Integrated bulk RNA sequencing and mass cytometry analysis reveal the circulating immune landscape in ischemic and hemorrhagic Moyamoya disease.

Background: Moyamoya disease (MMD) is increasingly recognized as being influenced by chronic inflammation, with circulating immune cells playing a role in its progression. However, research on the immune characteristics of different MMD subtypes is limited. This study aims to compare the peripheral immune profiles of ischemic and hemorrhagic MMD patients.

Methods: Peripheral immune profiles were analyzed using transcriptome sequencing and mass cytometry. Data preprocessing was followed by functional and gene set enrichment analyses, as well as the construction of immune-related gene sets and protein-protein interaction networks. High-dimensional data analysis was performed using the PhenoGraph and t-SNE algorithms.

Results: The study involved 9 ischemic and 6 hemorrhagic MMD patients for transcriptome analysis, and 20 ischemic and 16 hemorrhagic patients for mass cytometry. Hemorrhagic MMD patients exhibited upregulated genes associated with inflammation, hypoxia, and bacterial responses and downregulated genes related to immune response regulation. The results of mass cytometry analysis showed that, compared to ischemic MMD, patients with hemorrhagic MMD had reduced CD3 expression levels in T cells and their specific subsets, as well as impaired chemotactic capacity of DPT cells. The function of the B03 subset in B cells was diminished, while the proportion of NK cells increased and that of monocytes decreased. Additionally, the proportions of the D03 and D07 subsets in dendritic cells (DCs) were elevated.

Conclusions: This study reveals distinct immune profiles in ischemic and hemorrhagic MMD, emphasizing the need for subtype-specific therapeutic strategies.