Integrated single-cell chromatin and transcriptomic analyses of peripheral immune cells in patients with alopecia areata.

Introduction: Alopecia areata (AA) is an autoimmune disorder characterized by non-scarring hair loss ranging from mild, self-limiting episodes to severe and chronic forms. While prior research has primarily focused on lesional skin, the contribution of systemic immune cells remains underexplored. Methods: We performed integrated single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) on peripheral blood mononuclear cells (PBMCs) from patients with mild and severe AA, as well as healthy controls. A total of 32,453 high-quality cells were analyzed across 36 immune cell subtypes. Results: In AA patients, especially those with severe disease, we observed increased transcriptional heterogeneity, cytokine and chemokine pathway activation, and upregulation of antigen-presentation machinery enriched in TH1, TH2, and TH17 signatures. Chromatin accessibility profiling revealed 42,248 significant peaks with pronounced epigenetic remodeling in Discussion: Our results provide the first integrated single-cell chromatin and transcriptomic map of peripheral immune dysregulation in AA. These findings uncover systemic alterations associated with disease severity and identify candidate pathways for immune modulation and therapeutic targeting.