Single-Cell RNA-Sequencing of Peripheral Blood Reveals Neutrophil Heterogeneity in Childhood ANCA-Associated Vasculitis.

Background: The intolerance of the body to neutrophil antigens drives the pathogenesis of childhood anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV), making neutrophils a central focus of research on the disease's underlying mechanisms. Methods: We performed single-cell RNA sequencing on 18 peripheral blood samples (including three healthy human samples, twelve samples from patients with different types of AAV, and three samples from patients after AAV treatment) to investigate neutrophil heterogeneity in AAV. These bioinformatics findings were subsequently validated through comprehensive experimental approaches, including in vitro cellular assays, in vivo animal studies, clinical sample analyses, and correlation with patient clinical data. Results: In AAV, neutrophils were reclassified into seven distinct clusters, Neutrophils2 (N2, CD10 Conclusion: These findings identify two novel pathogenic neutrophil subsets and suggest that modulation of glutamine metabolism is a promising avenue for further investigation as a potential therapeutic strategy in childhood AAV.