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Identification of IgG monoclonal antibodies associated with the pathogenesis of bullous pemphigoid and development of a new therapy targeting the antibodies.

Research Project

Project/Area Number 23591639
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionUniversity of Toyama

Principal Investigator

SHIMIZU Tadamichi  富山大学, 大学院医学薬学研究部(医学), 教授 (70260396)

Co-Investigator(Kenkyū-buntansha) KISHI Hiroyuki  富山大学, 大学院医学薬学研究部(医学), 准教授 (60186210)
MAKINO Teruhiko  富山大学, 大学院医学薬学研究部(医学), 准教授 (90359711)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords水疱性類天疱瘡 / モノクローナル抗体 / タイプ17コラーゲン / ISAAC法 / BP180 / TypeXVIIコラーゲン / ISSAC / サイトカイン / ケモカイン / MIF / 自己抗体
Research Abstract

Bullous pemphigoid (BP) is an autoimmune blistering disease caused by IgG autoantibodies against the NC16a domain of BP180. In this study, we attempted to isolate IgG monoclonal antibodies against NC16a and identify epitopes strongly associated with the pathogenesis of BP. Antigen-specific antibody-secreting cells (ASCs) were collected from the patient's peripheral blood monocytes using an Immunospot array assay on a chip (ISAAC). IgG variable region cDNA was amplified from each ASC and ligated to an expression vector. Monoclonal antibodies were obtained from the culture supernatant of HEK293T cells transfected with the expression vectors. These monoclonal antibodies specifically recognized 542-566 amino acids of BP180. We perform to examine whether the antibodies induce blister formation in the human skin and to obtain other types of monoclonal antibodies from BP patients. In addition, we plan to develop a new therapy targeting disease-related antibodies.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (54 results)

All 2014 2013 2012 2011 Other

All Journal Article (21 results) (of which Peer Reviewed: 20 results) Presentation (16 results) (of which Invited: 1 results) Book (16 results) Remarks (1 results)

  • [Journal Article] Induction of skin lesions by ultraviolet B irradiation in a case of pemphigus erythematosus2014

    • Author(s)
      Makino T, Seki Y, Hara H, Mizawa M, Matsui K, Shimizu K, Shimizu T
    • Journal Title

      Acta Derma Venereol

      Volume: (in press) Issue: 4 Pages: 487-488

    • DOI

      10.2340/00015555-1781

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bullous pemphigoid with IgG anti-LAD-1 antibodies2014

    • Author(s)
      Matsui K, Makino T, Takegami Y, Murayama S, Seki Y, Ishii N, Hashimoto T, Shimizu T
    • Journal Title

      Eur J Dermatol

      Volume: 24 Issue: 2 Pages: 275-276

    • DOI

      10.1684/ejd.2014.2322

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of MIF in Basement Membrane Damage in Chronically UVB- Exposed Skin in Mice2014

    • Author(s)
      Yoshihisa Y, Norisugi O, Matsunaga K, Nishihira J, Shimizu T
    • Journal Title

      PLoS One

      Volume: 9 Issue: 2 Pages: e89569-e89569

    • DOI

      10.1371/journal.pone.0089569

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] In vitro cytokine expression by PBMCs in herbal drug-induced skin eruption2014

    • Author(s)
      Norisugi O, Yoshihisa Y, Shimizu K, Shimizu T
    • Journal Title

      Acta Derma Venereol

      Volume: 94 Issue: 1 Pages: 58-62

    • DOI

      10.2340/00015555-1631

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Coexistence of antilaminin-332-type mucous membrane pemphigoid, lamina lucida-type linear IgA bullous dermatosis and Sjogren syndrome.2013

    • Author(s)
      Takegami Y, Makino T, Matsui K, Ueda C, Fukuda S, Hashimoto T, Shimizu T
    • Journal Title

      Clin Exp Dermatol.

      Volume: 38 Issue: 2 Pages: 194-196

    • DOI

      10.1111/ced.12030

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and histopathological features of itch in alopecia areata patients.2013

    • Author(s)
      Yamakoshi T, Andoh T, Makino T, Kuraishi Y, Shimizu T.
    • Journal Title

      Acta Derm-Venereol.

      Volume: 93 (5) Issue: 5 Pages: 575-576

    • DOI

      10.2340/00015555-1613

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Trichohyalin-like 1 protein, a member of fused S100 proteins, is expressed in normal and pathologic human skin.2013

    • Author(s)
      Yamakoshi T, Makino T, Rheman UM, Yoshihisa Y, Sugimori M, Shimizu T.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 432 (1) Issue: 1 Pages: 66-72

    • DOI

      10.1016/j.bbrc.2013.01.084

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stress evaluation in adult patients with atopic dermatitis using salivary cortisol.2013

    • Author(s)
      Mizawa M, Yamaguchi M, Ueda C, Makino T, Shimizu T.
    • Journal Title

      Bio Med Res Int.

      Volume: 2013; 138027. Pages: 138027-138027

    • DOI

      10.1155/2013/138027

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Repigmentation from epidermis around acrosyringium in piebald skin: an ultrastructural examination.2013

    • Author(s)
      Makino T, Yanagihara M, Oiso N, Mizawa M, Shimizu T.
    • Journal Title

      Br J Dermatol.

      Volume: 168 (4) Issue: 4 Pages: 910-912

    • DOI

      10.1111/bjd.12116

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Granulomatosis with polyangiitis of the skin induced by a chest drainage tube.2013

    • Author(s)
      Ueda C, Makino T, Mizawa M, Norisugi O, Shimizu T.
    • Journal Title

      Eur J Dermatol.

      Volume: 23 Issue: 4 Pages: 565-567

    • DOI

      10.1684/ejd.2013.2094

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 紫外線誘導表皮基底膜コラーゲン分解・変性に及ぼすMIFの影響2013

    • Author(s)
      清水忠道
    • Journal Title

      加齢皮膚医学セミナー

      Volume: 8 Pages: 29-32

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel mutation of the KRT 10 gene in a Japanese patient with epidermolytic ichthyosis2012

    • Author(s)
      Makino T., Furuichi M., Asano Y., Shimizu T.
    • Journal Title

      J. Dermatol

      Volume: 39 Issue: 1 Pages: 87-89

    • DOI

      10.1111/j.1346-8138.2011.01234.x

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Alkannin, HSP70 inducer, protects against UVB-induced apoptosis in human keratinocytes.2012

    • Author(s)
      Yoshihisa Y., Hassan M.A., Furusawa Y., Tabuchi Y., Kondo T., and Shimizu T
    • Journal Title

      PLoS One.

      Volume: 7(10) Issue: 10 Pages: e47903-e47903

    • DOI

      10.1371/journal.pone.0047903

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The anti-inflammatory effects of platinum nanoparticles on the LPS-induced inflammatory response in macrophages.2012

    • Author(s)
      Rehman U.M., Yoshihisa Y., Miyamoto Y., and Shimizu T.
    • Journal Title

      Inflamm .Res.

      Volume: 61 Issue: 11 Pages: 1177-1185

    • DOI

      10.1007/s00011-012-0512-0

    • Related Report
      2012 Research-status Report
  • [Journal Article] Effects of platinum nanoparticles on heat- and UV-induced apoptosis.2011

    • Author(s)
      Yoshihisa Y., Shimizu T. et al.
    • Journal Title

      Exp dermatol.

      Volume: 1 Issue: 11 Pages: 162-165

    • DOI

      10.1111/j.1600-0625.2010.01128.x

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Macrophage migration inhibitory factor is essential for eosinophil recruitment in allergen-induced skin inflammation2011

    • Author(s)
      Yoshihisa Y., Makino T., et. al
    • Journal Title

      J.Invest.Dermatol.

      Volume: 131 Issue: 4 Pages: 925-931

    • DOI

      10.1038/jid.2010.418

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] SOD/catalase mimetic platinum nanoparticles inhibit heat-induced apoptosis in human lymphoma U937 and HH cells.2011

    • Author(s)
      Yoshihisa Y., Shimizu T. et al.
    • Journal Title

      Free Radic Res.

      Volume: 45 Pages: 326-335

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fibrous mass in the chin due to a unique cause.2011

    • Author(s)
      Asano Y., Makino T., Shimizu T. et al
    • Journal Title

      Arch. Dermatol.

      Volume: 147 Issue: 7 Pages: 868-869

    • DOI

      10.1001/archdermatol.2011.177

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] UV-B Radiation Induces Macrophage Migration Inhibitory Factor-Mediated Melanogenesis through Activation of Protease-Activated Receptor-2 and Stem Cell Factor in Keratinocytes.2011

    • Author(s)
      Enomoto A., Shimizu T. et al
    • Journal Title

      Am. J. Pathol.

      Volume: 178 Issue: 2 Pages: 679-687

    • DOI

      10.1016/j.ajpath.2010.10.021

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Detection of antibodies to epidermal transglutaminase but not tissue transglutaminase in Japanese patients with dermatitis herpetiformis2011

    • Author(s)
      Asano Y., Makino T., et. al
    • Journal Title

      Br.J.Dermatol.

      Volume: 164 Issue: 4 Pages: 883-884

    • DOI

      10.1111/j.1365-2133.2010.10153.x

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Unusual bullous pemphigoid without infiltration of inflammatory cells in the skin lesions

    • Author(s)
      Hara H, Makino T, Matsui K, Takegami Y, Koga H, Fukuda S, Ishii N, Hashimoto T, Shimizu T
    • Journal Title

      Eur J Dermatol

      Volume: (in press)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] アトピー性皮膚炎と眼疾患―炎症性サイトカインMIFとの関連―2013

    • Author(s)
      清水忠道
    • Organizer
      第2回眼と全身疾患セミナーin札幌
    • Place of Presentation
      札幌(特別講演)
    • Year and Date
      2013-12-18
    • Related Report
      2013 Final Research Report
  • [Presentation] 好中球優位の細胞浸潤を認めた水疱性類天疱瘡の2例2013

    • Author(s)
      原寛,牧野輝彦,松井恒太郎,竹上與志昌,古賀浩嗣,福田俊平,石井文人,橋本隆,清水忠道
    • Organizer
      第438回日本皮膚科学会北陸地方会
    • Place of Presentation
      金沢
    • Year and Date
      2013-06-23
    • Related Report
      2013 Final Research Report
  • [Presentation] Successful treatment of lichen amyloidisis using CO2 surgical laser2013

    • Author(s)
      Shimizu T, Yamakoshi T, Norisugi O
    • Organizer
      World Laserology Congress, Joint Congress of The 5th International Phototherapy Association (IPTA), International Society for Laser Surgery and Medicine (ISLSM), World Federation of Societies for Laser Medicine and Surgery (WFSLMS)
    • Place of Presentation
      Vilnius, Lithuania
    • Related Report
      2013 Final Research Report
  • [Presentation] Coexistence of antilaminin-332-type mucous membrane pemphigoid, lamina lucida-type linear IgA bullous dermatosis and Sjögren syndrome2013

    • Author(s)
      Takegami Y, Makino T, Matsui K, Ueda C, Fukuda S, Hashimoto T, Shimizu T
    • Organizer
      Clin Exp Dermatol
    • Place of Presentation
      (38 (2) : 194-6)
    • Related Report
      2013 Final Research Report
  • [Presentation] 紫外線曝露により増悪した紅斑性天疱瘡の2例2013

    • Author(s)
      関友里,牧野輝彦,原寛,竹上與志昌,松井恒太郎,清水忠道
    • Organizer
      第64回日本皮膚科学会中部支部学術大会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] In vitro cytokine expression by PBMCs in the diagnosis of herbal drug-induced skin eruption.2013

    • Author(s)
      Norisugi O, Yoshihisa Y, Shimizu K, Shimizu T.
    • Organizer
      The 6th International Investigative Dermatology Meeting in 2013
    • Place of Presentation
      Edinburgh, Scotland.
    • Related Report
      2013 Annual Research Report
  • [Presentation] Astaxanthin, a xanthophyll carotenoid, inhibits ultraviolet-induced apoptosis in keratinocytes.2013

    • Author(s)
      Yoshihisa Y, Shimizu T.
    • Organizer
      The 6th International Investigative Dermatology Meeting in 2013
    • Place of Presentation
      Edinburgh, Scotland.
    • Related Report
      2013 Annual Research Report
  • [Presentation] MIF in the stratum corneum as a biomarker of skin irritation.2013

    • Author(s)
      Yasuda C, Enomoto A, Takahashi M, Tohgaki T, Ishiwatari S, Yoshihisa Y, Shimizu T, Matsukuma S.
    • Organizer
      The 6th International Investigative Dermatology Meeting in 2013
    • Place of Presentation
      Edinburgh, Scotland.
    • Related Report
      2013 Annual Research Report
  • [Presentation] Successful treatment of lichen amyloidisis using CO2 surgical laser.2013

    • Author(s)
      Shimizu T, Yamakoshi T, Norisugi O.
    • Organizer
      World Laserology Congress, Joint Congress of The 5th International Phototherapy Association (IPTA), (ISLSM), World Federation of Societies for Laser Medicine and Surgery (WFSLMS)
    • Place of Presentation
      Vilnius, Lithuania.
    • Related Report
      2013 Annual Research Report
  • [Presentation] Combined effects of CO2 surgical laser ablation and photodynamic therapy in the treatment of multiple Bowen’s disease.2013

    • Author(s)
      Mizawa M, Shimizu K, Shimizu T.
    • Organizer
      World Laserology Congress, Joint Congress of The 5th International Phototherapy Association (IPTA), (ISLSM), World Federation of Societies for Laser Medicine and Surgery (WFSLMS)
    • Place of Presentation
      Vilnius, Lithuania.
    • Related Report
      2013 Annual Research Report
  • [Presentation] 皮膚科医にとっての漢方薬とエビデンス2013

    • Author(s)
      清水忠道
    • Organizer
      第112回日本皮膚科学会総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] An analysis of profilaggrin N-terminal fragment function in keratinocyte terminal differentiation2012

    • Author(s)
      Makino T., Yamamoto M., Yamakoshi T., Rahaman MR., Hibino T., and Shimizu T.
    • Organizer
      The 72nd Annual Meeting the Society for Investigative Dermatology
    • Place of Presentation
      Raleigh, North Carolina USA
    • Related Report
      2013 Final Research Report
  • [Presentation] An analysis of profilaggrin N-terminal fragment function in keratinocyte terminal differentiation.2012

    • Author(s)
      Makino T., Yamamoto M., Yamakoshi T., Rahaman MR., Hibino T., and Shimizu T.
    • Organizer
      The 72nd Annual Meeting the Society for Investigative Dermatology
    • Place of Presentation
      Raleigh, North Carolina USA.
    • Related Report
      2012 Research-status Report
  • [Presentation] 抗ラミニンα3抗体と抗LAD-1抗体を検出した粘膜類天疱瘡の1例2011

    • Author(s)
      竹上與志昌,牧野輝彦,上田智恵子,松井恒太郎,清水忠道,福田俊平,橋本隆
    • Organizer
      第432回日本皮膚科学会北陸地方会
    • Place of Presentation
      福井
    • Year and Date
      2011-12-11
    • Related Report
      2013 Final Research Report
  • [Presentation] MIF and ultraviolet radiation-induced skin damage2011

    • Author(s)
      Shimizu T
    • Organizer
      International MIF Symposium 2011(招待講演)
    • Place of Presentation
      New Haven, USA
    • Related Report
      2011 Research-status Report
  • [Presentation] MIFのUVB誘導メラニン形成に及ぼす影響2011

    • Author(s)
      吉久陽子,清水忠道ほか
    • Organizer
      第33回日本光医学・光生物学会学術大会
    • Place of Presentation
      大阪
    • Related Report
      2011 Research-status Report
  • [Book] Cellular Response to Physical and Chemical Stress and Therapeutic Applications2013

    • Author(s)
      Shimizu T, Kondo T. Editors
    • Publisher
      New York : Nova Science Publishers, Inc
    • Related Report
      2013 Final Research Report
  • [Book] HSP70 inducers protect against ultraviolet-induced apoptosis in keratinocytes."Cellular Response to Physical and Chemical Stress and Therapeutic Applications"2013

    • Author(s)
      Yoshihisa Y, Shimizu T(edited by Tadamichi Shimizu and Takashi Kondo)
    • Publisher
      Nova Science Publishers, Inc, New York
    • Related Report
      2013 Final Research Report
  • [Book] Platinum : Compounds Production and Applications, Chaptor 5, Platinum nanoparticle and inflammation2013

    • Author(s)
      Yoshihisa Y, Shimizu T(edited by Varennikov L, Yedemsky E)
    • Publisher
      Nova Science Publishers, Inc, New York
    • Related Report
      2013 Final Research Report
  • [Book] Editors. Cellular Response to Physical and Chemical Stress and Therapeutic Applications.2013

    • Author(s)
      Shimizu T, Kondo T.
    • Total Pages
      204
    • Publisher
      New York : Nova Science Publishers, Inc
    • Related Report
      2013 Annual Research Report
  • [Book] Cellular Response to Physical and Chemical Stress and Therapeutic Applications.2013

    • Author(s)
      Yoshihisa Y, Shimizu T.
    • Total Pages
      16
    • Publisher
      Nova Science Publishers, Inc. New York
    • Related Report
      2013 Annual Research Report
  • [Book] Platinum: Compounds Production and Applications.2013

    • Author(s)
      Yoshihisa Y, Shimizu T.
    • Total Pages
      7
    • Publisher
      Nova Science Publishers, Inc, New York
    • Related Report
      2013 Annual Research Report
  • [Book] 1冊でわかる最新皮膚科治療(皮膚科サブスペシャリティーシリーズ)2013

    • Author(s)
      清水忠道
    • Total Pages
      3
    • Publisher
      文光堂
    • Related Report
      2013 Annual Research Report
  • [Book] 皮膚の測定・評価法バイブル2013

    • Author(s)
      山口昌樹,清水忠道
    • Total Pages
      9
    • Publisher
      技術情報教会
    • Related Report
      2013 Annual Research Report
  • [Book] Monthly Book Derma No. 211.2013

    • Author(s)
      三澤 恵,清水忠道
    • Total Pages
      4
    • Publisher
      全日本病院出版会
    • Related Report
      2013 Annual Research Report
  • [Book] Chapter 8 “Matrix Metalloproteinases: Biology, Functions and Clinical Implications”2012

    • Author(s)
      Shimizu T.
    • Total Pages
      3
    • Publisher
      Nova Science Publishers
    • Related Report
      2012 Research-status Report
  • [Book] Monthly Book Derma No. 1912012

    • Author(s)
      清水忠道
    • Total Pages
      6
    • Publisher
      全日本病院出版会
    • Related Report
      2012 Research-status Report
  • [Book] Macrophage migration inhibitory factor overexpression accelerates photocarcinogenesis in the skin,"Skin Cancers- Risk Factors, Prevention and Therapy"2011

    • Author(s)
      Shimizu T(edited by Caterina AM La Porta)
    • Publisher
      InTech Publisher, Rijeka
    • Related Report
      2013 Final Research Report
  • [Book] Skin Cancers- Risk Factors, Prevention and Therapy2011

    • Author(s)
      Shimizu T
    • Total Pages
      13
    • Publisher
      InTech Publisher
    • Related Report
      2011 Research-status Report
  • [Book] 皮膚疾患 最新の治療2011-20122011

    • Author(s)
      清水忠道
    • Total Pages
      1
    • Publisher
      南江堂
    • Related Report
      2011 Research-status Report
  • [Book] 薬疹診療のフロントライン2011

    • Author(s)
      清水忠道
    • Total Pages
      3
    • Publisher
      中山書店
    • Related Report
      2011 Research-status Report
  • [Book] ガイドライン外来診療20112011

    • Author(s)
      清水忠道
    • Total Pages
      4
    • Publisher
      医学書院
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://www.med.u-toyama.ac.jp/derma2/index.html

    • Related Report
      2013 Final Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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