Abstract
The aim of our study is to elucidate the relationship between IgA subclasses and complement activation in IgA glomerulonephritis (IgAGN). Immunohistological staining was performed on biopsied renal specimens obtained from 26 patients with IgAGN who received repeated biopsy, using antibodies against IgG, IgA, IgA1, IgA2, IgM, C1q, C3c, C4, factor B, mannose-binding lectin (MBL) and MBL-associated serine protease-1 (MASP-1). Mesangial deposits of both IgA1 and IgA2 were found in 11 of 26 patients at the first biopsy, accompanied by mesangial deposits of C3c, C4, factor B and MBL/MASP-1. Mesangial deposits of IgA2 and MBL/MASP-1 were colocalized. The remaining 15 patients showed mesangial deposits of IgA1 alone with neither C4 nor MBL/MASP-1, accompanied by mesangial deposits of C3c in 13 and factor B in 15. Mesangial deposits of Iga1, Iga2 and MBL/MSAP-1 were found in 15 patients at the second biopsy, including 4 with mesangial deposits of IgA1 alone at the first biopsy. The remaining 11 patients showed mesangial deposits of IgA1 alone with neither C4 nor MBL/MASP-1 at the second biopsy. Proteinuria was unchanged in patients with mesangial deposits of both IgA1 and IgA2 in spite of treatment, whereas proteinuria remarkably decreased in those with mesangial deposits of IgA1 alone at the second biopsy. There was no difference in the clinical outcome and the histological severity between those with and without mesangial deposits of IgA2. We reconfirmed immunohistologically that mesangial deposits of IgA1 might activate the alternative pathway, and mesangial deposits of IgA2 might activate the lectin pathway. Our current study indicates a novel evidence that IgA2 subsequently deposits in the mesangial area where IgA1 already deposited, and proteinuria prolongs in those with mesangial deposits of both IgA1 and IgA2.
