Acquired skin disease of hemidesmosomes

The hemidesmosome is a membrane-associated supramolecular dermal epidermal complex linking the cytoskeleton of the basal keratinocyte to structures within the papillary dermis. Different components of this complex have been identified as autoantigens in autoimmune bullous skin diseases. Some of the autoantigens have been characterized at the molecular level. Little is known, however, about the factors that initiate the production of autoantibodies. By histopathology, acquired skin diseases of hemidesmosomes show subepidermal blisters and by direct immunofluorescence, linear deposits of IgG, C3 or IgA at the dermal epidermal junction. Bullous pemphigoid (BP) is the most common acquired disease of hemidesmosomes. Two proteins, BP180 and BP230, have been identified as primary targets of autoantibodies in BP. In addition, pemphigoid/herpes gestationis, lichen planus pemphigoides, cicatricial pemphigoid and linear IgA disease are characterized by an immune response to BP180. Laminin 5 is another well-characterized anchoring filament-lamina densa component of hemidesmosomes. Patients with autoantibodies to laminin 5 show the clinical phenotype of cicatricial pemphigoid. Other acquired skin diseases of the hemidesmosomes reveal autoantibodies to a plectin-like protein, the beta4 subunit of alpha6beta4 integrin, uncein and a not yet characterized 168 kDa protein. Recently, diseases with autoantibodies to 105 and 200 kDa proteins of the lower lamina lucida have been reported. The association of these autoantigens with hemidesmosomes still needs to be demonstrated. Finally, anchoring fibrils associate with the dermal epidermal anchoring complex. The major structural component of anchoring fibrils is type VII collagen, the autoantigen of epidermolysis bullosa acquisita.