Passive transfer of anti-laminin 5 antibodies induces subepidermal blisters in neonatal mice.
Patients with a recently identified subepithelial blistering disease have 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 membranes 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 epidermal basement membranes, and subepidermal blisters of skin and mucous membranes. No alterations developed in controls (n = 14) receiving identical amounts of normal rabbit IgG. Passive transfer of anti-laminin 5 (but not control) IgG to neonatal C5- (n = 3) or mast cell-deficient (n = 3) mice produced subepidermal blisters with the same clinical, histologic, and immunopathologic features as those documented in BALB/c mice. These studies establish an animal model of a human blistering disease that can be used to define disease mechanisms and treatment modalities.
Lazarova
Z
Z
Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Yee
C
C
Darling
T
T
Briggaman
R A
RA
Yancey
K B
KB
D000818:Animals; D000831:Animals, Newborn; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D001485:Basement Membrane / Q000473:pathology; D001768:Blister / Q000209:etiology / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D004195:Disease Models, Animal; D004817:Epidermis / Q000473:pathology; D007116:Immunization, Passive; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008811:Mice, Inbred DBA; D010390:Pemphigoid, Benign Mucous Membrane / Q000209:etiology / Q000276:immunology*; D011817:Rabbits; D012867:Skin / Q000473:pathology; D013045:Species Specificity; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D000097794:Kalinin