Fab fragments directed against laminin 5 induce subepidermal blisters in neonatal mice. Clin Immunol 2000 Apr;95(1 Pt 1):26-32
Date
05/04/2000Pubmed ID
10794429DOI
10.1006/clim.2000.4845Scopus ID
2-s2.0-0034040623 (requires institutional sign-in at Scopus site) 50 CitationsAbstract
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.
Author List
Lazarova Z, Hsu R, Briggaman RA, Yancey KBMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Newborn
Basement Membrane
Cell Adhesion Molecules
Disease Models, Animal
Immunoglobulin Fab Fragments
Immunoglobulin G
Mice
Mice, Inbred BALB C
Mice, Inbred DBA
Pemphigoid, Benign Mucous Membrane
Skin
