Antibody-induced proteinase activation: a proposed mechanism for pemphigus

The current state of understanding of pemphigus includes the following: 1. Pemphigus is an autoimmune disease. In all variants a circulating autoantibody is found which binds to epidermal cells. In vivo antibody may be found deposited in the epidermis of patients. 2. The autoantibody levels generally correlate with disease activity indicating a relationship between antibody and clinical disease. 3. Although complement components are found in lesional skin, complement does not appear to be necessary for dissolution of the epidermal cement substance. 4. The treatment of pemphigus with corticosteroids has drastically reduced mortality rates. 5. Three different groups have presented results in two different experimental systems which indicate that subsequent to binding of pemphigus antibody to epidermal cells a proteinase is activated. This proteinase(s) degrades the intercellular cement substance of epidermis which results in loss of cellular adhesion and acantholysis. There are numerous questions still remaining. What is the nature of the proteinase(s) and the surface protein(s) it cleaves? Does the binding of pemphigus antibody to the cell surface induce enzyme synthesis, specific enzyme activation, or generalized lysosomal secretion? The answers to these questions will have broad biologic relevance since they may elucidate the role of anticell surface antibodies in disease states.