Circulating and deposited immune complexes in patients with glomerular disease: immunopathologic correlations.

The presence of circulating immune complexes (ICs), and alterations of serum immunoglobulins G, A, and M, properdin factor B, and C3 and C4 levels were correlated with glomerular immune deposits in 50 consecutive renal biopsy patients. Urine from 25 of these patients was also examined for ICs. Agarose gel zone electrophoresis (AGE) was used for IC screening. This method detects greater than or equal to 200 ng of IC per 1.5 microliter sample application (approximately equal to 130 micrograms/ml of serum immune complexes) and gives some indication of antigen or antibody excess in the ICs. Glomerular immune deposits were detected by immunofluorescence and electron microscopy in 72% (36/50) of these patients. Circulating and/or urinary IC were found in 69% (25/36) of patients with positive immunofluorescence and 78% (11/14) of patients with negative immunofluorescence. Five of 11 patients with circulating IC but no renal deposition presented with idiopathic crescentic glomerulonephritis (ICGN). These results indicate that IC that persist in the circulation and/or pass renal glomeruli with minimal deposition may result in tissue injury. Circulating IC in antibody excess were detected in all patients with membranous glomerulonephritis. ICs were also found in 55% of patients with IgA nephropathy. Our observations support the hypothesis of an immune complex pathogenesis for these diseases. Determination of circulating and urinary IC in patients with glomerular disease may help in clinical assessment and provide information concerning the pathogenesis of these diseases in humans.