PASSIVE TRANSFER OF ANTI-LAMININ-5 ANTIBODIES INDUCES SUBEPIDERMAL BLISTERS IN NEONATAL MICE

Patients with a recently identified subepithelial blistering disease h ave IgG anti-laminin 5 autoantibodies. To determine if such antibodies can be pathogenic in vivo, we developed and characterized rabbit anti -laminin 5 IgG, and passively transferred these antibodies to neonatal mice. Immune rabbit IgG specifically bound human and murine epidermal basement membranes, immunoblotted and immunoprecipitated all laminin 5 subunits from extracts of human and murine keratinocytes, and showed no reactivity to other keratinocyte proteins or epithelial basement m embranes that do not contain laminin 5. Mice (n=29) receiving purified anti-laminin 5 IgG developed, in a dose-related fashion, circulating anti-laminin 5 antibodies, deposits of rabbit IgG and murine C3 in epi dermal basement membranes, and subepidermal blisters of skin and mucou s membranes. No alterations developed in controls (n=14) receiving ide ntical amounts of normal rabbit IgG. Passive transfer of antilaminin 5 (but not control) IgG to neonatal C5- (n=3) or mast cell-deficient (n =3) mice produced subepidermal blisters with the same clinical, histol ogic, and immunopathologic features as those documented in BALB/c mice . These studies establish an animal model of a human blistering diseas e that can be used to define disease mechanisms and treatment modaliti es.