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.