The proposed research on the renal disease of systemic lupus erythematosus seeks to clarify pathogenic mechanisms in patients and to develop new knowledge on deposition of immune complexes in experimental animals. Since evidence from experimental animals has shown that only large-latticed immune complexes deposit in the subendothelial and mesangial areas of glomeruli, the size distribution of circulating immune complexes will be determined at the time of diagnostic renal biopsy. These findings will be related to the ultrastructural localization of glomerular deposits. Since in experimental animals the hepatic mononuclear phagocyte system is the major organ for removing circulating immune complexes, abnormalities in this function will be tested in patients by using a recently developed probe. This probe consists of stable, reproducible aggregates of human IgG. An abnormality in handling of circulating complexes may be an important pathogenic factore in systemic lupus. In experimental animals studies will be conducted to gain new information on the mechanisms of immune complex deposition in glomeruli. The role of the fixed negative charge in glomeruli will be evaluated by modifying the charge on deposited complexes, by selecting positively and negatively charged antibodies, and by recovering the deposited complexes. The role of antibody avidity in the localization of immune complexes will be determined and the importance of rearrangement of immune complex lattice in immune deposits will be studied, both with the aid of covalently cross-linked immune complexes. The possible contribution of renal lymph flow to deposition of immune complexes will be examined. The fate and localization of immune complexes with the third component of complement will be studied. These studies should yield significant new knowledge that can then be applied to human lupus glomerulonephritis.
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