[Cellular adhesion molecules and components of the extracellular matrix as target structures of autoimmunity]

Cell-cell and cell-matrix adhesion molecules as well as extracellular matrix components are target structures of antibody-mediated autoimmunity that have recently been well characterized at the molecular biological level. Pathogenic autoantibodies against these molecules are causally related to disturbances of cell and tissue adhesion that become apparent as various (muco-)cutaneous blistering diseases. Desmosomal cadherins (desmogleins and desmocollins) mediate epidermal intercellular adhesion. Among these, desmoglein 1 and desmoglein 3 are the autoantigens of pemphigus foliaceus and pemphigus vulgaris, respectively, exhibiting intraepidermal blistering. The pathogenic relevance of autoantibodies against desmocollins. (IgA pemphigus) and desmoplakins (paraneoplastic pemphigus) still remains unclear. Hemidesmosomes contain the plaque protein BPAG1 and the partly collagen-like transmembrane protein BPAG2, representing the autoantigens of bullous pemphigoid and pemphigoid gestationis with subepidermal blistering. A certain subtype of cicatricial (benign mucous membrane) pemphigoid is characterized by autoantibodies against laminin 5 present in the subhemidesmosomal anchoring filaments, while epidermolysis bullosa acquisita and bullous SLE exhibit autoantibodies against collagen type VII constituting the anchoring fibrils. In addition, autoantibodies against a particular collagen type IV chain of the glomerular basement membrane are responsible for the manifestation of Goodpasture's syndrome. These recent molecular biological findings might be the basis for the development of novel therapeutic strategies.