We have recently identified patients with a form of
cicatricial pemphigoid who have
IgG anti-basement membrane
autoantibodies directed against
epiligrin, a
laminin isoform closely related if not identical to
laminin 5. These patients'
autoantibodies bind the lower lamina lucida of human epidermal basement membrane and immunoprecipitate this
laminin isoform from extracts and media of biosynthetically radiolabeled human keratinocytes. Immunoblot studies show that these patients'
autoantibodies specifically bind the alpha subunit of this
laminin (i.e.,
laminin subunit alpha 3). We have found no evidence of these
autoantibodies in normal volunteers or patients with other
bullous skin diseases (including those with other forms of CP). These studies have identified a group of patients with an acquired, autoimmune, subepidermal bullous disorder who have disease-specific
autoantibodies directed against the alpha subunit of
epiligrin/
laminin 5. These findings correlate with prior reports showing that a
monoclonal antibody directed against this
laminin subunit induces detachment of keratinocytes from extracellular matrix in vitro as well as epidermis from human skin in situ. Together, these findings suggest that this
laminin mediates attachment of basal keratinocytes to epidermal basement membrane and that
autoantibodies directed against it may be pathogenic. Moreover, recent studies showing that subunits of this
laminin isoform are mutated in some patients with Herlitz's
junctional epidermolysis bullosa indicate that acquired or inherited abnormalities in this adhesion
ligand are associated with
skin diseases characterized by separation of epidermis from epidermal BM.