The interaction of pemphigus autoimmunoglobulins with epidermal cells: activation of the fas apoptotic pathway and the use of caspase activity for pathogenicity tests of pemphigus patients.

Abstract

Pemphigus is a fatal autoimmune disease in which autoimmunoglobulins PV-IgG (binding to desmoglein 3) and PF-IgG (binding to desmoglein 1) in pemphigus vulgaris and pemphigus foliaceus, respectively, cause intraepidermal blisters, cell-cell separation (acantholysis), and cell death. The mechanism of acantholytic lesion formation has not yet been elucidated. Recently, we have reported that an apoptotic mechanism might be operative in PV-IgG-induced acantholysis: (1) in patients' lesional and some perilesional skin portions, the FasR pathway is activated as its components were enriched; (2) in cultured keratinocytes, PV-IgG upregulates effectors of the FasR pathway (including the mitochondrial loop), as found by immunodetermination (cytochemistry, Western blot of pathway effectors) and determination of caspases 1, 3, and 8 activity/activation; (3) in organ cultures of skin incubated with PV-IgG, activated caspase 8 was found also in perilesional cells and coaggregated with bound PV-IgG; (4) caspase 8 activation in DISCs precedes caspase 3 activation in keratinocytes in cultures upon incubation with PV-IgG. Because caspase activation was shown to accompany lesion formation in cell and organ cultures incubated with PV-IgG, we used caspase activity to monitor the pathogenicity of PV-IgG in relation to PV-IgG binding to epithelia. A rough correlation was found between sera titers, determined by IIF and by immunoblot binding to desmoglein 3, and activation of caspase 3.

• Authors: Marina Frusic-Zlotkin, Rochel Pergamentz, Beno Michel, Michael David, Daniel Mimouni, François Brégégère, Yoram Milner
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1050 Pg. 371-9 (Jun 2005) ISSN: 0077-8923 [Print] United States
• PMID: 16014554 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Caspase Inhibitors
• Immunoglobulin G
• Caspases

Topics

• Acantholysis (immunology)
• Apoptosis (immunology)
• Autoantibodies (immunology)
• Autoimmunity
• Blotting, Western
• Caspase Inhibitors
• Caspases (metabolism)
• Cells, Cultured
• Enzyme Activation
• Epidermis (immunology)
• Fluorescent Antibody Technique, Indirect
• Humans
• Immunoglobulin G
• Keratinocytes (enzymology, immunology, metabolism)
• Kinetics
• Organ Culture Techniques
• Pemphigus (immunology)
• Signal Transduction (immunology)