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 tubulointerstitial lesions. Monoclonal antibodies and immunoperoxidase staining of frozen sections are employed to study the types and distribution of immunoglobulin deposited and the characteristics of the lymphoid cells in glomerular, vascular and tubulointerstitial lesions. The impact of biologic response modifiers on immunologic features is being investigated. The goal is to develop a model of a flare of lupus nephritis which would facilitate further investigations of immunopathogenic 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, the characteristics of peripheral blood lymphocytes and splenocytes employing flow cytometry, measures of immunoglobulin gene expression, and in vitro assays of alterations in humoral and cell mediated immune regulation.
