126 Intracranial Aneurysm Progression and Rupture States Correlate with Dynamic Aneurysmal Immune Landscape

INTRODUCTION: Intracranial aneurysms present a substantial public health challenge, with rupture resulting in poor morbidity and mortality outcomes. METHODS: Utilizing endoluminal sampling during IA treatment, we conducted proteomic analyses on samples of unruptured stable, unruptured growing, and ruptured IAs from 45 patients. After rigorous quality control, a subset of patient samples were retained for analysis, and analyzed via mass-cytometry-by-time-of-flight (cyTOF). We performed unbiased clustering techniques followed by applied machine learning algorithms to identify cell-cell interactions and enriched populations across the aneurysm subsets. RESULTS: Our proteomic analysis uncovered specific expression profiles within distinct aneurysm states, highlighting the dynamic shifts in immune cell populations across IA states. Ruptured IAs exhibited a pro-inflammatory immune cell polarization, whereas unruptured IAs showed variable expression of genes related to immune response, proliferation, and antigen presentation. Unbiased correlation analysis with multivariate logistic regression analysis revealed distinct immune signatures correlating significantly with aneurysm growth rate and state (p=0.002), emphasizing the role of immune profiling in understanding IA progression. Immune cell subsets were predictive of IA stability, with neutrophils predictive of ruptured and unruptured IAs, growing IAs (AUC = 0.68 and AUC = 0.78, respectively), while CD4 T cells were predictive of unruptured, stable IAs (AUC = 0.89). CONCLUSIONS: To our knowledge, we are the first to demonstrate a specific intracranial aneurysmal immune cascade that precedes rupture and delineate the ensuing changes that continue to develop afterwards. The findings underscore the complexity of IA immune pathophysiology, suggesting that immune cell behavior and gene expression patterns offer valuable insights into IA stability and potential rupture. This research paves the way for innovative, non-invasive strategies focusing on immunological markers for early IA management.