O-015 What Can Systemic and Intracranial Proteomic Profiles Tell Us about Why Some TICI 3 Patients Do Better Than Others?

Introduction In 2003, Higashida et al. proposed the Thrombolysis in Cerebral Infarction (TICI) scale to standardize grading of angiographic outcomes after ischemic stroke intervention. Grades 0–3 represent a spectrum from no perfusion to complete perfusion and are routinely documented after mechanical thrombectomy (MT). Although a TICI score of 3 is the best angiographic outcome, not all TICI 3 patients have remarkable outcomes. The objective of this study is to investigate intracranial and systemic proteomic profiles of TICI 3 subjects in relation to their National Institute of Health Stroke Scale/Score (NIHSS) and modified Rankin Score (mRS) at time of discharge. Methods The Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC) is a continually enrolling tissue bank (clinicaltrials.gov NCT03153683) from emergent large vessel occlusion (ELVO) stroke patients undergoing MT. Systemic and intracranial plasma samples from N=32 TICI 3 patients were analyzed for proteomic expression by Olink Proteomics. Proteomic expression was assessed in relation to both NIHSS and mRS scores at discharge. Statistical analyses included t-tests and linear regressions. Results Linear regression analysis revealed 23 systemic proteins and 8 intracranial proteins found to be significantly related to NIHSS at discharge. Linear regression analysis also revealed 23 systemic proteins and 8 intracranial proteins found to be significantly related to mRS at discharge. From these regressions, six proteins were identified that demonstrated a significant relationship with both NIHSS and mRS from both systemic and intracranial samples. These proteins include signaling lymphocytic activation molecule (SLAMF1), C-C motif chemokine 20 (CCL20), CUB domain-containing protein 1 (CDCP1), Ig lambda-2 chain C regions (IGLC2), interleukin 6 (IL-6), and interleukin-12 subunit beta (IL-12β). All proteins (both intracranial and systemic) were positively correlated with both outcome scores (p-values < 0.05) indicating higher proteomic expression related to worse NIHSS and mRS scores. Discussion From an angiographic standpoint, TICI 3 reperfusion is optimal; however, not all subjects with full reperfusion do well following MT. Our study reports novel data on the intracranial and systemic proteomic profiles of TICI 3 subjects in relation to their discharge NIHSS and mRS scores. High levels of IL-6 have been previously shown to predict poorer outcome in ischemic stroke, including worse infarct volume and the consequential upregulation of downstream neuroinflammatory cascades. Our findings corroborate previous findings and provide novel data suggesting IL-6 also influences poorer outcomes within a subset of TICI 3 subjects. Previous studies have suggested the protein SLAMF1 as a potential therapeutic target for inflammatory and autoimmune diseases. Gene expression experiments have shown SLAM1 to be downregulated in ischemic stroke, however, in our cohort of TICI 3 thrombectomized patients, we found higher SLAM1 levels were positively correlated with worse functional outcome measures. In conclusion, intracranial and systemic proteomic differences in TICI 3 subjects may inform why some outcomes are superior to others. Preliminary data presented here provide a springboard for further investigation into how proteins may serve as prognostic biomarkers or therapeutic targets in a subset of MT subjects. Disclosures B. Maglinger: None. J. Frank: None. L. Sheikhi: None. S. Pahwa: None. D. Dornbos: None. C. Rupareliya: None. C. McLouth: None. A. Trout: None. J. Turchan-Cholewo: None. A. Stowe: 4; C; Cerelux, LLC. J. Fraser: 1; C; AHA. 2; C; Penumbra, Medtronic, Stream Biomedical. 4; C; Fawkes Biotechnology; Cerelux, LLC. K. Pennypacker: 4; C; Cerelux, LLC.