Using Peripheral Blood Mononuclear Cells to Determine a Gene Expression Profile of Acute Ischemic Stroke

Abstract

Background-Direct brain biopsy is rarely indicated during acute stroke. This study uses peripheral blood mononuclear cells (PBMCs) to determine whether a systemic gene expression profile could be demonstrated in patients with acute ischemic stroke. Methods and Results-Using oligonucleotide microarrays, we compared the gene expression profile of an index cohort of 20 patients with confirmed ischemic stroke on neuroimaging studies with that of 20 referent subjects. Validation studies used quantitative real-time polymerase chain reaction to measure the levels of 9 upregulated genes in the index cohort, and an independent cohort of 9 patients and 10 referent subjects was prospectively studied to determine the accuracy of the Prediction Analysis for Microarrays list to classify stroke. After correction for multiple comparisons with the Bonferroni technique, 190 genes were significantly different between the stroke and referent groups. Broad classes of genes included white blood cell activation and differentiation (Ϸ60%), genes associated with hypoxia and vascular repair, and genes potentially associated with an altered cerebral microenvironment. Real-time polymerase chain reaction confirmed increased mRNA expression in 9 of 9 upregulated stroke-associated genes in the index cohort. A panel of 22 genes derived from the Prediction Analysis for Microarrays algorithm in the index cohort classified stroke in the validation cohort with a sensitivity of 78% and a specificity of 80%.

Blood Biomarkers of Ischemic Stroke

“…RNA isolated from blood mononuclear cells identified 190 genes differentially expressed in ischemic stroke compared to controls. A 22 gene panel of the 190 genes was able to distinguished ischemic stroke from controls with 78% sensitivity and 80% specificity [26]. A subsequent study of whole blood RNA identified 1335 genes differentially expressed in acute ischemic stroke compared to controls [27].…”

Gene Expression in Blood Changes Rapidly in Neutrophils and Monocytes after Ischemic Stroke in Humans: A Microarray Study

“…In addition, there was a common blood gene expression profile that correlated with the occurrence of neuronal cell death regardless of the cause (Tang et al, 2003). This led to a recent human study by Moore et al (2005), who found a genomic signature from peripheral blood that was diagnostic for ischemic stroke in humans. This landmark study examined patients at roughly 1 to 4 days after ischemic stroke, and studied peripheral blood mononuclear cell (PBMC) gene expression.…”

Genomic Analysis of Circulating Cells: A Window Into Atherosclerosis

“…In another study, gene expression in blood MNCs from ischemic stroke and control subjects revealed a panel of genes with 78% sensitivity and 80% specificity at correctly identifying stroke subjects (Moore et al 2005). Though not all patients had documented atherosclerosis, coronary artery disease history and other cardiac risk factors were more prevalent in the group of elderly patients with stroke.…”

“…Though not all patients had documented atherosclerosis, coronary artery disease history and other cardiac risk factors were more prevalent in the group of elderly patients with stroke. In their list of stroke "classifier genes", the monocyte activation genes identified included FOS, DUSP1, CD14 and the scavenger receptor CD36 (Moore et al 2005, Patino et al 2005). …”