Altered immune phenotype in peripheral blood cells of patients with scleroderma-associated pulmonary hypertension.
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.
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, Aurora, USA. onabsir@gmail.com
Michael G
MG
Risbano
Christina A
CA
Meadows
Christopher D
CD
Coldren
Tiffany J
TJ
Jenkins
Michael G
MG
Edwards
David
D
Collier
Wendy
W
Huber
Douglas G
DG
Mack
Andrew P
AP
Fontenot
Mark W
MW
Geraci
Todd M
TM
Bull
D001773:Blood Cells / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016000:Cluster Analysis; D015331:Cohort Studies; D003710:Demography; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D005434:Flow Cytometry; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020395:Receptors, Interleukin-7 / Q000276:immunology; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012595:Scleroderma, Systemic / Q000097:blood* / Q000150:complications* / Q000235:genetics / Q000276:immunology
D020395:Receptors, Interleukin-7