Altered immune phenotype in peripheral blood cells of patients with scleroderma-associated pulmonary hypertension

Michael G. Risbano, Christina A. Meadows, Christopher D. Coldren, Tiffany J. Jenkins, Michael G. Edwards, David Collier, Wendy Huber, Douglas G. Mack, Andrew P. Fontenot, Mark W. Geraci, Todd M. Bull

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Pulmonary arterial hypertension is a common and fatal complication of scleroderma that may involve inflammatory and autoimmune mechanisms. Alterations in the gene expression of peripheral blood mononuclear cells have been previously described in patients with pulmonary arterial hypertension. Our goal is to identify differentially expressed genes in peripheral blood mononuclear cells in scleroderma patients with and without pulmonary hypertension as biomarkers of disease. Gene expression analysis was performed on a Microarray Cohort of scleroderma patients with (n= 10) and without (n= 10) pulmonary hypertension. Differentially expressed genes were confirmed in the Microarray Cohort and validated in a Validation Cohort of scleroderma patients with (n= 15) and without (n= 19) pulmonary hypertension by RT-qPCR. We identified inflammatory and immune-related genes including interleukin-7 receptor (IL-7R) and chemokine receptor 7 as differentially expressed in patients with scleroderma-associated pulmonary hypertension. Flow cytometry confirmed decreased expression of IL-7R on circulating CD4+ T-cells from scleroderma patients with pulmonary hypertension. Differences exist in the expression of inflammatory and immune-related genes in peripheral blood cells from patients with scleroderma-related pulmonary hypertension compared to those with normal pulmonary artery pressures. These findings may have implications as biomarkers to screen at-risk populations for early diagnosis and provide insight into mechanisms of scleroderma-related pulmonary hypertension.

Original languageEnglish (US)
Pages (from-to)210-218
Number of pages9
JournalClinical and translational science
Volume3
Issue number5
DOIs
StatePublished - Oct 2010

Keywords

  • Gene array
  • Gene expression
  • Inflammation
  • Interleukins
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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