Hereditary consideration of autoimmune disease related gene AIRE on pemphigus diseases and pemphigus -like diseases.

• Project/Area Number: 26860905
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Kyushu University (2015); Kurume University (2014)
• Principal Investigator: NISHIKAWA Ryuhei 九州大学, (連合)農学研究科(研究院), 学術研究員 (30534531)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: Early endosome antigen 1 / EEA1 / 天疱瘡 / 自己免疫疾患 / BIOCHIP / auto-antibody / pemphigus disease / autoimmune disease / EEA-1

Outline of Final Research Achievements

The major antigens of typical pemphigus disease are desmoglein, desmocollins and a plakin proteins. However, there are novel antigen supposed to be studied to classify the pemphigus disease patients. We used immunoblotting using a serum from an atypical autoimmune bullous disease patient to detect autoantibody, which react with unknown 175 kDa protein. Subsequent studies using two-dimensional gel electrophoresis, immunoblotting and mass-spectrometry identified 175 kDa protein as early endosome antigen 1 (EEA1). This finding was confirmed by subsequent immunological studies, including immunofluorescence of skin and cultured keratinocyte and two-dimensional gel immunoblotting with anti-EEA1 monoclonal antibody and absorption studies using EEA1 recombinant protein. We also developed a novel BIOCHIP assay using full length EEA1 cDNA to detect anti-EEA1 antibodies. However, none of 35 pemphigus sera showed anti-EEA1 antibodies in the BIOCHIP assay except the serum from index case patient.

Research Products

• [Journal Article] Anti-early endosome antigen 1 autoantibodies were detected in a pemphigus-like patient but not in the majority of pemphigus diseases. (2016)
  • Author(s): Nishikawa R, Takahashi H, Matsuda M, Imaoka K, Ogawa M, Teye K, Tsuchisaka A, Koga H, Komorowski L, Probst C, Hachiya T, Fritzler MJ, Ishii N, Ohata C, Furumura M, Krol RP, Muro Y, Morita E, Hashimoto T
  • Journal Title: Exp Dermatol Volume: 25 Issue: 5 Pages: 369-371
  • DOI: 10.1111/exd.12981
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Anti-EEA-1 autoantibodies in pemphigus diseases (2014)
  • Author(s): Ryuhei Nishikawa, Hitoshi Takahashi,Mitsuhiro Matsuda,Kaoru Imaoka, Masahiro Ogawa, Kwesi Teye, Atsunari Tsuchisaka, Hiroshi Koga, Lars Komorowski, Christian Probst, Takahisa Hachiya, Marvin J Fritzler, Norito Ishii, Chika Ohata, Minao Furumura, Rafal P. Krol, Yoshinao Muro, Eishin Morita, and Takashi Hashimoto
  • Organizer: Ｓｉｍｐｏｓｉｕｍ ｏｎ Ｉｍｍｕｎｏｌｏｇｙ
  • Place of Presentation: Ｍａｉｎ ｏｆｆｉｃｅ Ｂｕｉｌｄｉｎｇ， Ｃｏｎｆｅｒｅｎｃｅ Ｒｏｏｍｓ ２ ａｎｄ ３ ａｔ Ｋｕｒｕｍｅ Ｕｎｉｖｅｒｓｉｔｙ Ｓｃｈｏｏｌ ｏｆ Ｍｅｄｉｃｉｎｅ
  • Year and Date: 2014-11-14
• [Remarks] 九州大学・農学研究院 生命機能科学部門 システム生物工学講座のホームページ
  • URL: http://www.agr.kyushu-u.ac.jp/lab/crt/
• [Remarks] 久留米大学皮膚細胞生物学研究所のご説明
  • URL: http://www.med.kurume-u.ac.jp/med/hifusaibou/index.html
• [Remarks] 上原記念生命科学研究財団研究報告集 Vol.23
  • URL: https://ueharazaidan.yoshida-p.net/houkokushu/Vol.23/pdf/163_report.pdf
• [Remarks] 久留米大学皮膚細胞生物学研究所のご説明
  • URL: http://www.med.kurume-u.ac.jp/med/derm/hifusaibou.html
• [Remarks] 久留米大学皮膚細胞生物学研究所 業績一覧
  • URL: http://www.med.kurume-u.ac.jp/med/derm/gyouseki%20list.pdf
• [Remarks] 上原記念生命科学財団研究報告集
  • URL: https://ueharazaidan.yoshida-p.net/houkokushu/Vol.23/pdf/163_report.pdf#search='%E6%A9%8B%E6%9C%AC%E9%9A%86+%E8%85%AB%E7%98%8D%E9%9A%8F%E4%BC%B4%E6%80%A7%E5%A4%A9%E7%96%B1%E7%98%A1'