Epiplakin Is a Paraneoplastic Pemphigus Autoantigen and Related to Bronchiolitis Obliterans in Japanese Patients

Atsunari Tsuchisaka, Sanae Numata, Kwesi Teye, Yohei Natsuaki, Tamihiro Kawakami, Yoshito Takeda, Wenqing Wang, Kazushi Ishikawa, Mizuki Goto, Hiroshi Koga, Ryosuke Sogame, Norito Ishii, Shinzo Takamori, Tomoaki Hoshino, Oliver Brandt, Hendri H. Pas, Sakuhei Fujiwara, Takashi Hashimoto*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

All plakin family proteins are known to be autoantigens in paraneoplastic pemphigus (PNP). In this study, we first examined whether PNP sera also react with epiplakin, another plakin protein, by various immunological methods using 48 Japanese PNP sera. Immunofluorescence confirmed that cultured keratinocytes expressed epiplakin. Epiplakin was detected by 72.9% of PNP sera by immunoprecipitation-immunoblotting with KU-8 cell extract, but not by immunoblotting of either normal human epidermal extract or KU-8 cell extract. Epiplakin was essentially not detected by 95 disease and normal control sera. Statistical analyses of various clinical and immunological findings revealed a significant correlation of the presence of anti-epiplakin antibodies with both bronchiolitis obliterans and mortality. No epiplakin-negative PNP case developed bronchiolitis obliterans. However, although 29.4% of European patients with PNP had bronchiolitis obliterans, significant correlation with anti-epiplakin autoantibodies was not observed. In further studies for lung, immunofluorescence showed the presence of epiplakin in normal human lung, particularly respiratory bronchiole, immunoprecipitation-immunoblotting showed that PNP sera reacted with epiplakin in cultured lung cells, and mice injected with polyclonal antibody specific to epiplakin histopathologically showed abnormal changes in small airway epithelia. These results indicated that epiplakin is one of the major PNP autoantigens and is related to PNP-related bronchiolitis obliterans.

Original languageEnglish
Pages (from-to)399-408
Number of pages10
JournalJournal of Investigative Dermatology
Volume136
Issue number2
DOIs
Publication statusPublished - Feb-2016

Keywords

  • AUTOIMMUNE MULTIORGAN SYNDROME
  • HUMAN EPIDERMAL AUTOANTIGEN
  • PLAKIN FAMILY
  • DESMOGLEIN 3
  • IN-VIVO
  • AUTOANTIBODIES
  • IDENTIFICATION
  • PERIPLAKIN
  • VULGARIS
  • MEMBER

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