Innate Immune Cell Profiling in Peripheral Blood Mononuclear Cells of Patients with Moyamoya Disease.

Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by stenosis or occlusion of the internal carotid artery, thus leading to ischaemic and haemorrhagic strokes. Although genetic studies have identified ring finger protein 213 (RNF213) as a susceptibility gene, the low disease penetrance suggests that a secondary trigger, such as infection, may initiate disease onset. This study aimed to characterize the innate immune cell profile of peripheral blood mononuclear cells (PBMCs) of MMD patients via mass cytometry (CyTOF). Blood samples from 10 MMD patients and 10 healthy controls were analysed, with a focus on natural killer (NK) cells, monocytes, and dendritic cells (DCs). The results revealed significant changes in the NK and monocyte subpopulations in MMD patients; specifically, there was a decrease in the CD56CD16 NK03 subset and an increase in CD163 classical monocytes, thus indicating compromised microbial defences and heightened inflammation. Additionally, significant changes were observed in DC subpopulations, including an increase in CCR7 mature DCs and a decrease in CD141 and CD1c DCs. Overactivation of the TLR/MyD88/NF-κB pathway was observed in most innate immune cells, thus indicating its potential role in disease progression. These findings provide novel insights into immune dysfunction in MMD and highlight potential therapeutic targets.