Abstract TP113: Arginase-1 and S100a12 are Novel Candidates for the Study of Post Stroke Immune Suppression

Abstract

Objective: Stroke-induced immune suppression is common and clinically observed by the neutrophil- lymphocyte count ratio (NLR). The NLR can predict stroke recovery. The purpose of this study was to identify the relationships between the NLR and our previously established genomic profile for the characterization of immune pathways affecting stroke recovery. Methods: Patients with imaging confirmed ischemic stroke (IS) or transient ischemic attack (TIA) were recruited from West Virginia University Hospital (WVUH) in Morgantown, WV. White blood cell (WBC) differentials were performed on admission then analyzed as a ratio between the neutrophil and lymphocyte counts. Recovery was determined at 90 days for stroke patients only via the Modified Rankin Scale score (MRS). Peripheral blood samples were collected within 24 hours from symptom onset in Paxgene RNA tubes. Total RNA was extracted, amplified, and the expression of ARG1, CA4, CCR7, CSPG2, IQGAP, LY96, MMP9, ORM1, and S100a12 was quantified via Taqman PCR. The gene expression profile was compared to the NLR and MRS via Spearman rho correlation coefficient. Results: A total of 9 IS and 4 TIA patients were included in this study. The mean age of the IS patients was 72 years and TIA patients 70 years. Expression of ARG1 was significantly correlated with elevated NLR at baseline (r=.93, p=.001) for both IS and TIA and poor 90 day MRS (r=.86, p=.01) following IS. Elevated expression of S100A12 was correlated with higher neutrophil count (r=.67, p=.07) and total WBC (r= .78, p=.02) as well as with ARG1 expression (r=0.72; p=0.008) in both patient cohorts. Conclusion: We have identified a significant correlation between the expression of ARG1, S100a12 and the NLR for IS and TIA patients, as well as with ARG1 and outcome following IS. Elevated ARG1 decreases T-cell proliferation resulting in immune suppression. S100A12 modulates neutrophil activity. Our data suggests that ARG1 and S100A12 are interesting candidates for the study of the immune response following cerebral ischemia. Further studies are required to confirm this relationship when controlling for age, disease severity and comorbid conditions.