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


RESULTS
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
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.
Pendergrass
Sarah A
SA
Department of Genetics, Dartmouth Medical School, Hanover, New Hampshire, United States of America.
Hayes
Everett
E
Farina
Giuseppina
G
Lemaire
Raphael
R
Farber
Harrison W
HW
Whitfield
Michael L
ML
Lafyatis
Robert
R
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001808:Blood Vessels / Q000293:injuries* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000150:complications* / Q000378:metabolism*; D007249:Inflammation / Q000097:blood / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011651:Pulmonary Artery; D012595:Scleroderma, Systemic / Q000097:blood / Q000150:complications* / Q000378:metabolism*
D015415:Biomarkers
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