IgA-containing circulating immune complexes in patients with IgA nephropathy

Abstract

The role of circulating immune complexes in the pathogenesis of IgA nephropathy (Berger's disease) is controversial. Previous studies have shown that a minority of these patients have immune complexes, but the methods used have been able to detect only IgG- or IgM-containing circulating Immune complexes. Using a sensitive, specific Raji cell radioimmunoassay for IgA-containing circulating immune complexes, we have examined serum specimens from 12 patients with IgA nephropathy for the presence of IgA-containing circulating immune complexes. In addition, the Raji cell IgG assay and the 125I-C1q binding assay were used for the detection of IgG-or IgM-containing circulating immune complexes. Purified monoclonal antibodies against human IgA 1 and IgA 2 were used to determine the subclass of IgA present in renal biopsy specimens from five of these patients. Six of 12 (50 percent) patients had IgA-containing circulating immune complexes, whereas only two of 12 (17 percent) had positive results in the Raji IgG assay and one of 12 (8 percent) in the 125I-C1q binding assay. There was no correlation between serum IgA, C3, C4, or factor B levels and the presence or level of IgA-containing circulating immune complexes. None of the three patients with renal failure had circulating immune complexes of any type. Of the seven patients with disease duration of two years or less, five (71 percent) had IgA-containing circulating immune complexes, and three (43 percent) had IgG- or IgM-containing complexes. In all five renal biopsy specimens examined for IgA subclass, diffuse, heavy, mesangial deposits of IgA 1 were seen, whereas IgA 2 staining was absent or present in only trace amounts. These findings suggest that IgA 1 is the predominant antibody in renal biopsy specimens from patients with IgA nephropathy. The finding of IgA-containing circulating immune complexes in these patients—and their more frequent occurrence in patients with early stages of the disease—suggests that IgA-containing circulating immune complexes may play a role in the pathogenesis of IgA nephropathy.