Mucous membrane
pemphigoid (
MMP) (also known as
cicatricial pemphigoid) is a rare autoimmune mucocutaneous blistering disease that affects mucous membranes derived from stratified squamous epithelium and the skin. A subset of
MMP affects only the oral cavity and is referred to as the oral
pemphigoid (OP).
MMP and OP are characterized by subepithelial vesicles on histology and in vivo deposition of
immunoglobulins and
complement at the basement membrane zone (BMZ) on immunopathology. Previous studies have shown that sera of patients with
MMP bind to human
integrin beta4, while sera of patients with oral
pemphigoid bind to the
integrin alpha6 component of the heterodimer. The prognosis in
MMP is grave but excellent in OP. In this study we compare the binding of sera from patients with OP from Boston, MA, USA to Naples, Italy, and attempt to identify an
epitope to which the anti-
integrin alpha6 human
autoantibody binds. Our results indicate that the sera from Boston and Naples are identical in their reactivity. They recognize a fragment I (AA 23-462) and its subfragment IB (AA 217-462) only, in the human
integrin alpha6 molecule. Blocking studies, immunoprecipitation and immunoabsorbtion studies confirm the presence of this single 245 AA region.
Antibodies to subfragment IB cause BMZ separation in organ culture using normal human oral mucosa as substrate. This preliminary study indicates that patients on both continents may have similar reactivity and suggests that an intercontinental study group could be established to advance our understanding of the pathogenesis of OP and the biology of anti-alpha6
integrin autoantibodies.