Immune Landscape Variation in Antineutrophil Cytoplasmic Antibody‐Associated Vasculitis Circulation Before and After Plasmapheresis by Single‐Cell Transcriptome

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases characterized by inflammation and destruction of small blood vessels. AAV could be fatal if left untreated. Prompt diagnosis and treatment are crucial to protect AAV-related organs and tissue. Plasmapheresis, a therapeutic intervention aimed at removing harmful substances from the blood, devotes benefits to AAV treatment. However, the specific immune mechanism underlying its effectiveness remains unclear. In our research, we used single-cell RNA sequencing (scRNA-seq) to study the variation of peripheral blood mononuclear cells (PBMCs) before and after plasmapheresis in AAV patients. From this work, we explored a novel method for monocyte classification. In addition, flow cytometry was used to detect the relationship between the monocyte clusters and AAV activity under the new monocyte clustering method. Our scRNA-seq results revealed significant changes in monocyte clusters following treatment, which could be classified into three clusters (CD14+ monocytes, FCGR1A+ monocytes, and FCGR3A+ monocytes). In addition, our flow cytometry results showed that FCGR3A+ (CD16+) monocytes were positively correlated with AAV activity, whereas FCGR1A+ (CD16-CD64+) monocytes were negatively correlated with AAV activity. This may be related to the different biological effects of CD16 and CD64 on monocytes after interacting with the Fc region of ANCAs. In conclusion, our research sheds light on the immune landscape of AAV before and after plasmapheresis, identifying specific monocyte clusters linked to disease activity. These findings offer insights for novel monitoring methods and therapeutic targets in AAV.