Eastern Regional Meeting Abstracts

1 NOVEL BIOMARKERS OF STROKE PROGRESSION IDENTIFIED BY TEMPORAL QUANTITATIVE PROTEOMIC SCREENING MingMing Ning, Mary Lopez, Dave Sarracino, Michael Athenas, David McMullin, Ferdinando S. Buonanno, Eng H. Lo Neurology, Mass Gen Hosp/Harvard Med School, Boston, MA, United States. Purpose of Study: By quantitative proteomic screening of stroke patient plasma over time, we explore novel biomarkers of ischemic infarct progression to predict clinical outcomes and guide treatment decisions. Novel proteomic techniques help to simultaneously identify both known and unknown factors directly at the bedside. Methods Used: Plasma from acute ischemic stroke patients were isotope tagged and analysed on Obitrap MS. Patients were co-morbidity matched and blood sampled at 6h & 72h post stroke onset. All patients had worsened clinical outcome with increased infarct size and NIHSS over this time. Summary of Results: Pathway analysis of quantitative proteomic profiles suggests novel interaction of circulatory factors. Both established markers (S100) -important in cell injury and novel markers (TSP-4), important in cellular response and differentiation to injury are found to increase over time. As infarct size increased over 72 hours, a statistically significant decrease of matrix proteases such as ADAMTS-13 Y potentially interactive with elevated vWF was found. ADAMTS-13 deficiency correlate to increase clotting as it inactivates vWF by cleaving the bond between tyrosine and methionine in the A2 domain of vWF Y this coagulation pathway is important in acute stroke. Conclusions: Direct bedside proteomics is feasible as an initial step in understanding ischemic injury progression from the circulation. Quantitative analysis of protein-protein interactions with respect to clinical outcome revealed both an increased expression of relevant injurious markers, and a decrease of novel ‘‘protective’’ factors in disease-relevant pathways. Further validation of these novel biomarkers is ongoing.