Abstract TP96: A Genomic Profile of Immune Mediated Mechanisms Associated with Stroke Recovery.
Objective: We recently identified a profile of genomic biomarkers related to the inflammatory and immune signaling mechanisms in human ischemic stroke. The objective of this study was to identify novel biomarkers for ischemic stroke recovery through gene expression profiling and pathway analysis.
Methods: Peripheral whole blood samples were collected from n=34 MRI diagnosed ischemic stroke patients’ ≥18 years of age at two time points: within 24 hours from stroke symptom onset and 24-48 hours later. Modified rankin scale (MRS) was used to determine 30 day stroke outcome. Total RNA was extracted from whole blood stabilized in Paxgene RNA tubes, amplified, and hybridized to Illumina HumanRef-8v2 bead chips. Gene expression was compared in a univariate manner between stroke patients at both time points and good versus bad outcome using t-test in GeneSpring. Inflation of type one error was corrected by Bonferroni and Ingenuity Systems Pathway analysis (IPA) was performed. A validation cohort of ischemic stroke patients was recruited from WVU Ruby Memorial Hospital (WVUH).
Results: Three genes were significantly downregulated over time (LY96, IL8, and SDPR) ( Bonferroni corrected p<0.05) Pathway analysis revealed cytotoxic t-lymphocyte antigen 4 (CTLA4) and dopamine signaling as highly significant canonical pathways present in the peripheral whole blood of ischemic stroke patients 24-48 post onset of symptoms. When controlling for age and hypertension, high baseline expression of ARG1, MMP9, TLR2 and TLR4 significantly predicted worse scores on the MRS. Validation in a separate cohort of subjects at WVUH confirms these findings.
Conclusions: In this study we have demonstrated that ischemic injury to the brain produces an immune response that can be observed in the peripheral blood following stroke. Markers of immune dysfunction in the early post-stroke phase, such as arginase, TLR signaling and T-cell activity may prove useful for identifying patients with increased risk of post-stroke immune suppression and poor recovery.
- © 2012 by American Heart Association, Inc.