title: Erythroid-specific transcriptional changes in PBMCs from pulmonary hypertension patients.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. ccheadl1@jhmi.edu
authors.forename: Chris
authors.initials: C
authors.lastname: Cheadle
authors.forename: Alan E
authors.initials: AE
authors.lastname: Berger
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Mathai
authors.forename: Dmitry N
authors.initials: DN
authors.lastname: Grigoryev
authors.forename: Tonya N
authors.initials: TN
authors.lastname: Watkins
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Sugawara
authors.forename: Sangjucta
authors.initials: S
authors.lastname: Barkataki
authors.forename: Jinshui
authors.initials: J
authors.lastname: Fan
authors.forename: Meher
authors.initials: M
authors.lastname: Boorgula
authors.forename: Laura
authors.initials: L
authors.lastname: Hummers
authors.forename: Ari L
authors.initials: AL
authors.lastname: Zaiman
authors.forename: Reda
authors.initials: R
authors.lastname: Girgis
authors.forename: Michael A
authors.initials: MA
authors.lastname: McDevitt
authors.forename: Roger A
authors.initials: RA
authors.lastname: Johns
authors.forename: Frederick
authors.initials: F
authors.lastname: Wigley
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Barnes
authors.forename: Paul M
authors.initials: PM
authors.lastname: Hassoun
mesh_terms: D000328:Adult; D000368:Aged; D041905:Erythroid Cells / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000503:physiopathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D059467:Transcriptome