Fab fragments directed against laminin 5 induce subepidermal blisters in neonatal mice

Zelmira Lazarova, Roger Hsu, Robert A. Briggaman, Kim B. Yancey

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Patients with the form of cicatricial pemphigoid have IgG autoantibodies directed against laminin 5 (α3β3γ2), 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 rabbi 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. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)26-32
Number of pages7
JournalClinical Immunology
Volume95
Issue number1 I
DOIs
StatePublished - Apr 2000

Keywords

  • Animal model
  • Autoimmunity
  • Basement membrane
  • Bullous disease

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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