Pemphigus vulgaris (PV) is an autoimmune disease characterized by
mucocutaneous intraepithelial blisters and pathogenic autoantibodies against
desmoglein 3. The mechanism of blister formation in pemphigus has not been
defined; however, in vitro data suggest a role for activation of intracellular
signalling cascades. OBJECTIVES: To investigate the contribution of these
signalling pathways to the mechanism of PV IgG-induced acantholysis in vivo.
METHODS: We used the passive transfer mouse model. Mice were injected with IgG
fractions of sera from a patient with PV, with or without pretreatment with
inhibitors of proteins that mediate intracellular signalling cascades. RESULTS:
Inhibitors of tyrosine kinases, phospholipase C, calmodulin and the
serine/threonine kinase protein kinase C prevented PV IgG-induced acantholysis in
vivo. CONCLUSIONS: These observations strongly support the role of intracellular
signalling cascades in the molecular mechanism of PV IgG-induced acantholysi
