IgA, Glomerulonephritis and Liver Disease

Abstract

Data from our Unit suggest that soluble immune complexes (IC) are responsible for the mesangial deposits of IgA and C3 in patients with IgA nephropathy. These IC are of intermediate size (9-17S) and contain IgA, IgG and less commonly IgM. Ubiquitous exogenous antigens have been implicated in some patients and primary defects in antigen exclusion or reticuloendothelial sequestration have been proposed to account for the formation and persistence of IC. The liver plays a central role in the clearance of antigens, polymeric IgA and IC, and liver disease is associated with alimentary hyperimmunization, hypergammaglobulinaemia (including IgA polymers) and circulating IC. At autopsy, mesangial (14/28), skin (10/18) and choroid plexus. (2/3) deposits of IgA were found in patients with alcoholic cirrhosis compared with 1/15, 3/10 and 2/5 respectively in controls. Raised serum antibodies to E. coli and to BSA were noted in patients with alcoholic cirrhosis but no specific antibodies have been detected in the kidney eluates. Circulating IC and mesangial deposits of IgA and C3 have also been demonstrated in rats with carbon tetrachloride-induced cirrhosis and after portacaval shunting. Measurement of reticuloendothelial function and the clearance of IgA polymers and IC is now required in patients with primary IgA nephropathy and HSP. In the meantime, IgA nephropathy is best regarded as a syndrome with primary and secondary forms, and as a clinical spectrum from isolated glomerulonephritis to systemic IC disease (HSP).