Immune cells have been detected in intracranial aneurysms (IAs). However, the causal effect of immune cell phenotypes on IAs remains unclear and difficult to comprehensively analyze.

Instrumental variables for 731 immunophenotypes were extracted from publicly available genetic databases. The influence of these immune cell traits on IAs was evaluated using the Mendelian randomization (MR) method. Five MR analysis methods, with inverse-variance-weighted as the main method, along with a comprehensive sensitivity analysis, were used to determine reliability of the results. Multivariable MR analysis was performed to correct for interactions between different immune cell phenotypes.

Overall, 27 immune cell traits exhibited significant causal effects on IAs. Among them, 13 immunophenotypes increased the risk of IA progression. Conversely, 14 immune cell characteristics might protect against IAs. Following false discovery rate correction, two hazardous and three protective immunophenotypes remained significant. Moreover, multivariate MR analysis showed that only naive CD4− CD8− T cells %T cells remained causally associated with a risk of IA, while CD19 on IgD+ CD38− naive B cells inhibited development of IAs.

Our study shows that immune cell traits and IAs are causally correlated, providing a new theoretical framework for understanding immune-IA crosstalk.