Paraneoplastic
pemphigus (PNP) is an autoimmune bullous disease associated with underlying
neoplasms and characterized by
antibodies against
desmoglein 3 (Dsg 3) and
plakins.
Autoantibodies against
desmoglein 3 in sera of patients with PNP have been proven to cause
acantholysis in vivo in neonatal mice. As a member of the plakin family,
autoantibodies against
desmoplakin were detected frequently by immunoprecipitation in the sera of PNP. The recombinant C-terminus of
desmoplakin was expressed and purified to adsorb the specific
autoantibodies against the C-terminus of
desmoplakin. In vitro
dispase-dependent keratinocyte dissociation assay and in vivo
IgG passive transfer into neonatal mice assay were performed, followed by the electronic microscopy examination and TUNEL assay. We found that anti-C terminus of
desmoplakin autoantibodies caused
blisters and
acantholysis in mice skin at a dose-dependent manner. Moreover, dissociated fragments were observed after incubation with the purified
IgG against
desmoplakin, compared with normal human
IgG (P-value =0.0207). The electronic microscopy examination showed the disconnection of
keratin intermediate filaments from desmosomes. Lastly, apoptosis of keratinocytes in the TUNEL assay was all detected in the skins of neonatal mice after injection of the anti-C terminus of
desmoplakin autoantibodies. Taken together, the study suggests that
autoantibodies against the C-terminus of
desmoplakin might be pathogenic in PNP.