Development of new objective methods to assess disease activity in pemphigus using monoclonal single-chain- variable-fragment antibodies

• Project/Area Number: 20591328
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Keio University
• Principal Investigator: ISHII Ken Keio University, 医学部, 准教授 (50296670)
• Co-Investigator(Kenkyū-buntansha): 久保 亮治 慶應義塾大学, 医学部, 講師 (70335256) ; 天谷 雅行 慶應義塾大学, 医学部, 教授 (90212563)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 皮膚科学 / 皮膚診断学 / 自己免疫性疾患

Research Abstract

In order to develop new objective methods to assess the disease activity in pemphigus, we performed the detailed characterization of repertories of monoclonal anti-desmoglein (Dsg) 1 autoantibodies isolated from a pemphigus foliaceus patient by phage display. Major epitopes on desmoglein bound by autoantibodies in many pemphigus patients were uncovered. The reactivity against the epitopes by pemphigus sera correlates with the disease activity. These findings will facilitate the development of new objective methods to assess the disease activity in pemphigus patients.

Research Products

• [Journal Article] Homologous regions of autoantibody heavy chain complementarity-determining region 3 (H-CDR3) in patients with pemphigus cause pathogenicity (2010)
  • Author(s): Yamagami J, Payne AS, Kacir S, Ishii K, Siegel DL, Stanley JR
  • Journal Title: J Clin Invest. 120(11) Pages: 4111-7
  • Peer Reviewed
• [Journal Article] Immune response towards amino-terminus of desmoglein 1 prevails across different activity stages in nonendemic pemphigus foliaceus (2010)
  • Author(s): Chan PT, Ohyama B, Nishifuji K, Yoshida K, Ishii K, Hashimoto T, Amagai M
  • Journal Title: Br J Dermatol. 162(6) Pages: 1242-50
  • Peer Reviewed
• [Journal Article] Immune response towards amino-terminus of desmoglein 1 prevails across different activity stages in nonendemic pemphigus foliaceus. (2010)
  • Author(s): Chan P.T.
  • Journal Title: Br J Dermatol. Volume: 162 Pages: 1242-50
  • Peer Reviewed
• [Journal Article] Homologous regions of autoantibody heavy chain complementarity-determining region 3 (H-CDR3) in patients with pemphigus cause pathogenicity. (2010)
  • Author(s): Yamagami J.
  • Journal Title: J Clin Invest. Volume: 120 Pages: 4111-7
  • Peer Reviewed
• [Journal Article] Antibodies to the desmoglein 1 precursor proprotein but not to the mature cell surface protein cloned from individuals without pemphigus (2009)
  • Author(s): Yamagami J, Kacir S, Ishii K, Payne AS, Siegel DL, Stanley JR
  • Journal Title: J Immunol. 183(9) Pages: 5615-21
  • Peer Reviewed
• [Journal Article] Pathogenic epitopes of autoantibodies in pemphigus reside in the amino-terminal adhesive region of desmogleins which are unmasked by proteolytic processing of prosequence (2009)
  • Author(s): Yokouchi M, Saleh MA, Kuroda K, Hachiya T, Stanley JR, Amagai M, Ishii K
  • Journal Title: J Invest Dermatol. 129 Pages: 2156-216
  • Peer Reviewed
• [Journal Article] Pathogenic epitopes of autoantibodies in pemphigus reside in the amino-terminal adhesive region of desmogleins which are unmasked by proteolytic processing of prosequence. (2009)
  • Author(s): Yokouchi M, Saleh MA, Kuroda K, Hachiya T, Stanley JR, Amagai M, Ishii K
  • Journal Title: J Invest Dermatol. 129 Pages: 2156-2166
  • Peer Reviewed
• [Journal Article] Pathogenic anti-desmoglein monoclonal antibodies demonstrate variable ELISA activity due to preferential binding of mature versus proprotein isoforms of desmoglein 3 (2009)
  • Author(s): Sharma P, Choi EJ, Kuroda K, Hachiya T, Ishii K, Payne AS
  • Journal Title: J Invest Dermatol. 129 Pages: 2309-2312
  • Peer Reviewed
• [Journal Article] Antibodies to the desmoglein 1 precursor proprotein but not to the mature cell surface protein cloned from individuals without pemphigus. (2009)
  • Author(s): Yamagami J, Kacir S, Ishii K, Payne AS, Siegel DL, Stanley JR
  • Journal Title: J Immunol. 183 Pages: 5615-5621
  • Peer Reviewed
• [Journal Article] Isolation of Pathogenic Monoclonal Anti-Desmoglein 1 Human Antibodies by Phage Display of Pemphigus Foliaceus Autoantibodies (2008)
  • Author(s): Ishii K, Lin C, Siegel DL, Stanley JR
  • Journal Title: J Invest Dermatol. 128(4) Pages: 939-948
  • Peer Reviewed
• [Presentation] 天疱瘡におけるELISA法による血清診断とPDAIによる重症度判定 シンポジウム3「自己免疫水疱症の診断・治療2010 (2010)
  • Author(s): 石井健
  • Organizer: 第62回日本皮膚科学会西部支部学術大会
  • Place of Presentation: 倉敷
  • Year and Date: 2010-10-24
• [Presentation] 天疱瘡におけるELISA法による血清診断とPDAIによる重症度判定 (2010)
  • Author(s): 石井健
  • Organizer: 第62回日本皮膚科学会西部支部学術大会
  • Place of Presentation: 倉敷
• [Presentation] Characterization of monoclonal Desmoglein 3 autoantibodies isolated from a paraneoplastic pemphigus patient by phage display (2010)
  • Author(s): Saleh M
  • Organizer: 35th Annunal meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: 和歌山
• [Presentation] The majority of anti-desmoglein autoantibodies in pemphigus target epitopes which are unmasked by proteolytic processing of prosequence. (2009)
  • Author(s): Ishii K, Yokouchi M, Saleh MA, Amagai M
  • Organizer: The 4^<th> joint meeting of Japanese dermatology association and Australasian college of Dermatologists
  • Place of Presentation: 札幌
  • Year and Date: 2009-07-11
• [Presentation] Pathogenic pemphigus autoantibodies target the amino-terminal adhesive sites of desmogleins which are unmasked by proteolytic processing of prosequence. (2009)
  • Author(s): Ishii K
  • Organizer: International Pemphigus Meeting
  • Place of Presentation: スイス
  • Year and Date: 2009-06-29
• [Presentation] The majority of anti-desmoglein autoantibodies in pemphigus target epitopes which are unmasked by proteolytic processing of prosequence (2009)
  • Author(s): Ishii K, Yokouchi M, Saleh MA, Amagai M
  • Organizer: The 4^<th> joint meeting of Japanese dermatology association and Australasian college of Dermatologists
  • Place of Presentation: Sapporo, Japan
• [Presentation] Pathogenic pemphigus autoantibodies target the amino-terminal adhesive sites of desmogleins which are unmasked by proteolytic processing of prosequence (2009)
  • Author(s): 石井健
  • Organizer: International Pemphigus Meeting, Berne
  • Place of Presentation: Switzerland
• [Presentation] デスモグレイン(Dsg)ELISA法の改良を目指した天庖瘡自己抗体の病的エピトープの解析 (2008)
  • Author(s): 石井健
  • Organizer: 第822回日本皮膚科学会東京支部研究地方会
  • Place of Presentation: 東京
  • Year and Date: 2008-12-20
• [Presentation] デスモグレイン(Dsg)ELISA法の改良を目指した天疱瘡自己抗体の病的エピトープの解析 (2008)
  • Author(s): 石井健、横内麻里子、Marwah Adly、黒田慶子、蜂矢隆久、天谷雅行
  • Organizer: 第822回日本皮膚科学会東京支部研究地方会
  • Place of Presentation: 東京
• [Presentation] Two pathogenic anti-desmoglein 1 (Dsg1) monoclonal antibodies isolated from one pemphigus foliaceus (PF) patient define major Dsg1 epitopes recognized by most pemphigus patients (2008)
  • Author(s): Ishii K, Adly M, Yokouchi M, Stanley JR, Amagai M
  • Organizer: International Investigative Dermatology 2008
  • Place of Presentation: Kyoto, Japan
• [Presentation] Proteolytic processing of precursor desmoglein 1 (Dsg1) unmasks pathogenic epitopes (2008)
  • Author(s): Yokouchi M, Ishii K, Stanley JR, Amagai M
  • Organizer: Post IID 2008 satellite international meeting on autoimmune bullous diseases
  • Place of Presentation: Otsu, Japan
• [Presentation] Two pathogenic anti-desmoglein 1 (Dsg1)monoclonal antibodies isolated from one pemphigus foliaceus (PF)patient define major Dsgl epitopes recognized by most pemphigus patients. (2008)
  • Author(s): Ishii K
  • Organizer: International Investigative Dermatology 2008
  • Place of Presentation: 京都
• [Presentation] Proteolytic processing of precursor desmoglein 1 (Dsgl)unmasks pathogenic epitopes (2008)
  • Author(s): Yokouchi M
  • Organizer: Post IID 2008 satellite international meeting on autoimmune bullous diseases
  • Place of Presentation: 大津
• [Presentation] カドヘリンスーパーフアミリーの多様性デスモゾーマルカドヘリン天庖瘡自己抗体解析からの教訓 (2008)
  • Author(s): 石井健
  • Organizer: 第60回日本細胞生物学会大会
  • Place of Presentation: 横浜
• [Presentation] 病的エピトープに着目したデスモグレインELISAの改良 (2008)
  • Author(s): 横内麻里子
  • Organizer: 第30回水庖症研究会
  • Place of Presentation: 東京