Functional analyses of 230-kDa bullous pemphigoid antigen 1 as cell adhesion molecules and immunogenic epitopes

• Project/Area Number: 18K08286
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Hirosaki University
• Principal Investigator: Aizu Takayuki 弘前大学, 医学研究科, 客員研究員 (00400135)
• Co-Investigator(Kenkyū-buntansha): 松崎 康司 弘前大学, 医学部附属病院, 講師 (50322946)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 水疱性類天疱瘡 / BP230 / 自己抗体 / 表皮水疱症 / BP230－KOマウス / 細胞接着タンパク / BP230-KOマウス / ヘミデスモゾーム

Outline of Final Research Achievements

Bullous pemphigoid (BP) is an autoimmune blistering disease that targets the hemidesmosome, containing BP180 and BP230 protein. Whereas the role of anti-BP180 antibodies has been characterized, the pathogenicity of anti-BP230 antibodies remains unclear. In this study, we analyzed the effect of BP230 protein on wound-healing using BP230-knockout mice. Furthermore, we confirmed that anti-BP230 antibodies generated subepidermal blisters in the murine skin.

Academic Significance and Societal Importance of the Research Achievements

BP230を標的とした表皮水疱症の疾患モデルマウスは存在せず、皮膚ヘミデスモゾームにおけるBP230の役割を明らかにすることができ、また水疱性類天疱瘡の発症機序とその病態を解明することができた。既存の治療に難渋するBP患者への新規治療法確立への道標となりうる。

Research Products

• [Journal Article] Microbiological analysis of 1000‐Yen banknotes in a hospital environment (2021)
  • Author(s): Minakawa S, Terui H, Matsuzaki Y, Kimura M, Saito N, Kayaba H Sawamura D.,Microbiological analysis of 1000-Yen banknotes in a hospital environment. J Cutan Immunol Allergy. 2020;3(4)
  • Journal Title: Journal of Cutaneous Immunology and Allergy Volume: 4 Issue: 1 Pages: 19-21
  • DOI: 10.1002/cia2.12144
  • Peer Reviewed
• [Journal Article] Autoantibodies to BPAG1e Trigger Experimental Bullous Pemphigoid in Mice. (2021)
  • Author(s): Makita Eiko, Matsuzaki Yasushi, Fukui Tomohisa, Matsui Akinobu, Minakawa Satoko, Nakano Hajime, Ito Koichi Kijima Hiroshi, Sawamura Daisuke
  • Journal Title: The Journal of Investigative Dermatology Volume: 4 Issue: 5 Pages: 1167-1176
  • DOI: 10.1016/j.jid.2020.08.031
  • Peer Reviewed / Open Access
• [Journal Article] Partial spontaneous regression of pediatric large fibroblastic connective tissue nevus (2020)
  • Author(s): Takahashi Mika、Matsuzaki Yasushi、Nakano Hajime、Sawamura Daisuke
  • Journal Title: The Journal of Dermatology Volume: 1 Issue: 6 Pages: 12-12
  • DOI: 10.1111/1346-8138.15320
  • Peer Reviewed / Open Access
• [Journal Article] Current status of Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus isolated from patients with skin and soft tissue infections in Japan (2020)
  • Author(s): Nakaminami Hidemasa、Ozawa Kazuya、Sasai Nao、Ikeda Masami、Nemoto Osamu、Baba Naoko、Matsuzaki Yasushi、Sawamura Daisuke、Shimoe Fumiko、Inaba Yoichi、Kobayashi Yoko、Kawasaki Satoru、Ueki Toru、Funatsu Sakae、Shirahama Shigeho、Noguchi Norihisa
  • Journal Title: The Journal of Dermatology Volume: 47 Issue: 11 Pages: 1280-1286
  • DOI: 10.1111/1346-8138.15506
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of the mechanism underlying a mild phenotype of hereditary coproporphyria due to a homozygous missense mutation in the transcription initiation codon of the coproporphyrinogen III oxidase gene (2020)
  • Author(s): Fukui Tomohisa、Akasaka Eijiro、Rokunohe Daiki、Matsuzaki Yasushi、Sawamura Daisuke、Kabashima Kenji、Nakano Hajime
  • Journal Title: Journal of Dermatological Science Volume: 100 Issue: 2 Pages: 156-159
  • DOI: 10.1016/j.jdermsci.2020.06.006
  • Peer Reviewed
• [Journal Article] Mutations in FLG, the gene‐coding profilaggrin/filaggrin, are associated with putative hay fever in patients with atopic dermatitis. (2020)
  • Author(s): Minakawa S, Matsuzaki Y, Suwa H. Kono M, Akiyama M, Sawamura D.
  • Journal Title: Journal of Cutaneous Immunology and Allergy Volume: 3 Issue: 4 Pages: 98-100
  • DOI: 10.1002/cia2.12125
  • Peer Reviewed
• [Journal Article] Decreased cardiac pacemaking and attenuated beta-adrenergic response in TRIC-A knockout mice. (2020)
  • Author(s): Murakami M, Toyama Y, Yonekura M, Ohba T, Matsuzaki Y, Sawamura D, Murakami AM, Nishi M, Itagaki S, Tomita H, Takeshima H.
  • Journal Title: Plos ONE Volume: 15 Issue: 12 Pages: 1-12
  • DOI: 10.1371/journal.pone.0244254
  • Peer Reviewed / Open Access
• [Journal Article] Dipeptidyl peptidase‐4 inhibitor‐associated anti‐laminin‐γ1 (p200) pemphigoid in a patient with psoriasis vulgaris (2019)
  • Author(s): Minakawa Satoko、Matsuzaki Yasushi、Hashimoto Takashi、Ishii Norito、Nishie Wataru、Kayaba Hiroyuki、Sawamura Daisuke
  • Journal Title: The Journal of Dermatology Volume: 47 Issue: 1
  • DOI: 10.1111/1346-8138.15126
  • Peer Reviewed / Open Access
• [Journal Article] Pediculus humanus capitis: Pyrethroid resistance and utility of scanning electron microscopy (2019)
  • Author(s): Minakawa Satoko、Matsuzaki Yasushi、Yamaguchi Sayaka、Takahashi Kenzo、Kayaba Hiroyuki、Sawamura Daisuke
  • Journal Title: The Journal of Dermatology Volume: 46 Issue: 11
  • DOI: 10.1111/1346-8138.15009
  • Peer Reviewed / Open Access
• [Journal Article] Two cases of ichthyosis and their EPR analyses of stratum corneum (2019)
  • Author(s): S. Minakawa, Y. Mastuzaki, K. Nakagawa, T. Kaneko, E. Akasaka, D. Sawamura
  • Journal Title: Journal of Cutaneous Immunology and Allergy Volume: - Issue: 3 Pages: 1-3
  • DOI: 10.1002/cia2.12057
  • Peer Reviewed / Open Access
• [Presentation] ニボルマブ＋イピリムマブ併用療法により小腸炎を生じた肛門部悪性黒色腫 (2019)
  • Author(s): 会津隆幸、滝吉典子、原 憲司、是川あゆ美、金子高英、 中野 創、澤村大輔、櫻庭裕丈
  • Organizer: 第35回日本皮膚悪 性腫瘍学会学術大会
• [Presentation] 爪下有棘細胞癌 (2019)
  • Author(s): 中島康爾、澤村大輔、福井智久、相樂千尋、会津隆幸、中野 創
  • Organizer: 第35回日本 皮膚悪性腫瘍学会学術大会
• [Presentation] Dabrafenib+Trametinib併用療法によって生じた発熱性好中球減少症 (2019)
  • Author(s): 金子高英、福井智久、相樂千尋、滝吉典子、六戸大樹、会津隆幸、澤村大輔、須賀 康
  • Organizer: 第35回日本 皮膚悪性腫瘍学会学術大会
• [Presentation] ニボルマブ＋イピリムマブ併用療法中に唾液量の低下をきたした悪性黒色腫 (2019)
  • Author(s): 会津 隆幸、是川あゆ美、原 憲司、滝吉典子、金子高英、中野 創、澤村大輔、高畑淳子
  • Organizer: 第118回日本皮膚科学会総会
• [Presentation] 白色海綿状母斑の1例 (2019)
  • Author(s): 相樂千尋、会津隆幸、中野 創、澤村大輔
  • Organizer: 日本皮膚科学会東北六県合同学術大会第386回例会
• [Presentation] 白色海綿状母斑の1例 (2019)
  • Author(s): 相樂千尋、会津隆幸、中野 創、澤村大輔
  • Organizer: 第34回角化症研究会
• [Presentation] ランダム皮膚生検が診断に有用であったintravascular large B-cell lymphoma (2019)
  • Author(s): 吉川未雪、相樂千尋、福士花恋、会津隆幸、中野 創、澤村大輔、山形和史
  • Organizer: 日本皮膚科学会青森地方会第387回例会