Investigations of the pathogenesis and treatment of lupus nephritis are facilitated by the availability of inbred strains of mice that develop disease similar to human systemic lupus erythematosus. The natural evolution of the diverse histologic features of murine lupus nephritis is being studied to delineate the types of glomerular and tubulo-interstitial lesions as well as the characteristics of the immune deposits. Monoclonal antibodies and immunoperoxidase staining of frozen sections are employed to study the types and distribution of lymphoid cells in glomerular, vascular and tubulo-interstitial lesions. Changes in mesangial clearance of a macromolecular tracer, ferritin, will be related to these features of progressive glomerular disease. Ferritin is injected intravenously at various stages of the disease and the deposition of the exogenous protein is studied by light, immunoperoxidase and electron microscopic techniques. The impact of biologic response modifiers (eg. tumor necrosis factor and/or lipid A) on serologic and renal histologic features is being investigated. The goal is to develop a model of a flare of lupus nephritis which would facilitate further investigations of immunopathogenetic mechanisms. Innovative treatment strategies will be studied to refine our approach to this disease. Clinical, histologic and immunologic outcome parameters will be evaluated including detailed studies of renal morphology, and flow cytometry analysis of the characteristics of peripheral blood lymphocytes and splenocytes.
