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. Thus, the Ab is probably produced as part of the specific host immune response to various environmental antigens. Such reports strengthen the possibility of a relationship between mucosal immunity and the pathogenesis of IgAN.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 byb a poor mucosal immune response to environmental antigens to which the patient has been chronically exposed. We have observed previously that Haem … More ophilus 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 an 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 productiion 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,and that a significant relationship between IgA-Ab against OMHP and renal lesions exists in patients with IgAN.Our objective was to clarify the immune response between OMHP and lymphocytes in tonsils from patients with IgAN or other glomerular diseases (OGDs) by measuring thymidine uptake. Patients with IgAN showed a significantly higher level of stimulation index (^3H-thymidine uptake by the stimulated lymphocytes by OMHP (cpm)/^3H-thymidine uptake by the unstimulated lymphocytes (cpm) than did patients with OGDs.These results suggest that the immune response between OMHP and lymphocytes in tonsils play a role in pathogenesis of IgAN. Less