Comprehensive Profiling of Peripheral Blood Mononuclear Cells Reveals Monocyte-CD8+ T cell-B cell Communication as Central Cell-cell Interaction and pathogenesis in IgA Vasculitis

IgA vasculitis (IgAV) is a common vasculitis which often occurs in children. IgAV is characterized by the vasculitis caused by IgA deposition in the walls of small vessels. The mechanisms of immune disorders in IgAV, as well as the innmue network regulation between immune cells is still unclear. Dissecting the IgA-secreting B cells is crucial for understanding the pathegenesis mechanisms of IgA deposition in IgA vasculitis (IgAV). Here, we used single-cell RNA sequencing to profile immune cells in peripheral blood mononuclear cells of IgAV. MIF induced IgA secretion in IgAV, and monocyte-CD8+ T cell-B cell communication regulated MIF pathway. ICAMs pathway regulated monocyte-CD8+ T cell-B cell communication, and promoted B cells adhension in IgAV. CD8+ T cell was the key cell in monocyte-CD8+ T cell-B cell communication. TCR repertoire analysis identified a specific CD8+ Temra cluster with specific TCR clonetypes. BCR repertoire analysis revealed the existence of IgA Fc-specific IgG in serum of IgAV nephritis. These findings reveals complicated immune regulation in IgAV, emphrazing the importance of MIF and ICAMs pathways in cell-cell interaction, discovering CD8+ T cells' crucial function for IgAV pathogenesis, and bringing new insights into the pathegenesis of IgA deposition in IgAV. Overall design: Both IgAV patients and controls were collected from Wuhan Children's Hospital.