Introduction Dynamic flow models have been useful in describing the development of intracranial aneurysms. However, our understanding of the mechanisms behind their remodeling and rupture is limited. Given that only a subset of patients who harbor this pathology go on to rupture, this question becomes especially relevant. There have been some studies, namely in reference to the natural history of thoracic and aortic aneurysms, that have described a role that regulatory B cells may play in rupture. However, they are limited in scope and application.
Hypothesis We hypothesized that there is an underlying immune driver that mediates the remodeling and rupture of intracranial aneurysms. Our goal was to describe the relevant immune populations and the phenotypic changes that occur between ruptured and unruptured pathologies. Ultimately, this study will inform the development of future immune-directed therapies for intracranial aneurysm management.
Methods We utilized endovascular techniques previously described to collect the endothelial lining of aneurysms in both ruptured and unruptured settings in our patient population. These cells were processed, sorted, and stained using the MaxPar Immune Profiling Panel surface markers (Standard Biotools, CA, USA) and data acquired using a time-of-Flight mass spectrometry (CyTOF Helios, Standard Biotools, CA, USA). We then developed Python clustering tools in conjunction with FlowJo Analysis Software (BD Biosciences, OR, USA) to perform unsupervised clustering visualization and analysis of high-parameter data.
Results We found a unique infiltrating population of regulatory B cells in ruptured aneurysms. This population is more prominent in high-grade ruptures and large, dysplastic aneurysms in the ruptured population. Further, we noted that while there are infiltrating immune populations in both ruptured and unruptured aneurysms, the myeloid/macrophage population in the ruptured aneurysms express a more inflammatory phenotype (associated with M2-type). Within the ruptured population, we compared patients with prior documented sentinel hemorrhages and re-ruptured aneurysms against new aneurysm ruptures. In the former population, we noted that there is an infiltrating memory T cell population that is not present in naïve ruptures.
Conclusion These findings all point to a complex, coordinated immune response that is driving both the remodeling of vessel wall and, ultimately, intracranial aneurysm rupture. This suggests that with further studies, we may be able to anticipate and prevent aneurysm rupture via adjunctive immune therapies.
Disclosures J. Antonios: None. T. Barak: None. B. Gultekin: None. K. Yalcin: None. A. Chamberlain: None. R. Hebert: None. C. Matouk: None. M. Gunel: None.
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