Differential effects of circulating IgA isolated from patients with IgA nephropathy on superoxide and fibronectin production of mesangial cells

Background: IgA nephropathy (IgAN) is characterized by predominant depositi on of IgA in the glomerular mesangium. Serum IgA is often elevated in patie nts with IgAN, and it has been postulated that it is responsible for the me sangial lesions. However, the direct effect of circulating IgA on mesangial cells is not clear, Methods:We investigated the effects of sera and IgA wh ich were isolated from patients with IgAN on thymidine uptake, superoxide a nd fibronectin production and fibronectin mRNA expression of cultured rat m esangial cells, and we compared the findings to the effects of IgA isolated from patients with non-IgA mesangial proliferative glomerulonephritis (MsP GN) and normal controls. IgA was isolated with affinity chromatography usin g cyanogen bromide activated Sepharose 4B coupled to sheep antihuman IgA an tiserum. Results: Our results demonstrated that both sera and IgA from pati ents with IgAN dose-dependently increased mitogenesis of mesangial cells as measured by H-3-labeled thymidine uptake. The thymidine uptake by sera and IgA isolated from patients with IgAN was significantly higher than that of sera and IgA isolated from patients with MsPGN and normal controls. Sera a nd IgA from patients with IgAN significantly enhanced superoxide and fibron ectin production and fibronectin mRNA expression of mesangial cells. The su peroxide and fibronectin production was also significantly higher as compar ed with patients with MsPGN and normal controls. Conclusions: Our results i ndicate that circulating IgA isolated from patients with IgAN is different from that of patients with MsPGN and normal controls and may potentially in duce oxidative injury and production of extracellular matrix of glomerular mesangial cells in IgAN. Copyright (C) 2001 S. Karger AG, Basel.