IgA glomerular deposits in experimental cirrhosis.

Lewis rats rendered cirrhotic by the administration of carbon tetrachloride developed mesangial and glomerular capillary wall deposits of immunoglobulins (especially IgA) and complement. These rats also had circulating immune complexes and markedly elevated serum IgA concentrations. The model suggests that defective hepatic sequestration of circulating IgA polymers and immune complexes may be responsible for the glomerular deposits. A similar mechanism may account for the high incidence of glomerulonephritis in patients with alcoholic cirrhosis.

Immunologic studies in IgA nephropathy.

Circulating immune complexes (CIC) were detected in 43.6% of 78 patients with primary IgA nephropathy by the solid-phase Clq radioimmunoassay. The IC were intermediate (9 to 17S) in size and contained IgA, IgG, and less commonly IgM. CIC were often present intermittently, correlating with episodes of macroscopic hematuria. Elevated serum IgA concentrations (38.7%) did not correlate with the detection of CIC. Similar findings were observed in sera samples from patients with Henoch Schonlein purpura and in IgA glomerulonephritis associated with alcoholic cirrhosis and/or portal systemic shunts. The factors responsible for the mesangial localization of the IC are not clear, but elevations in serum antibody titers to respiratory pathogens (mycoplasma pneumoniae, herpes virus, influenza), gut flora (E. coli 07), and bovine serum albumin suggest that common exogenous antigens may be involved in the pathogenesis. Primary defects in either mucosal antigen exclusion or reticuloendothelial IC sequestration are proposed to account for these findings.

Circulating immune complexes in IgA deficiency.

Circulating immune complexes (IC) were demonstrated in patients with serum IgA deficiency. Sixteen of thirty-one IgA deficient patients had serum IC detected by solid phase C1q radioimmunoassay for IgG class complexes. The presence of cryoglobulins (thirteen out of thirty-one patients) and increased polyethylene glycol precipitation (ten out of thirty patients) provided additional evidence for the presence of IC. Fourteen patients were asymptomatic but seven had clinical evidence of disease which could have been IC mediated: two with glomerulonephritis, three with polyarthritis, one with vasculitis and one with thyroiditis. Serum IC remained detectable in multiple samples over several months but this correlated poorly with the presence or absence of disease. Serum antibody to IgA was detected in fifteen out of thirty-one patients. There was no direct relationship between the presence of IC and the level of serum anti-IgA antibody; however, this antibody was shown to be present in the IC isolate in eight patients. It is proposed that a considerable portion of the IC load in IgA deficiency results from defective antigen exclusion at the level of the mucosa.

In vitro degradation of mouse, rabbit and dog antibodies to Vibrio cholerae by succus entericus.

Purified antibodies to Vibrio cholerae from mouse, rabbit and dog were digested in vitro by homologous intestinal secretions. When assessed with regard to their complement-dependent vibriocidal activity, IgG antibodies were generally more susceptible to degradation than IgM antibodies, High levels of tryptic inhibitors were required to inhibit this digestion. Rabbit IgG was unusual in being quite resistant to digestion. Gel filtration studies demonstrated that secretory IgA, isolated from mouse intestinal secretions, was resistant to proteolysis. Similar studies on dog IgG and mouse IgM demonstrated production of F(ab') 2-like fragments. Digestss of these antibodies, while devoid of Fc-mediated vibriocidal activity, retained significant protective activity for baby mice.