Circulating and mesangial secretory component-binding IgA-1 in primary IgA nephropathy

Abstract

In a prospective study of 38 patients who presented with hematuria of renal origin, 15 patients were found to have primary IgA nephropathy and 23 had other renal disorders. Sera and renal biopsy specimens of these patients were studied for the presence of macromolecular IgA1 and IgA2 using monoclonal antibodies, and the presence of J-chain as demonstrated either by immunofluorescence or its capacity to bind free secretory component. Circulating macromolecular IgA was found exclusively in the sera of patients (80%) with primary IgA nephropathy. In these sera the polymer/monomer ratio for IgA1 (0.64 +/- 0.13) was significantly higher than for normal human serum (0.39 +/- 0.01) (P less than 0.001), while no differences were found for IgA2. The polymeric IgA1 was isolated from serum by gel chromatography and was shown to have the capacity to bind free secretory component. Direct two-color immunofluorescence studies revealed the presence of only IgA1 in the mesangial deposits and also its capacity to bind free secretory component. We conclude (1) that demonstration of circulating macromolecular IgA in patients with renal hematuria is of diagnostic value and (2) that antigenetic similarities between the circulating and the mesangial macromolecular IgA suggest that dimeric IgA1 is deposited in the mesangium of patients with primary IgA nephropathy.