Bullous pemphigoid antigens

The bullous pemphigoid (BP) antigen(s) is a normal component of the basement membrane zone (BMZ) of skin and other stratified squamous epithelia and is defined by its interaction with autoantibodies present in the sera of patients with BP, as demonstrated by immunofluorescent (IF) techniques. The precise physiological function and the biochemical characterization of the BP antigen remain unclear. BP autoantibodies have been recently shown to be pathogenic in vitro and in vivo. They promote neutrophil recruitment to the BMZ by complement activation and reproduce subepithelial vesiculation, the hallmark of the human disease. As a consequence of these findings, the characterization of the BP antigen(s) is crucial in studies dealing with pathogenetic mechanisms operating in the disease. The localization of the BP antigen has been studied previously, using both immunofluorescence (IF) and immunoelectron microscopic techniques (immuno-EM), Using standard indirect IF, employing sera from patients with BP, it is established that BP antibodies bind the BMZ, producing a linear pattern of fluorescence on vertical sections of squamous epithelium. Direct and indirect im-muno-EM using immunoperoxidase techniques have shown that BP autoantibodies in vitro are deposited within the lamina lucida of the BMZ, in close apposition to the basal cell plasma membrane. This would imply that the BP antigen is located there as well. We have made a series of experimental observations performed both on intact epidermis and on basal cell suspensions, which show that, contrary to previous assumptions, the majority of the BP antigen is intracellular, closely associated with the basal cell hemidesmosome and only a small portion of it is extracellular in the lamina lucida. In view of these results we must reconsider our concepts of the in situ localization of the BP antigen(s). Previous immunoblotting and immunoprecipitation studies identified only one antigen (a doublet with an estimated MW of 220 kD to 240 kD). In a recent study we report that a group of 28 BP sera recognize up to 5 different polypeptide chains in epidermal extracts by immunoblotting procedures, with individual sera recognizing different sets of these polypeptide chains. Therefore, different BP patients may have various sets of autoantibodies that are defined by the antigens with which they react. It will now be essential to determine the relationship of the 5 proteins reactive with BP sera by immunoblotting in epidermal extracts with the structural components of the basal cell hemides-mosome.