Analysis of mechanisms for blister formation via autoantibodies-mediated interference of adhesion system of laminins and integrins

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659534
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Dermatology
• Research Institution: Kurume University
• Principal Investigator: HASHIMOTO Takashi 久留米大学, 医学部, 教授 (20129597)
• Co-Investigator(Kenkyū-buntansha): HAMADA Takahiro 久留米大学, 医学部, 講師 (40320204) ; ISHII Norito 久留米大学, 医学部, 講師 (80330827) ; TSUCHISAKA Atsunari 久留米大学, 医学部, 研究員 (50599313) ; TEYE Kwesi 久留米大学, 医学部, 研究員 (30599303)
• Project Period (FY): 2012-04-01 – 2013-03-31
• Keywords: 眼型粘膜類天疱瘡 / インテグリンベータ4 / ヘミデスモソーム

Research Abstract

By novel immunoblotting using newly established hemidesmosome-rich fraction, in which BP230, BP180, laminin 332, integrin alpha 6, integrin beta 4 are concentrated, IgG antibodies in the sera from patients with pure ocular mucous membrane pemphigoid (MMP) reacted specifically with integrin beta 4, as well as recombinant protein of integrin beta 4. IgG antibodies in the sera from patients with anti-laminin 332 MMP reacted with 3 laminin 332 subunits in various patterns. These results indicated that major autoantigen for pure ocular MMP is integrin beta 4. In addition, the novel immunoblotting using newly established hemidesmosome-rich fraction should be a useful tool to detect various autoantigen present at epidermal basement membrane zone, including integrin beta 4 and laminin 332.

Research Products

• [Journal Article] Zillikens D : From epidemiology and genetics to diagnostics, outcome measures and novel treatments in autoimmune bullous diseases (2014)
  • Author(s): Ludwig RJ, Borradori L, Diaz LA, Hashimoto T, Hertl M, Ibrahim SM, Jonkman MF, Kitajima Y, Murrell DF, Schmidt E, Shimizu H, Stanley JR, Woodley D
  • Journal Title: J Invest Dermatol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Immunological and Statistical Studies of Anti-BP180 Antibodies in Paraneoplastic Pemphigus (2014)
  • Author(s): Tsuchisaka A, Kawano H, Yasukochi A, Teye K, Ishii N, Koga H, Sogame R, Ohzono A, Krol RP, Kawakami T, Furumura M, Ohata C, Li X, Hashimoto T
  • Journal Title: J Invest Dermatol
  • DOI: 10.1038/jid.2014.151
  • Peer Reviewed
• [Journal Article] Ex Vivo Pathogenicity of Anti-Laminin gamma1 Autoantibodies (2014)
  • Author(s): Florea F, Bernards C, Caproni M, Kleindienst J, Hashimoto T, Koch M, Sitaru C
  • Journal Title: Am J Pathol Volume: 184(2) Pages: 494-506
  • DOI: 10.1016/j.ajpath.2013.10.019
  • Peer Reviewed
• [Journal Article] Molecular diagnosis of autoimmune blistering diseases (2013)
  • Author(s): Tsuruta D, Dainichi T, Hamada T, Ishii N, Hashimoto T
  • Journal Title: Methods Mol Biol Volume: 961 Pages: 17-32
  • DOI: 10.1007/978-1-62703-227-8_2
  • Peer Reviewed
• [Journal Article] Three Cases of Linear IgA/IgG Bullous Dermatosis Showing IgA and IgG Reactivity With Multiple Antigens, Particularly Laminin-332 (2013)
  • Author(s): Sakaguchi M, Bito T, Oda Y, Kikusawa A, Nishigori C, Munetsugu T, Yokozeki H, Itotani Y, Niguma T, Tsuruta D, Tateishi C, Ishii N, Koga H, Hashimoto T
  • Journal Title: JAMA Dermatol Volume: 149(11) Pages: 1308-1313
  • DOI: 10.1001/jamadermatol.2013.5691
  • Peer Reviewed
• [Journal Article] An attempt to develop mouse model for anti-laminin gamma1 pemphigoid (2013)
  • Author(s): Koga H, Ishii N, Dainichi T, Tsuruta D, Hamada T, Ohata C, Karashima T, Furumura M, Hashimoto T
  • Journal Title: J Dermatol Sci Volume: 70(2) Pages: 108-115
  • DOI: 10.1016/j.jdermsci.2013.01.001
  • Peer Reviewed
• [Journal Article] Bullous pemphigoid IgG induces BP180 internalization via a macropinocytic pathway (2013)
  • Author(s): Hiroyasu S, Ozawa T, Kobayashi H, Ishii M, Aoyama Y, Kitajima Y, Hashimoto T, Jones JC, Tsuruta D
  • Journal Title: Am J Pathol Volume: 182(3) Pages: 828-840
  • DOI: 10.1016/j.ajpath.2012.11.029
  • Peer Reviewed
• [Journal Article] Pathogenicity of autoantibodies in anti-p200 pemphigoid (2012)
  • Author(s): Vafia K, Groth S, Beckmann T, Hirose M, Dworschak J, Recke A, Ludwig RJ, Hashimoto T, Zillikens D, Schmidt E
  • Journal Title: PLoS One Volume: 7(7) Pages: e41769
  • DOI: 10.1371/journal.pone.0041769
  • Peer Reviewed
• [Journal Article] Pathogenesis of epidermolysis bullosa acquisita, an autoimmune subepidermal bullous disease (2012)
  • Author(s): Hashimoto T, Ishii N, Ohata C, Furumura M
  • Journal Title: J Pathol Volume: 228(1) Pages: 1-7
  • DOI: 10.1002/path.4062
  • Peer Reviewed
• [Journal Article] Pemphigus autoantibodies generated through somatic mutations target the desmoglein-3 cis-interface (2012)
  • Author(s): Di Zenzo G, Di Lullo G, Corti D, Calabresi V, Sinistro A, Vanzetta F, Didona B, Cianchini G, Hertl M, Eming R, Amagai M, Ohyama B, Hashimoto T, Sloostra J, Sallusto F, Zambruno G, Lanzavecchia A
  • Journal Title: J Clin Invest Volume: 122(10) Pages: 3781-3790
  • DOI: 10.1172/JCI64413
  • Peer Reviewed
• [Presentation] Identification of novel autoantigens and new classification in autoimmune bullous diseases (2013)
  • Author(s): Hashimoto T
  • Organizer: The 30-year Anniversary Symposium of Department of Dermatology, Gangnam Severance Hospital
  • Place of Presentation: Korea
  • Year and Date: 20130830-0901
• [Presentation] Identification of autoantigens and development of modern serological diagnostics for various autoimmune blistering skin diseases (poster) (2013)
  • Author(s): Hashimoto T
  • Organizer: 78^<th> Cold Spring Harbor Symposium on Quantitative Biology Immunity & Tolerance
  • Place of Presentation: NY
  • Year and Date: 20130529-0603
• [Presentation] New classification of autoimmune bullous diseases (2013)
  • Author(s): Hashimoto T, Ishii N, Tsuchisaka A, Natsuaki Y, Teye K, Numata S
  • Organizer: Takashi Hashimoto (Japan) International preIID 2013 Satellite Meeting on Autoimmune Bullous Diseases (AIBD)
  • Place of Presentation: Lubeck
  • Year and Date: 20130505-13
• [Presentation] Isolation of mouse monoclonal aitibodies reactive with maturation-related unique epitope(s) on human type VII collagen (2012)
  • Author(s): Hayakawa T, Hirako Y, Teye K, Hamada T, Ishii N, Furumura M, Tsuruta D, Tateishi C, Shinkuma S, Shimizu H, Fukano H, Shimozato K, Owaribe K, Hashimoto T
  • Organizer: The 37th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Okinawa
  • Year and Date: 20121207-09
• [Presentation] An attempt to identify antigen for IgA pemphigus accidentally showed the presence of transmembrane secretory component in keratinocytes (2012)
  • Author(s): Tsuchisaka A, Ishii N, Koga H, Hamada T, Ohata C, Furumura M, Hashimoto T
  • Organizer: The 37th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Okinawa
  • Year and Date: 20121207-09
• [Presentation] Newly developed IgA ELISAs of eukaryotic recombinant proteins of desmocollins 1-3 are more sensitive and specific than baculoprotein ELISAs (2012)
  • Author(s): Teye K, Ishii N, Koga H, Hamada T, Karashima T, Numata S, Ohata C, Furumura, M, Hashimoto T
  • Organizer: The 37th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Okinawa
  • Year and Date: 20121207-09
• [Presentation] Molecular studies of six pemphigus vulgaris cases in remission stage showed paradoxical changes of high titer antiーdesmoglein 3 antibodies (2012)
  • Author(s): Ohata C, Koga H, Ohyama B, Ishii N, Hamada T, Furumura M, Hashimoto T
  • Organizer: The 37th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Okinawa
  • Year and Date: 20121207-09