{
  "abstract": "Objective Intracranial aneurysm (IA) formation and rupture are increasingly recognized as inflammatory processes, yet the immune landscape governing aneurysm stability remains poorly defined. We sought to characterize IA immune architecture using endoluminal biopsy coupled with single-cell proteomic and transcriptomic profiling.Methods We performed a prospective observational study of patients undergoing endovascular treatment for intracranial aneurysms. Endoluminal biopsy samples were obtained using coils and microcatheter tips, followed by single-cell immune profiling with mass cytometry (CyTOF) and single-cell RNA sequencing (scRNA-seq). Immune cell populations and gene expression profiles were analyzed in relation to aneurysm stability (ruptured, unruptured growing, and unruptured stable) and clinical variables.Results Fifteen high-quality IA samples underwent CyTOF analysis, revealing a diverse immune microenvironment comprising 11 major immune cell populations. Unsupervised clustering identified two distinct immune phenotypes that strongly correlated with aneurysm stability (p=0.0097), independent of traditional clinical risk factors. Unstable aneurysms (ruptured and growing) demonstrated a shift toward innate immune predominance, with significant enrichment of neutrophils, whereas stable aneurysms exhibited a more balanced immune composition. Neutrophils in ruptured IAs displayed an activated phenotype characterized by increased expression of CD38, HLA-DR, and CCR7, suggesting enhanced chemotaxis and antigen-presenting capacity. Complementary scRNA-seq analysis identified distinct transcriptional programs across aneurysm states, with ruptured aneurysms enriched for genes associated with acute inflammation and tissue remodeling, while growing aneurysms demonstrated upregulation of immune activation and trafficking pathways. Stable aneurysms exhibited gene signatures consistent with immune regulation and suppression.Conclusions Endoluminal biopsy combined with single-cell multiomic profiling reveals distinct immune signatures associated with intracranial aneurysm stability. Aneurysm progression is characterized by a shift from adaptive immune balance toward innate immune activation, particularly neutrophil-driven inflammation. These findings provide a foundation for the development of immune-based biomarkers and targeted therapies aimed at preventing aneurysm growth and rupture.Disclosures J. Antonios: None. B. Theriault: None. N. Sujijantarat: None. R. Hebert: None. T. Barak: None. M. Gunel: None.",
  "authors": [
    {
      "affiliations": [
        "Neurosurgery, Yale, New Haven, CT"
      ],
      "name": "J Antonios"
    },
    {
      "affiliations": [
        "Yale University, New Haven, CT"
      ],
      "name": "B Gultekin"
    },
    {
      "affiliations": [
        "Neurosurgery, Yale, New Haven, CT"
      ],
      "name": "B Theriault"
    },
    {
      "affiliations": [
        "Neurosurgery, Yale, New Haven, CT"
      ],
      "name": "N Sujijantarat"
    },
    {
      "affiliations": [
        "Neurosurgery, Yale, New Haven, CT"
      ],
      "name": "R Hebert"
    },
    {
      "affiliations": [
        "Yale University, New Haven, CT"
      ],
      "name": "C Matouk"
    },
    {
      "affiliations": [
        "Neurosurgery, Yale, New Haven, CT"
      ],
      "name": "T Barak"
    },
    {
      "affiliations": [
        "Neurosurgery, Yale, New Haven, CT"
      ],
      "name": "M Gunel"
    }
  ],
  "title": "O-063 Immune signatures of intracranial aneurysm stability revealed by endoluminal biopsy and single-cell multiomics",
  "uid": "7c971957-201d-5822-a126-e48057206bc5"
}