Nephritogenic immune reactions involving immune complex formation in the circulation and in situ within the kidney

The circulating immune complex (IC) mechanism of renal and vascular injury is now well established based on observations in experimental serum sickness in animals and detection of circulating and localized IC of known antigen and antibody content in glomerulonephritis (GN) in man. Studies continue on the factors responsible for formation and vascular deposition of circulating IC. Utilization of assays to detect circulating IC has revealed that some patients with chronic presumed IC GN have no unusual amount of circulating IC. The possibility that nephritic individuals may handle relatively normal amounts of circulating IC in a nephritogenic fashion points out the need to study host and genetic factors in the development of IC GN. Observations in experimental animals have demonstrated the nephritogenic potential of the direct reaction of antibody with antigens, either structural in nature or "planted" within the glomerulus in a discontinuous pattern. This suggests that some GN previously thought to be from deposition of circulating IC IC by the pattern of irregular Ig accumulation on immunofluorescence study might be the product of a direct reaction of antibody with glomerular capillary wall antigens. Models of such reactions involving nonclassic glomerular basement membrane (GBM) glomerular capillary wall antigens are being identified in animals and sought in man. Finally, the reaction of antibodies with foreign materials that are first trapped or "planted" within the glomerulus can be nephritogenic in animal models and conceivably in man. The local nephritogenic immune reaction within the glomerulus should not distract from the circulating IC mechanism but rather expand our ideas of how the immune system can damage the kidney.