Abstract P512: Immune Correlates of Functional Outcome in Acute Ischemic Stroke (AIS) Patients

Abstract

Introduction: Acute Ischemic Stroke (AIS) is one of the leading causes of disability and death in US. Although Endovascular Therapy (EVT) remains the mainstay therapy during acute phase for large vessel occlusions (LVOs), functional outcome varies among the treated patients. This ischemic injury results in an inflammatory response which plays an important role in the functional and neurological outcomes. We hypothesize that the early changes in the inflammatory response near the site of occlusion can be used as predictor of long-term neurofunctional decline Methods: AIS-LVO patients presenting to an academic comprehensive stroke center (CSC) within 24 hours from their last known well and undergoing EVT were included. Blood was collected proximal and distal to the thrombus during thrombectomy. Control samples were collected from the femoral artery and median cubital vein. Cytokine analysis and deep immune profiling was performed using a 20-parameter bead array and 13-parameter flow cytometer. Least Absolute Shrinkage and Selection Operator (LASSO) models were used for cell selection and correlation was evaluated for outcomes including mRS, NIHSS, MOCA and mortality, using R-software. Results: With 19 patients meeting the inclusion criteria, cytokine analysis revealed a significant increase in MMP and IFN-g, and decrease in GM-CSF, IL17, TNF-α, IL6, MIP-1a, and MIP-1b distal to clot. Flow cytometry analysis revealed a significant decrease in NK-T-cells, and CD8 T-cells counts and a relative increase in GM-CSF+ and IL17+ CD4 T-cells distal to clot. Immunological and neurological analysis revealed a correlation with CD4 + IFN-γ - IL10 + (r=0.7) & CD8 + IFN-γ - GMCSF + (0.6) with mRS, and CD4 + IFN-γ - IL10 + (r=0.7), CD4+ IFN-γ - IL17 + (r= -0.6), & CD8 + IFN-γ + IL17 + (r=0.7) cells with mortality. Conclusion: Our results indicate that local ischemia results in a hyperacute adaptive immune response at the site of occlusion. This immune response is predictive of functional outcome among AIS patients and is impactful in multiple ways, including the use of supportive therapy for patients with a poor functional trajectory and the use of immune-modulators at the site of ischemic injury.