Composition of IgA-containing circulating immune complexes in IgA nephropathy.

Macromolecular IgA is found with a relatively high frequency in the sera of patients with IgA nephropathy (IgAN). This macromolecular IgA consists of polymeric IgA, IgA-containing immune complexes, or both. The presence of polymeric IgA antibodies reflects a recent IgA response. Vaccination data in patients with IgAN suggest that these patients respond more vigorously with their mucosal immune system than do controls. The association of exacerbations with upper respiratory tract infections suggests that the immunogenic stimuli probably are of microbial origin and are presented to mucosal surfaces. Analysis by sucrose density ultracentrifugation has shown that the macromolecular IgA may contain IgG, IgA rheumatoid factor, and C3. The search for the antigen or antigens specifically responsible for IgAN has been unsuccessful. Although IgG and IgA rheumatoid factor may contribute, they do not account for the pathogenesis of the disease in all patients. Alternative mechanisms have to be assumed for patients who do not have detectable levels of IgA-containing immune complexes. They could have polymeric IgA or IgA-containing immune complexes intermittently, as has been shown in children with relapsing IgAN. The binding of circulating IgA antibodies to antigens present in the mesangium can lead to the local formation of deposits in the absence of circulating IgA complexes.