THE MEMBERS OF THE PLAKIN FAMILY OF PROTEINS RECOGNIZED BY PARANEOPLASTIC PEMPHIGUS ANTIBODIES INCLUDE PERIPLAKIN

Sera of patients with paraneoplastic pemphigus (PNP) characteristicall y immunoprecipitate five proteins, observations confirmed with the ser a examined in this study. The proteins characterized thus far as autoa ntigens in PNP all belong to the plakin family of proteins and include desmoplakin, the 230 kDa bullous pemphigoid antigen, and envoplakin. The pattern of bands precipitated from metabolically labeled human ker atinocyte extracts by each PNP serum was different, suggesting varying titers of antibodies against unique epitopes in various plakin family members. To further characterize this PNP antibody response, we produ ced fusion proteins of the homologous tail region of five plakin famil y members, including the recently cloned periplakin, Immunoblotting of equal amounts of each plakin tail-glutathione S-transferase fusion pr otein with PNP sera revealed a strong reaction with the envoplakin tai l domain. Each sera also recognized periplakin, and certain sera recog nized desmoplakin and plectin, and, weakly, bullous pemphigoid antigen 1. PNP sera were affinity purified with periplakin and envoplakin tai l fusion proteins. Immunoprecipitation and immunoblotting with these a ffinity purified antibodies revealed shared as well as unique epitopes in the tail domains of these plakins. This study indicates that a hom ologous region in the carboxy-terminus of plakins, including the newly characterized periplakin, serves as an antigenic site in PNP.