Serum plakophilin-3 autoreactivity in paraneoplastic pemphigus

Paraneoplastic pemphigus (PNP) is a malignancy-associated autoimmune disease in which circulating autoantibodies recognize various polypeptides that constitute the desmosomes and hemidesmosomes of epithelial structures.

To determine whether PNP is associated with autoreactivity against the armadillo-repeat-containing plakophilin-3 (PKP3) protein.

HEK293 cells were transiently transfected with either a pEF6/myc-His or a pEGFP-N2 construct, both encoding human PKP3 (protein products of 85 kDa and 115 kDa, respectively). Protein lysates were made in Laemmli buffer. The proteins were separated by gel electrophoresis, transferred to filters and probed with five PNP sera, four pemphigus vulgaris sera, two pemphigus foliaceus sera, five bullous pemphigoid sera, one cicatricial pemphigoid serum and one linear IgA dermatosis serum. A mouse monoclonal anti-PKP3 antibody raised against a 20-amino acid peptide of human PKP3 was used as a positive control.

Autoreactivity against both 85-kDa and 115-kDa recombinant PKP3 protein products was detected in all five PNP sera and in one pemphigus vulgaris serum. None of the sera of patients with basement membrane zone bullous diseases reacted with the PKP3 protein products. The presence of autoantibodies against PKP3 in PNP sera was subsequently confirmed in human epidermal lysate blots.

This is the first report of PKP3 reactivity in bullous disorders, which was present in all the PNP sera tested. The presence of PKP3 reactivity in one patient with pemphigus vulgaris is not unexpected as the desmosome is also targeted in this disease.