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Limited Systemic Sclerosis Patients with Pulmonary Arterial Hypertension Show Biomarkers of Inflammation and Vascular Injury

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  • Sarah A Pendergrass
  • Everett Hayes
  • Giuseppina Farina
  • Raphael Lemaire
  • Harrison W Farber
  • Michael L Whitfield
  • Robert Lafyatis

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. Methods and Findings: 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 and Significance: 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.

Suggested Citation

  • Sarah A Pendergrass & Everett Hayes & Giuseppina Farina & Raphael Lemaire & Harrison W Farber & Michael L Whitfield & Robert Lafyatis, 2010. "Limited Systemic Sclerosis Patients with Pulmonary Arterial Hypertension Show Biomarkers of Inflammation and Vascular Injury," PLOS ONE, Public Library of Science, vol. 5(8), pages 1-13, August.
    • Handle: RePEc:plo:pone00:0012106
    DOI: 10.1371/journal.pone.0012106
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    References listed on IDEAS

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    1. Liu, Yufeng & Hayes, David Neil & Nobel, Andrew & Marron, J. S, 2008. "Statistical Significance of Clustering for High-Dimension, Low–Sample Size Data," Journal of the American Statistical Association, American Statistical Association, vol. 103(483), pages 1281-1293.
    2. Ausra Milano & Sarah A Pendergrass & Jennifer L Sargent & Lacy K George & Timothy H McCalmont & M Kari Connolly & Michael L Whitfield, 2008. "Molecular Subsets in the Gene Expression Signatures of Scleroderma Skin," PLOS ONE, Public Library of Science, vol. 3(7), pages 1-19, July.
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