PL2 Subepithelial bullous diseases – dermatoimmunological and molecular basis

Significant advances have recently taken place in our understanding of inherited and acquired subepithelia bullous diseases. Inherited disorders are collectively termed epidermolysis bullosa and include simplex, junctional and dystrophic categories. Elucidation of the structure and function of the basement membrane underlying stratified squamous epithelial tissues has provided a foundation of knowledge, which has permitted application to clinical diseases. Advances in our understanding of the physiological basis for mucosal cohesion and molecular diagnosis of inherited diseases have resulted in the elucidation of DNA mutations, which correlate with the molecular pathology. Current preclinical efforts in this field are largely directed at development of a specific and effective molecular therapy and several approaches will be discussed. The molecular etiology of the development of squamous cell carcinoma in a subset of dystrophic EB patients has also been recently elucidated and will be discussed. Acquired subepithelial bullous disorders are becoming better understood as well, through the development of several preclinical animal models, including models for bullous pemphigoid and epidermolysis bullosa acquisita. Autoantibodies in each of these diseases appear to require complement and other local immune components, in contrast to pemphigus antibodies, which appear to be pathogenic themselves. In particular, bullous pemphigoid blister formation shows reliance on metaloproteinase expressed by immune cells, suggesting new targets for molecular therapy.