detailed characterization of autoantibodies in paraneoplastic pemphigus by phage display

• Project/Area Number: 23591628
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Toho University (2012-2013); Teikyo University (2011)
• Principal Investigator: ISHII Ken 東邦大学, 医学部, 准教授 (50296670)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 皮膚科学 / 自己免疫性疾患 / 細胞接着 / 自己免疫 / 天疱瘡 / 自己抗体

Research Abstract

To study the pathogenic mechanism of pareneoplastic pemphigus(PNP), we used phage display to clone monoclonal anti-Dsg3 antibodies from a PNP patient. We isolated 20 unique Dsg3-reactive mAbs, which we classified into four groups according to amino acid sequence. Pathogenic assay showed that three antibodies displayed pathogenic activity in blister formation with different potencies. Epitope mapping showed that these pathogenic mAbs bound Ca(2+)-dependent conformational epitopes in the middle portion of the extracellular region of Dsg3. These mAbs reflect the unique polyclonal nature of anti-Dsg3 antibodies in PNP and represent an important tool for detailing the pathophysiological mechanisms of blister formation in PNP.

Research Products

• [Journal Article] Sporadic VACTERL association in a Japanese family with Sjogren-Larsson syndrome. (2013)
  • Author(s): Takeichi T, Sugiura K, Arai H, Ishii K, Kono M, Akiyama M.
  • Journal Title: Acta Dermato-Venereol Volume: 93 Issue: 5 Pages: 579-580
  • DOI: 10.2340/00015555-1526
  • Peer Reviewed
• [Journal Article] Functional tight junction barrier localizes in the second layer of the stratum granulosum of human epidermis (2013)
  • Author(s): Yoshida K, Yokouchi M, Nagao K, Ishii K, Amagai M, Kubo A
  • Journal Title: J Dermatol Sci Volume: 71 Issue: 2 Pages: 89-99
  • DOI: 10.1016/j.jdermsci.2013.04.021
  • Peer Reviewed
• [Journal Article] In vitro pathogenicity assay for anti-desmoglein autoantibodies in pemphigus (2013)
  • Author(s): Ishii, K.
  • Journal Title: Methods Mol Biol Volume: 961 Pages: 219-225
  • DOI: 10.1007/978-1-62703-227-8_13
  • ISBN: 9781627032261, 9781627032278
  • Peer Reviewed
• [Journal Article] Pathogenic anti-desmoglein 3 mAbs cloned from a paraneoplastic pemphigus patient by phage display (2012)
  • Author(s): Saleh MA, Ishii K, Yamagami J, Shirakata Y, Hashimoto K, Amagai M
  • Journal Title: J Invest Dermatol Volume: 132(4) Issue: 4 Pages: 1141-1148
  • DOI: 10.1038/jid.2011.449
  • Peer Reviewed
• [Journal Article] Development of NC1 and NC2 domains of type VII collagen ELISA for the diagnosis and analysis of the time course of epidermolysis bullosa acquisita patients (2011)
  • Author(s): Saleh MA
  • Journal Title: J Dermatol Sci Volume: 62 Issue: 3 Pages: 169-175
  • DOI: 10.1016/j.jdermsci.2011.03.003
  • Peer Reviewed
• [Presentation] 喉頭粘膜病変を主症状とした抗ラミニン332型粘膜類天疱瘡の1例 (2013)
  • Author(s): 市村知佳、陳怡如、高田裕子、石井健、峯村佐和子、石井文人、橋本隆、石河晃
  • Organizer: 第35会水疱症研究会
  • Place of Presentation: 大分
• [Presentation] 骨髄異形成症候群に合併した抗p200類天疱瘡の1例 (2012)
  • Author(s): 小原芙美子,橋本由起,漆畑真理,鷲崎久美子,石井健,関東裕美,石河晃
  • Organizer: 第34回水疱症研究会
  • Place of Presentation: 青森
  • Year and Date: 2012-10-06
• [Presentation] Analysis of epitope profile of autoantibodies in pemphigus vulgaris using domain-swapped Dsg3/Dsg2 ELISAs (2012)
  • Author(s): Saleh M, Ken Ishii, Jun Yamagami, Takahisa Hachiya, Masayuki Amagai
  • Organizer: 42nd Annual European Society of Dermatology Research Meeting
  • Place of Presentation: Venice, Italy
• [Presentation] What's new in bullous disease? What's new session (2011)
  • Author(s): Ishii K
  • Organizer: 22nd World Congress of Dermatology
  • Place of Presentation: Seoul Korea
• [Presentation] Human epidermal tight junctions are functional and allow penetration of activated Langerhans cell dendrites (2011)
  • Author(s): Yoshida K, Kubo A, Yokouchi M, Ishii K, Kawasaki H, Ebihara T, Ohyama M, Nagao K, Amagai M
  • Organizer: 71th Annual meeting for The Society For Investigative Dermatology
  • Place of Presentation: Phoenix
• [Presentation] What’s new in bullous disease? (2011)
  • Author(s): Ishii K
  • Organizer: 22nd World Congress of Dermatology(招待講演)
  • Place of Presentation: 韓国、ソウル
• [Presentation] Analysis of epitope profile of autoantibodies in pemphigus vulgaris using domain-swapped Dsg3/Dsg2 ELISAs
  • Author(s): Saleh M, Ken Ishii, Jun Yamagami, Takahisa Hachiya, Masayuki Amagai
  • Organizer: 42nd Annual European Society of Dermatology Research Meeting
  • Place of Presentation: イタリア、ベニス
• [Book] In vitro pathogenicity assay for anti-desmoglein autoantibodies in pemphigus. Molecular Dermatology Methods and Protocols Methods Mol Biol. Vol. 961 (2013)
  • Author(s): Ishii K, Amagai M
  • Publisher: Springer Science