Paraneoplastic pemphigus sera react strongly with multiple epitopes on thevarious regions of envoplakin and periplakin, except for the C-terminal homologous domain of periplakin

Paraneoplastic pemphigus sera react with multiple plakin family proteins, a mong which only envoplakin and periplakin are constantly detected by immuno blotting using normal human epidermal extracts. Using bacterial expression vectors containing polymerase chain reaction-amplified cDNA, we have prepar ed variously truncated recombinant glutathione-S-transferase-fusion protein s of envoplakin and periplakin, which presented N-terminal, central and C-t erminal domains of each protein, as well as the so-called C-terminal homolo gous domain of envoplakin and the junctional regions of these domains. By i mmunoblotting using these 11 recombinant proteins, we demonstrated that mos t of the 26 paraneoplastic pemphigus sera reacted very strongly with multip le recombinant proteins of envoplakin and periplakin, except for the C-term inal homologous domain of periplakin, We also examined the reactivity with these recombinant proteins of other blistering diseases, including pemphigu s vulgaris, pemphigus foliaceus, and bullous pemphigoid, and found that a f ew nonparaneoplastic pemphigus sera showed a weak reactivity with some of t he recombinant proteins. Interestingly, some sera showed relatively strong reactivity with the C-terminal homologous domain of periplakin to which par aneoplastic pemphigus sera reacted less frequently. These results indicate that, although nonparaneoplastic pemphigus sera occasionally show a weak re activity with envoplakin and periplakin, the pathogenicity and the mechanis m of antibody production in these cases may be different from those in para neoplastic pemphigus.