- In patients with SLE kidney involvement is the most frequent serious manifestation of the disease. The renal lesions are caused by immune complexes in glomeruli. The composition of these immune complexes has not been fully established. DNA and antibodies to DNA have been thought to be the major components of these deposits. Recent evidence indicates that other antigen-antibody systems may contribute significantly to the renal disease of SLE. In particular, the autoantibodies to the collagen-like region of C1q, a component of the complement system, are involved as shown by recent results. The proposed work will extract and characterize the antibody molecules present in glomeruli of patients with SLE. Kidney specimens will be obtained at autopsy from patients with lupus. Glomeruli will be isolated and glomerular basement membrane fragments will be prepared. Antibodies will be extracted from these fragments and quantified. Sensitive immunochemical methods will be used to identify the presence of specific antibodies. This will include antibodies specific to double-stranded DNA, single-stranded DNA, C1q, Sm antigens, SS-A, SS-B, and chromatin. These antibodies have been extensively investigated in the serums of patients with SLE, but their presence in the immune deposits in glomeruli of these patients has not been examined in sufficient detail. The ability of autoantibodies to the collagen-like region of C1q to generate inflammation will be examined in vitro, using cytokine and chemokine release from monocytes. Methods will be developed and evaluated to detect specific antibodies on renal biopsy specimens. The completion of these investigations will provide new knowledge needed for future studies directed at controlling the antibody response to specific antigens that contribute to the renal disease of SLE.
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