Study of pathogenesis of IgA nephropathy

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IgA nephropathy (IgAN) is characterized by the presence of IgA deposits, predominantly in the glomerular mesangium, and by mesangial proliferative glomerulonephritis (GN). Concerning its pathogenesis, several investigators have suggested that the deposited IgA is an antibody (Ab) to viral, bacterial or dietary antigens. Nevertheless, attempts to isolate a specific IgA circulating immune complex-associated antigen in patients with IgAN have been unsuccessful.We have shown that mucosal infection such as pharyngitis are often associated with the acute onset of IgAN. IgAN is, then, an immune complex disease that is caused by a poor mucosal immune response to environmental antigens to which the patient has been chronically exposed. We have observed previously that Haemophilus parainfluenzae (HP) is more commonly isolated from the pharynx of patients with IgAN than from those with other diseases. We have also identified the glomerular deposition of outer membranes of HP antigens (OMHP) and a … More n increased serum concentration of IgA-Ab against OMHP in patients with IgAN. Furthermore, We have shown that patients with IgAN have a specific increase in the production of IgA-Ab against OMHP via polyclonal activation against these, with switching of production from one isotype to another, e. g. from IgM to IgA.Our objective was to clarify the immune response between OMHP and lymphocytes in tonsils from patients with IgAN or controls. Patients with IgAN showed a significantly higher level of stimulation index to OMHP than controls. Lymphocytes from patients with IgA N also showed a significant higher level of IgA Ab and IgA1 against OMHP in culture supernatants than those from controls. Patients with IgA N showed positive correlations between IgA- and IgG-Ab, between IgA- and IgM-Ab, and between IgG and IgM-Ab against OMHP after OMHP stimulation.These results suggest that OMHP stimulate tonsillar T- and B-lymphocytes in patients with IgA N and that the immune response to OMHP may play a role in the pathogenesis of IgAN. Less