title: Type I interferons are associated with subclinical markers of cardiovascular disease in a cohort of systemic lupus erythematosus patients.
abstract: BACKGROUND
  Systemic lupus erythematosus (SLE) patients have a striking increase in cardiovascular (CV) comorbidity not fully explained by the Framingham risk score. Recent evidence from in vitro studies suggests that type I interferons (IFN) could promote premature CV disease (CVD) in SLE. We assessed the association of type I IFN signatures with functional and anatomical evidence of vascular damage, and with biomarkers of CV risk in a cohort of lupus patients without overt CVD.
  
  
  RESULTS
  Serum type I IFN activity (induction of five IFN-inducible genes; IFIGs) from 95 SLE patient and 38 controls was quantified by real-time PCR. Flow mediated dilatation (FMD) of the brachial artery and carotid intima media thickness (CIMT) were quantified by ultrasound, and coronary calcification by computed tomography. Serum vascular biomarkers were measured by ELISA. We evaluated the effect of type I IFNs on FMD, CIMT and coronary calcification by first applying principal components analysis to combine data from five IFIGs into summary components that could be simultaneously modeled. Three components were derived explaining 97.1% of the total IFIG variation. Multivariable linear regression was utilized to investigate the association between the three components and other covariates, with the outcomes of FMD and CIMT; zero-inflated Poisson regression was used for modeling of coronary calcification. After controlling for traditional CV risk factors, enhanced serum IFN activity was significantly associated with decreased endothelial function in SLE patients and controls (p<0.05 for component 3), increased CIMT among SLE patients (p<0.01 for components 1 and 2), and severity of coronary calcification among SLE patients (p<0.001 for component 3).
  
  
  CONCLUSIONS
  Type I IFNs are independently associated with atherosclerosis development in lupus patients without history of overt CVD and after controlling for Framingham risk factors. This study further supports the hypothesis that type I IFNs promote premature vascular damage in SLE.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Somers
authors.forename: Wenpu
authors.initials: W
authors.lastname: Zhao
authors.forename: Emily E
authors.initials: EE
authors.lastname: Lewis
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Wing
authors.forename: Baskaran
authors.initials: B
authors.lastname: Sundaram
authors.forename: Ella A
authors.initials: EA
authors.lastname: Kazerooni
authors.forename: W Joseph
authors.initials: WJ
authors.lastname: McCune
authors.forename: Mariana J
authors.initials: MJ
authors.lastname: Kaplan
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000150:complications* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012307:Risk Factors; D061205:Vascular Calcification / Q000175:diagnosis / Q000209:etiology
chemical_list: D015415:Biomarkers; D007370:Interferon Type I