Whether
IgA nephropathy is attributable to mesangial
IgA is unclear as there is no correlation between intensity of deposits and extent of glomerular injury and no clear mechanism explaining how these mesangial deposits induce
hematuria and subsequent
proteinuria. This hinders the development of a specific
therapy. Thus, precise events during deposition still remain clinical challenge to clarify. Since no study assessed induction of
IgA nephropathy by nephritogenic
IgA, we analyzed sequential events involving nephritogenic
IgA from
IgA nephropathy-prone mice by real-time imaging systems. Immunofluorescence and electron microscopy showed that serum
IgA from susceptible mice had strong affinity to mesangial, subepithelial, and subendothelial lesions, with effacement/actin aggregation in podocytes and arcade formation in endothelial cells. The deposits disappeared 24-h after single
IgA injection. The data were supported by a fluorescence molecular tomography system and real-time and 3D in vivo imaging. In vivo imaging showed that
IgA from the susceptible mice began depositing along the glomerular capillary from 1 min and accumulated until 2-h on the first stick in a focal and segmental manner. The findings indicate that glomerular
IgA depositions in IgAN may be expressed under the balance between deposition and clearance. Since nephritogenic
IgA showed mesangial as well as focal and segmental deposition along the capillary with acute cellular activation, all glomerular cellular elements are a plausible target for injury such as
hematuria.