RGD Reference Report - Limited systemic sclerosis patients with pulmonary arterial hypertension show biomarkers of inflammation and vascular injury. - Rat Genome Database

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Limited systemic sclerosis patients with pulmonary arterial hypertension show biomarkers of inflammation and vascular injury.

Authors: Pendergrass, SA  Hayes, E  Farina, G  Lemaire, R  Farber, HW  Whitfield, ML  Lafyatis, R 
Citation: Pendergrass SA, etal., PLoS One. 2010 Aug 17;5(8):e12106.
RGD ID: 4892610
Pubmed: (View Article at PubMed) PMID:20808962
DOI: Full-text: DOI:10.1371/journal.pone.0012106

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.



Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Ifngr1  (interferon gamma receptor 1)
Il13ra1  (interleukin 13 receptor subunit alpha 1)
Il1b  (interleukin 1 beta)
Jak2  (Janus kinase 2)

Genes (Mus musculus)
Ifngr1  (interferon gamma receptor 1)
Il13ra1  (interleukin 13 receptor, alpha 1)
Il1b  (interleukin 1 beta)
Jak2  (Janus kinase 2)

Genes (Homo sapiens)
IFNGR1  (interferon gamma receptor 1)
IL13RA1  (interleukin 13 receptor subunit alpha 1)
IL1B  (interleukin 1 beta)
JAK2  (Janus kinase 2)


Additional Information