Intraepidermal and dermal-epidermal cohesion are of paramount importance for the integrity of the skin. Some constituent molecules of keratinocyte adhesion complexes and basement membrane-associated structures are the targets of antibody-mediated autoimmune reactions that give rise to various (muco-)cutaneous blistering diseases. The current state of our knowledge about these molecules--along with the main clinical, histological, and immunohistochemical features of the corresponding
autoimmune diseases and their pathogenetic mechanisms--comprise the subjects surveyed in this review. Among the
desmosomal cadherins (
desmogleins and
desmocollins) that mediate epidermal cell-cell adhesion, it has been demonstrated that
desmoglein 1 and
desmoglein 3 are the
autoantigens of
pemphigus foliaceus and
pemphigus vulgaris, respectively, both diseases that result in intraepidermal blistering. Further,
desmocollin autoantibodies may be involved in
IgA pemphigus. Paraneoplastic
pemphigus is associated with
autoantibodies directed against the desmosomal plaque
protein,
desmoplakin. Of the constituents of hemidesmosomes, the plaque
protein, BP230 (BPAG1), and the
collagen-like transmembrane
protein, BP180 (BPAG2), are the
autoantigens of
bullous pemphigoid and
pemphigoid gestationis, the manifestations of both of which include subepidermal blistering. Several diseases arise from autoimmune reactions against certain
proteins associated with the basement membrane located beneath hemidesmosomes, for example
laminin 5 (
cicatricial pemphigoid), ladinin (LAD-1; linear
IgA disease),
uncein, and
collagen VII (
epidermolysis bullosa acquisita), the last of which is the constituent
protein of the anchoring fibrils. Such recent advances in the elucidation of the molecular nature of
autoantigens may serve as the basis for the development of novel molecule-based therapeutic strategies.