The general and long-term goal of my laboratory is to study autoantibody-mediated skin diseases in order to further our understanding not only of the pathophysiology of these diseases but also of the structure and function of normal epidermis and epidermal basement membrane zone. Specifically, antibodies in these diseases define molecules in the normal epidermis. We have characterized the antigens defined by three of these diseases: bullous pemphigoid (BP), pemphigus vulgaris (PV), and pemphigus foliaceus (PF). We have defined the cells which synthesize these antigens, as well as the antigen defined by the autoantibodies found in patients with epidermolysis bullosa acquisita (EBA). We have used the binding of antibodies to specific molecules to make diagnoses of BP, EBA, PV or PF in various complicated cases of these diseases. We have also used antibodies to BP antigen, as well as to other basement membrane components, to rapidly diagnose various types of epidermolysis bullosa, often within the first few days after birth. We have demonstrated that autoantibodies from patients with fogo selvagem, a form of pemphigus endemic to Brazil, have similar specificities to autoantibodies from patients with sporadic North American PF. We have used autoantibodies from these bullous disease patients to help define stages of differentiation of keratinocytes. Specifically, the synthesis of BP and PV antigens are normally modulated, along with differentiation, by extracellular calcium concentration in culture. In virus sarcoma infected cells, this modulation goes awry. Finally, we are just beginning to try to characterize some of these antigens defined by these autoimmune diseases at the gene level.