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 the predominant deposition of IgA in glomerular mesangium/ Serum IgA is often elevated in patients with IgAN and it has been postulated that it is responsible for the mesangial lesions. However, the direct effect of circulating IgA which were isolated from patients with IgAN on the thymidine uptake, superoxide and fibronectin production and fibronectin mRNA expression of cultured rat mesangial cells, and we compared the findings to the effects of IgA isolated from patients with non- IgA mesangial proliferative glomerulonephrits (MsPGN) and normal controls. IgA was isolated with affinity chromatography using cyanogens bromide activated sepharose 4B coupled to sheep anti-human IgA antiserum. Results: Our results demonstrate that both sera and IgA from patients with IgAN dose-dependently increased mitogenesis of mesangial cells as measured by [3H]-labeled thymidine uptake. The thymidine uptake by sera and IgA isolated from patients with IgAN was significantly higher than those of sera and IgA isolated from patients with IgAN was significantly higher than those of sera and IgA isolated from patients with MsPGN and normal controls. Sera and IgA from patients with IgAN significantly enhanced superoxide and fibronectin production, and fibronectin mRNA expression of mesangial cells. The superoxide and fibronectin production was also significantly higher compared to those of MsPGN and normal controls. Conclusion: The study indicates that circulating IgA isolated from patients with IgAN are different form patients with MsPGN and normal controls, and may potentially induce oxidative injury and production of extracellular matrix of glomerular mesangial cells in IgAN.

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