[New immunopathogenic aspects of IgA nephropathy]

Abstract

IgA nephropathy (Berger's disease) has become recognized worldwide as one of the most common of the primary glomerulonephritis. The mesangial granular deposits suggested an immune complex disease. The available data evidence that the IgA circulating immune complexes in these patients are heterogeneous. Recent analysis, performed after dissociating the complexes, found both IgA1 and IgG. In fact, high serum levels of IgA rheumatoid factor and shared antibody idiotypes were found in a large proportion of those patients. A close relationship was noted between the presence of cross-reactive idiotypes on mesangial immunoglobulins and the existence of increase levels of serum idiotypes and many patients have increased rates of IgA synthesis either spontaneously or after stimulation of the peripheral blood mononuclear cells by various mitogens. A lot of abnormalities on B and T lymphocytes, related with the IgA immune regulation, have been described. Most of deposited IgA in the mesangium is polymeric and belongs to the IgA1 class. Patients with IgA nephropathy have very often antibodies against exogenous and endogenous antigens. Among the most frequently found are the antibodies against dietary, viral and bacterial antigens as well as against the Fc and Fab portions of immunoglobulins, nuclear and glomerular antigens. The mechanisms of mesangial damage in IgA nephropathy are not well known. Mesangial cells are capable of producing and releasing various lipidic and proteic mediators. The stimulation of mesangial cells, cultured in vitro by IgA or IgG immune complexes induced the release of PAF, PGE2 and superoxide anion. A better knowledge of the mechanism implicated in the abnormality of IgA immune regulation, as well as of the glomerular inflammation response could afford a new therapeutic approach to this nephropathy.