The work will characterize pathogenic mechanisms of disease in patients with systemic lupus erythematosus (SLE). New knowledge will be sought on how immune complexes will deposit in tissues, using experimental animals. Previous studies have shown that patients with SLE have IgG in circulation that binds to Ckq in solid phase assays. Immunochemical techniques techniques will be used to determine if these molecules bind to Clq as antibodies or as small immune complexes. The isoelectric points of antibodies in large immune complexes of patients with SLE will be determined by isoelectric focusing and these findings will be related to the nature of renal disease of these patients. These studies will determine if charge-charge interactions contribute to glomerular deposition of immune complexes in patients with SLE. The nature and specificity of antibodies and antigens will be determined in serum immune complexes of patients with SLE. After evaluation of elution and detection methods with material from mouse models, the nature of antibodies and their specificity in immune material from mouse models, the nature of antibodies and their specificity in immune deposits at the dermal-epidermal junction of patients with SLE will be determined. In experimental animals mechanisms of immune complex deposition in glomeruli will be studied. The deposition in glomeruli of immune complexes with complement components will be tested. The contribution of positively charged regions of antigen molecules to deposition in glomeruli by charge-charge interaction will be investigated. The contribution of hypertension to mesangial deposition of immune complexes will be evaluated. The role of concentration dependent polymerization of macromolecules in deposition in glomerular mesangium will be examined with native and modified macromolecules for which polymerization will be characterized.
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