Identification of transcription factors related with renal injury in IgA vasculitis

IgA vasculitis (IgAV) is the most common systemic vasculitis in children. The progression of IgA vasculitis nephritis (IgAVN) to chronic kidney disease can be as high as 20%. However, the molecular mechanism underlying IgAVN pathogenesis remains unclear. We extracted total RNA from peripheral blood mononuclear cells (PBMCs) of 15 children with IgAV and 15 children with IgAVN and performed RNA sequencing. We examined lymphocyte subsets in 118 children with IgAVN and analyzed the percentages of CD4 + , CD8 + , B, and NK cells in peripheral blood samples from the Mycoplasma pneumoniae (MP)-IgAVN and NO MP-IgAVN. The expression of T cell markers and their cytotoxic activity in peripheral blood from MP-IgAVN and NO MP-IgAVN patients were measured by flow cytometry. Cytoscape software identified three transcription factors (TFs) regulating differentially expressed target genes between IgAV and IgAVN, namely CEBPB, NFY, and HSF2. The mRNA expression of these TFs in IgAVN was significantly increased. The expression levels of each of these three TFs were positively correlated with microalbumin and 24-hour urinary protein levels. The MP infection rate in IgAVN patients is significantly higher than that in IgAV patients. The percentages of CD8 + T cells, CD44 + CD62L + T cells, and granzyme B (GZMB) expression in MP-IgAVN were significantly higher than those in NO MP-IgAVN. The titer of MP antibodies was positively correlated with HSF2 mRNA expression in IgAVN. Furthermore, the pathological stage of renal tissue in MP-IgAVN was more advanced than that in NO MP-IgAVN. Our study indicates that the transcription factors CEBPB, NFY, and HSF2 may be closely associated with the degree of renal injury in IgAVN and may serve as potential molecular markers for assessing renal damage in IgAVN. MP infection may contribute to the development of IgAVN through the modulation of HSF2 expression. This regulation promotes the inflammatory response and enhances the cytotoxic function of T cells.