title: Limited systemic sclerosis patients with pulmonary arterial hypertension show biomarkers of inflammation and vascular injury.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is a common complication for individuals with limited systemic sclerosis (lSSc). The identification and characterization of biomarkers for lSSc-PAH should lead to less invasive screening, a better understanding of pathogenesis, and improved treatment.
  
  
  RESULTS
  Forty-nine PBMC samples were obtained from 21 lSSc subjects without PAH (lSSc-noPAH), 15 lSSc subjects with PAH (lSSc-PAH), and 10 healthy controls; three subjects provided PBMCs one year later. Genome-wide gene expression was measured for each sample. The levels of 89 cytokines were measured in serum from a subset of subjects by Multi-Analyte Profiling (MAP) immunoassays. Gene expression clearly distinguished lSSc samples from healthy controls, and separated lSSc-PAH from lSSc-NoPAH patients. Real-time quantitative PCR confirmed increased expression of 9 genes (ICAM1, IFNGR1, IL1B, IL13Ra1, JAK2, AIF1, CCR1, ALAS2, TIMP2) in lSSc-PAH patients. Increased circulating cytokine levels of inflammatory mediators such as TNF-alpha, IL1-beta, ICAM-1, and IL-6, and markers of vascular injury such as VCAM-1, VEGF, and von Willebrand Factor were found in lSSc-PAH subjects.
  
  
  CONCLUSIONS
  The gene expression and cytokine profiles of lSSc-PAH patients suggest the presence of activated monocytes, and show markers of vascular injury and inflammation. These genes and factors could serve as biomarkers of PAH involvement in lSSc.
authors.affiliation: Department of Genetics, Dartmouth Medical School, Hanover, New Hampshire, United States of America.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Pendergrass
authors.forename: Everett
authors.initials: E
authors.lastname: Hayes
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Farina
authors.forename: Raphael
authors.initials: R
authors.lastname: Lemaire
authors.forename: Harrison W
authors.initials: HW
authors.lastname: Farber
authors.forename: Michael L
authors.initials: ML
authors.lastname: Whitfield
authors.forename: Robert
authors.initials: R
authors.lastname: Lafyatis
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001808:Blood Vessels / Q000293:injuries* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000150:complications* / Q000378:metabolism*; D007249:Inflammation / Q000097:blood / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011651:Pulmonary Artery; D012595:Scleroderma, Systemic / Q000097:blood / Q000150:complications* / Q000378:metabolism*
chemical_list: D015415:Biomarkers
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