Peripheral Immune and Metabolic Dysregulation in Migraine, Ménière's Disease, and Vestibular Migraine: A Single-Cell Atlas Study.

Abstract

Background Migraine (MI), Ménière's disease (MD), and vestibular migraine (VM) share significant clinical and pathological similarities, particularly their link to neurological dysfunction and immune cell activity, though mechanisms remain poorly understood. Methods We utilized a single-cell RNA sequencing dataset of peripheral blood mononuclear cells from eight patients with MD, five patients with MI, five patients with VM, and six healthy controls. A cross-disease cell atlas was constructed via cellular heterogeneity and dynamic cell abundance analysis. Further studies analyzed metabolic heterogeneity and performed differential expression analysis across all groups. The core regulatory pathways were identified using gene set enrichment and pathway analyses. Additionally, herbal and compound screenings related to targets in MI were performed. Pseudotime analysis was then employed to infer the evolutionary trajectories, identifying key genes associated with differentiation. Results We identified 42,198 cells grouped into 16 clusters and classified into five cell types: T cells, B cells, dendritic cells, natural killer cells, and monocytes. Among these, T cell abundance significantly increased, whereas monocytes were essential for metabolic reprogramming. Notably, the upregulated MAPK signaling pathway was identified as the core regulatory pathway. A total of 1571 interaction pairs were screened between matched targets for herbs and compounds. T cell trajectory analysis revealed two differentiation pathways originating from CD8 + T cells that diverged into CD4 + T cells and naïve T cells. PRKCA was significantly upregulated during differentiation, being highly expressed in the disease groups. Conclusions This study identified distinct immune cell patterns in MI, MD, and VM, with notable T cell imbalances. PRKCA was highlighted as a core regulator of disease mechanisms via the MAPK pathway, laying the groundwork for future research into therapies and disease understanding.