The objectives are to continue to investigate immunopathogenic mechanisms in pemphigus and bullous pemphigoid. We have recently presented evidence that complement is fixed to epidermal cell surfaces by pemphigus antibody, that complement enhances pemphigus IgG mediated detachment of epidermal cells, and that complement in the presence of pemphigus IgG alters the integrity of epidermal cell membranes.
Under Aim I, we hope to study further this complement mediated attack upon the epidermal cell by immunofluorescent (IF), immunoelectron microscopy (IEM), and by cell detachment assays. We hope to determine which component(s) is involved in the process and if complement activation enhances the release of plasminogen activator. As pemphigoid antibody reacts with the polar region of basal cells, we would also like to propose to determine if complement will damage basal cell membranes as well (Aim II). Our last aim is to continue to purify the antigens involved in both disease processes by affinity chromatography so that we may purify the antibodies for studies of complement mediated damage, gene isolation and IEM studies. Monoclonal antibodies will be produced which will be utilized in all of the studies mentioned above, in addition to further purification of epidermal antigens. Since so little is known concerning the killing of nucleated cells by complement, these two disease processes, with specific cells as targets, offer unique opportunities to study this mechanism.
