Passive transfer of anti-laminin 5 antibodies induces subepidermal blisters in neonatal mice

Zelmira Lazarova, Carole Yee, Thomas Darling, Robert A. Briggaman, Kim B. Yancey

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1509-1518
Number of pages10
JournalJournal of Clinical Investigation
Volume98
Issue number7
StatePublished - Oct 1 1996

Fingerprint

Blister
Immunoglobulin G
Antibodies
Basement Membrane
Rabbits
Keratinocytes
kalinin
Mast Cells
Autoantibodies
Mucous Membrane
Animal Models
Skin
Proteins

Keywords

  • animal models
  • autoimmunity
  • laminin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Passive transfer of anti-laminin 5 antibodies induces subepidermal blisters in neonatal mice. / Lazarova, Zelmira; Yee, Carole; Darling, Thomas; Briggaman, Robert A.; Yancey, Kim B.

In: Journal of Clinical Investigation, Vol. 98, No. 7, 01.10.1996, p. 1509-1518.

Research output: Contribution to journalArticle

Lazarova, Zelmira ; Yee, Carole ; Darling, Thomas ; Briggaman, Robert A. ; Yancey, Kim B. / Passive transfer of anti-laminin 5 antibodies induces subepidermal blisters in neonatal mice. In: Journal of Clinical Investigation. 1996 ; Vol. 98, No. 7. pp. 1509-1518.
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