Different appearance and pathogenic roles of serum IgA against autologous IgG Fc and Fab in patients with IgA nephropathy.

The serum levels of IgA class antibodies against autologous IgG Fc and Fab fragments were measured by ELISA in 62 patients with primary IgA nephropathy (IgAN) and 20 normal healthy volunteers. Both antibodies were significantly higher in the patients (P less than 0.01). The total IgA levels were correlated with those of IgA anti-IgG Fc antibodies (IgA anti-Fc) (rs = 0.57, P less than 0.001), but not with those of the IgA anti-IgG Fab antibodies (IgA anti-Fab). A histopathological comparison revealed that the sera of patients with severe glomerulonephritis had significantly higher levels of IgA anti-Fc than those with milder lesions (P less than 0.01). On the other hand, no correlation was observed between the serum levels of IgA anti-Fab and the histopathological severity. A comparison before and after treatment in 12 patients demonstrated a significant decrease of IgA anti-Fc (P less than 0.01) and an increase of IgA anti-Fab (P less than 0.05) after the treatment. Size analysis in serial sera from 3 patients was performed using HPLC under neutral (pH = 7.0) and under acid (pH = 3.5) buffer conditions. A markedly increased ratio of both antibodies with the polymeric form was observed in the active phase. In the remission phase, the amounts of acid-dissociable polymeric form IgA anti-Fc were decreased. In contrast, high levels of polymeric form IgA anti-Fab continued to be observed in 2 patients at this phase. These results suggest that abnormally stimulated production of IgA class autoantibodies especially with the polymeric form against both IgG Fc and Fab fragments, occurs in IgAN, involving separate regulation with differing reactions to treatment and a distinct relationship between IgA anti-Fc and active histopathological lesions.