Abstract TP245: Identifying Ischemic Stroke Etiology Through Cytokine Biomarkers

Abstract

Background: Ischemic stroke can arise from various etiologies, such as cardioembolism, atherosclerosis, small vessel disease or cryptogenic. Accurate identification of stroke etiology is vital for secondary stroke prevention. Accumulating evidence suggests that an imbalance of neuroprotective and neuroinflammatory cytokines may contribute to stroke outcomes. Interleukin-2 receptor subunit α (IL-2Rα), a cell surface protein that regulates lymphocyte activation, has been shown to have either pro-atherosclerotic or atheroprotective roles through activation of lymphocytes or regulatory T cells, respectively. We hypothesized that distinct cytokine profiles, and in particular IL-2Rα, may correlate with specific stroke etiology. Methods: Plasma samples were collected from patients with ischemic stroke that were admitted to Memorial Hermann Hospital, Houston by UTHealth biobank. ELISA was used to analyze the plasma samples for levels of IL-2Rα. The relationship between stroke etiology (TOAST criteria) and IL-2Rα was assessed using ANOVA and then adjusted for co-morbidities using multilinear regression models. Results: The mean age of patients was 63.4 years, 35.2% were women, 87% had hypertension, 48.1% had diabetes mellitus, and 53.7% had hyperlipidemia. IL-2Rα levels were significantly elevated in patients with ischemic stroke due to large-artery atherosclerosis (53.5±4.7 pg/ml) as compared to cardioembolic (35.6±6.5 pg/ml), small vessel disease (38.2±7.4pg/ml) or cryptogenic etiology 32±7.8; p<0.01). Conclusions: Our study suggests that IL-2Rα is significantly elevated in ischemic strokes caused by atherosclerosis compared to other ischemic etiologies. This suggests the role of lymphocytic activation in strokes from intracranial and extracranial atherosclerotic disease, which may be used as a therapeutic target. It also identifies a novel biomarker for ischemic strokes from atherosclerosis. Future studies identifying the upstream and downstream pathways that lead to IL-2Rα activation and stroke in atherosclerotic lesions, will further add to our understanding of the characteristics of atherosclerotic lesions that lead to ischemic strokes.