Passive transfer of anti-laminin 5 antibodies induces subepidermal blisters in neonatal mice. J Clin Invest 1996 Oct 01;98(7):1509-18
Date
10/01/1996Pubmed ID
8833897Pubmed Central ID
PMC507581DOI
10.1172/JCI118942Scopus ID
2-s2.0-0029816287 (requires institutional sign-in at Scopus site) 166 CitationsAbstract
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.
Author List
Lazarova Z, Yee C, Darling T, Briggaman RA, Yancey KBMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Newborn
Autoimmune Diseases
Basement Membrane
Blister
Cell Adhesion Molecules
Disease Models, Animal
Epidermis
Immunization, Passive
Mice
Mice, Inbred BALB C
Mice, Inbred DBA
Pemphigoid, Benign Mucous Membrane
Rabbits
Skin
Species Specificity
