Charge and Idiotypy of Pathogenic Antibodies in Sle

Hahn, Bevra

Abstract

These hypotheses will be tested - 1) that pathogenic antibodies in tissues and sera of patients with SLE can be identified by their charge, 2) that pathogenic antibodies can be identified by their idiotypes (Id), and 3) that these antibodies are not associated with tissue damage when the appropriate anti-idiotypic antibodies (anti-Ids) are present in serum. Sera from 200 patients with SLE will be studied for charge, Id, and anti-Id. When possible, serum will be obtained at the time of tissue biopsy (especially kidney and skin), and tissue will be studied for deposits of Id. Serial studies will be performed in serum specimens from 100 patients. Charge and Id will be studied on IgM monoclonal antibodies to DNA obtained from patients with SLE. Finally, clinical and serologic characteristics of each patient at the time serum and tissue are obtained will be analyzed for correlations with charge, Id, and anti-Id. Studies of antibody charge will be performed using isoelectric focusing (IEF) with autoradiography after overlay with antigens, Id, or anti-Id. Id/anti-Id will be assayed in IEF/autography and solid phase radioimmune or ELISA assays using murine monoclonal Ids and anti-Ids as probes. Several monoclonal anti-Ids have been developed - one which reacts with a public Id on mouse and human cationic IgG (DNA-binding and non-DNA-binding) from individuals with nephritis, and 7 which react with Ids on IgG from patients without nephritis. Additional anti-Ids will be made. These studies should define charge and Id characteristics associated with antibodies likely to cause nephritis,, dermatitis, or other manifestations of SLE if anti-Id is absent. They should therefore serve as useful diagnostic/prognostic reagents. Furthermore, they may define antibody subpopulations which would be targeted for specific immunosuppression with therapeutic anti-idiotypic reagents.