Patients with one form of
cicatricial pemphigoid have
IgG autoantibodies directed against
laminin 5 (alpha3beta3gamma2), an adhesion
protein in epidermal basement membrane. Anti-
laminin 5 autoantibodies are not found in patients with other skin or mucosal diseases and hence serve as a specific marker for this autoimmune blistering disorder. The demonstration that experimental and patient anti-
laminin 5 IgG are pathogenic in animal models indicated that such
autoantibodies are central to disease pathophysiology. To investigate further the role of antibody valence and
complement in triggering lesion formation in vivo, rabbit anti-
laminin 5 (or normal, control)
Fab fragments were passively transferred to neonatal BALB/c mice. Mice receiving anti-
laminin 5 Fab fragments developed, in a dose-related fashion, circulating anti-basement membrane
antibodies, deposits of immunoreactive rabbit
IgG (but not murine C3) in epidermal basement membranes, and subepithelial
blisters of skin and mucous membranes. Such alterations were not observed in mice treated with equivalent concentrations of normal rabbit
Fab fragments. These studies demonstrated that neither complement activation nor cross-linking of
laminin 5 in epidermal basement membranes was required for induction of subepidermal
blister formation in this animal model of a human autoimmune bullous disease.