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PLoS By Category | Recent PLoS Articles
Immunology - Molecular Biology - Rheumatology

Erythroid-Specific Transcriptional Changes in PBMCs from Pulmonary Hypertension Patients
Published: Tuesday, April 24, 2012
Author: Chris Cheadle et al.

by Chris Cheadle, Alan E. Berger, Stephen C. Mathai, Dmitry N. Grigoryev, Tonya N. Watkins, Yumiko Sugawara, Sangjucta Barkataki, Jinshui Fan, Meher Boorgula, Laura Hummers, Ari L. Zaiman, Reda Girgis, Michael A. McDevitt, Roger A. Johns, Frederick Wigley, Kathleen C. Barnes, Paul M. Hassoun

Background

Gene expression profiling of peripheral blood mononuclear cells (PBMCs) is a powerful tool for the identification of surrogate markers involved in disease processes. The hypothesis tested in this study was that chronic exposure of PBMCs to a hypertensive environment in remodeled pulmonary vessels would be reflected by specific transcriptional changes in these cells.

Methodology/Principal Findings

The transcript profiles of PBMCs from 30 idiopathic pulmonary arterial hypertension patients (IPAH), 19 patients with systemic sclerosis without pulmonary hypertension (SSc), 42 scleroderma-associated pulmonary arterial hypertensio patients (SSc-PAH), and 8 patients with SSc complicated by interstitial lung disease and pulmonary hypertension (SSc-PH-ILD) were compared to the gene expression profiles of PBMCs from 41 healthy individuals. Multiple gene expression signatures were identified which could distinguish various disease groups from controls. One of these signatures, specific for erythrocyte maturation, is enriched specifically in patients with PH. This association was validated in multiple published datasets. The erythropoiesis signature was strongly correlated with hemodynamic measures of increasing disease severity in IPAH patients. No significant correlation of the same type was noted for SSc-PAH patients, this despite a clear signature enrichment within this group overall. These findings suggest an association of the erythropoiesis signature in PBMCs from patients with PH with a variable presentation among different subtypes of disease.

Conclusions/Significance

In PH, the expansion of immature red blood cell precursors may constitute a response to the increasingly hypoxic conditions prevalent in this syndrome. A correlation of this erythrocyte signature with more severe hypertension cases may provide an important biomarker of disease progression.

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