
  
  CONCLUSIONS
  These data support the novel hypothesis that depletion of EPCs caused by excessive IFN-I may be linked to endothelial dysfunction and increased cardiovascular risk in SLE.
authors.affiliation: University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: Pui Y
authors.initials: PY
authors.lastname: Lee
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Hanno B
authors.initials: HB
authors.lastname: Richards
authors.forename: Fay S
authors.initials: FS
authors.lastname: Chan
authors.forename: Haoyang
authors.initials: H
authors.lastname: Zhuang
authors.forename: Sonali
authors.initials: S
authors.lastname: Narain
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Butfiloski
authors.forename: Eric S
authors.initials: ES
authors.lastname: Sobel
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
authors.forename: Mark S
authors.initials: MS
authors.lastname: Segal
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000097:blood* / Q000453:epidemiology* / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000097:blood*; D016899:Interferon-beta / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000453:epidemiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013234:Stem Cells / Q000473:pathology; D015854:Up-Regulation
chemical_list: D016898:Interferon-alpha; D016899:Interferon-beta; D002097:C-Reactive Protein