Abstract T MP50: Novel TIA Serum Biomarkers Identified by Mass-Spectroscopy Proteomics

Abstract

Background: One of the “holy grails” in vascular neurology is a TIA serum marker. Mass spectrometry-based proteomics, a unique, unbiased method to identify candidate proteins, was used to test the serum of patients with transient neurologic symptoms for biomarkers of cerebral ischemia. Methods: Patients with transient neurologic symptoms were prospectively enrolled. Mass spectrometry was performed on the serum samples, and results were searched against the Human Uniport database. Three candidate proteins were found, and serum concentrations of these proteins were measured by ELISA in a second cohort of prospectively enrolled patients. The student’s t-test was used for comparison. The Benjamini-Hochberg false discovery rate controlling procedure for multiple comparison adjustments determined significance for the proteomic screen. Results: Patients with TIA (n=20), minor stroke (n=15), and controls (i.e. migraine, seizure, n=12) were enrolled in the first cohort. Ceruloplasmin, complement component C8 gamma (C8γ) and platelet basic protein (PBP) were significantly different between the ischemic samples (TIA and minor stroke) and the controls (p = 0.0001, p=0.00027, p=0.00105 respectively). A second cohort of patients with TIA (n=16), minor stroke (n=20), and controls’ (n=12) serum was tested. PBP serum concentrations were increased in the ischemic samples compared to control (for TIA and stroke, p= 0.04, for TIA alone, p=0.027). Ceruloplasmin trended towards increased concentrations in the ischemic groups (p=0.10), and an insignificant increase in C8γ (p=0.23) was found. Conclusions: PBP has been identified as potential serum biomarker for TIA. Larger sample size may find that ceruloplasmin is an additional candidate. Ultimately, a panel of proteins may be required. Larger studies are needed to determine the validity of these proteins in clinical use.