The analysis of the variable region of the patients with bullous pemphigoid autoantibody

• Project/Area Number: 20K08684
• 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: Minakawa Satoko 弘前大学, 医学部附属病院, 助教 (20436033)
• Co-Investigator(Kenkyū-buntansha): 澤村 大輔 弘前大学, 医学研究科, 教授 (60196334)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 水疱性類天疱瘡 / 自己免疫性水疱症 / BP / 抗BP180 NC16a抗体 / 抗基底膜抗体 / 自己抗体可変領域 / Bullous pemphigoid / BP180 ELISA / NC16aアフィニティーカラム / NC16aドメイン / 可変領域 / 抗BP180抗体 / NC16a / リコンビナント抗体

Outline of Research at the Start

多くのＢＰ患者で，表皮真皮境界部に存在する膜貫通蛋白であるBP180が自己抗原となる．本症の自己抗体はIgGであり，その抗原との結合部位は，Ｈ鎖とＬ鎖の可変領域である．この部のアミノ酸の構成により，多種多彩の抗原が認識されるようになる．したがって，自己抗体の解析には，可変領域のアミノ酸配列が必須となるが,現在までに本症の自己抗体の可変領域を詳しく研究した報告はほとんどない．
本研究課題の核心をなす学術的な問いは，患者自己抗体の可変領域アミノ酸配列を明らかにすることであり，水疱性類天疱瘡の発症機構の解明や斬新な観点から治療法を開発するためには，自己抗体の解析は必要不可欠な問題と考える．

Outline of Final Research Achievements

Bullous pemphigoid (BP) is an autoimmune blistering disease (AIBD) characterized by subepidermal blisters and erosive lesions on the skin. Autoantibodies against the NC16a domain of BP180 in the epidermal basement membrane zone are produced in patients with BP. We use antiBP180-NC16a antibody titers as a marker of disease activity in outpatients with BP. We evaluated correlation to serum levels of antiBP180-NC16a antibodies and thymus and activation-regulated chemokine (TARC/CCL17). We studied the anti-BP180-type mucous membrane pemphigoid, epidermolysis bullosa acquisita, anti-laminin γ1 (p200) pemphigoid, and linear immunoglobulin A/immunoglobulin G bullous dermatosis. We studied the B-cell of BP patients by flow cytometry. We also examined autoantibodies to BPAG1e trigger experimental bullous pemphigoid in mice.

Academic Significance and Societal Importance of the Research Achievements

水疱性類天疱瘡（ＢＰ）は全身に表皮下水疱が多発する，最も頻度が高い自己免疫性水疱症であり，高齢者に好発する．本症患者の血清中には，皮膚の基底膜を認識する抗基底膜抗体が存在する．その自己抗体が認識する自己抗原として，BP230とBP180の類天疱瘡抗原が同定されたが1497アミノ酸からなるBP180のなかの非常に狭い領域，76アミノ酸からなるNC16aドメインを認識していることが解明されている．そこで，患者の抗BP180抗体の可変領域のアミノ酸配列を解析する研究を着想した．さらに，これが解明されれば，本症の自己抗体産生の発症機構の一端を明らかにできると考える．

Research Products

• [Journal Article] Conventional and Kampo Medicine Treatment for Mild-to-moderate COVID-19: A Multicenter, Retrospective, Observational Study by the Integrative Management in Japan for Epidemic Disease (IMJEDI Study-observation) (2023)
  • Author(s): Takayama S, Yoshino T, Koizumi S, Irie Y, Suzuki T, Fujii S, Kainuma M, Kobayashi S, Nogami T, Minakawa S, Ishige T, Maehara H, Tanaka Y, Nagase M, Kashio A, K Komatsu, Shimooki O, Nakamoto K, Arita R, Ono R, Saito N, Kikuchi A, Ohsawa M, Nakae H, Mitsuma T, Mimura M, Ishii T, Nochioka K, Chiu S, Yamaguchi T, et al
  • Journal Title: Internal Medicine Volume: 62 Issue: 2 Pages: 187-199
  • DOI: 10.2169/internalmedicine.0027-22
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2023-01-15
  • Peer Reviewed / Open Access
• [Journal Article] A Case of Anti-BP180-type Mucous Membrane Pemphigoid with IgG and IgA Autoantibodies Showing Distinct Reactivities. (2022)
  • Author(s): Minakawa S, Matsuzaki Y, Hashimoto T, Ishii N, Nishie W, Nakazawa M, Sawamura D.
  • Journal Title: Acta Dermatovenerol Croat Volume: 30 Pages: 54-56
  • Peer Reviewed / Open Access
• [Journal Article] Ultraviolet B irradiation leads to the development of experimental bullous pemphigoid targeting BPAG1e (2022)
  • Author(s): Kogawa Kazuhito、Matsuzaki Yasushi、Kimura Atsuko、Minakawa Satoko、Nakano Hajime、Ito Koichi、Kijima Hiroshi、Sawamura Daisuke
  • Journal Title: Journal of Dermatological Science Volume: 108 Issue: 2 Pages: 112-115
  • DOI: 10.1016/j.jdermsci.2022.12.001
  • Peer Reviewed / Open Access
• [Journal Article] A case of COVID‐19 with pernio‐like skin lesions and increased red blood cell distribution width (2022)
  • Author(s): Minakawa Satoko、Matsuzaki Yasushi、Terada Akari、Ogasawara Shu、Nishiya Yuki、Irie Jin、Ishizawa Yoshiya、Hanada Hiroyuki、Sawamura Daisuke
  • Journal Title: Journal of Cutaneous Immunology and Allergy Volume: 6 Issue: 2 Pages: 55-56
  • DOI: 10.1002/cia2.12272
  • Peer Reviewed / Open Access
• [Journal Article] Interhospital transmission of vancomycin-resistant Enterococcus faecium in Aomori, Japan (2022)
  • Author(s): Saito Norihiro、Kitazawa Junichi、Horiuchi Hiroko、Yamamoto Takeo、Kimura Masahiko、Inoue Fumio、Matsui Mika、Minakawa Satoko、Itoga Masamichi、Tsuchiya Junichiro、Suzuki Satowa、Hisatsune Junzo、Gu Yoshiaki、Sugai Motoyuki、Kayaba Hiroyuki
  • Journal Title: Antimicrobial Resistance & Infection Control Volume: 11 Issue: 1 Pages: 99-99
  • DOI: 10.1186/s13756-022-01136-5
  • Peer Reviewed / Open Access
• [Journal Article] Google Trends search volumes indicate habituation against COVID-19 in Japan. (2022)
  • Author(s): Minakawa S, Saito N, Itoga M, Kayaba H,
  • Journal Title: Hirosaki Med. J. Volume: 72 Pages: 1-4
  • Peer Reviewed / Open Access
• [Journal Article] Correlation between lactate dehydrogenase and other laboratory data in patients with atopic dermatitis (2022)
  • Author(s): Kogawa Kazuhito、Minakawa Satoko、Matsuzaki Yasushi、Okamoto Asumi、Ogasawara Shu、Saito Norihiro、Sawamura Daisuke
  • Journal Title: Journal of Cutaneous Immunology and Allergy Volume: - Issue: 4 Pages: 133-135
  • DOI: 10.1002/cia2.12225
  • Peer Reviewed / Open Access
• [Journal Article] A Case of Possible Concurrence of Dermatitis Herpetiformis and Linear Immunoglobulin A / Immunoglobulin G Bullous Dermatosis. (2021)
  • Author(s): Minakawa S, Matsuzaki Y, Hashimoto T, Ishii N, Nishie W, Sawamura D
  • Journal Title: Acta Dermatovenerol Croat. Volume: 29 Pages: 116-117
  • Peer Reviewed / Open Access
• [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] Hidradenitis suppurativa with perifolliculitis capitis abscedens et suffodiens successfully treated with a human anti‐tumour necrosis factor monoclonal antibody (2021)
  • Author(s): Minakawa S.、Matsuzaki Y.、Rokunohe D.、Kumagai N.、Kurose A.、Kushibiki M.、Kayaba H.、Sawamura D.
  • Journal Title: Clinical and Experimental Dermatology Volume: 46 Issue: 8 Pages: 1586-1588
  • DOI: 10.1111/ced.14789
  • Peer Reviewed
• [Journal Article] Atypical eosinophilic annular erythema clinically resembling granuloma annulare (2021)
  • Author(s): Matsuzaki Yasushi、Minakawa Satoko、Sagara Chihiro、Matsui Akinobu、Nakano Hajime、Sawamura Daisuke
  • Journal Title: International Journal of Dermatology Volume: 60 Issue: 10
  • DOI: 10.1111/ijd.15591
  • Peer Reviewed / Open Access
• [Journal Article] Serum 3-Hydroxybutyrate in Patients with Psychogenic Somatoform Symptoms May Be a Predictor of the Effectiveness of Sertraline and Venlafaxine (2021)
  • Author(s): Saito Norihiro、Itoga Masamichi、Minakawa Satoko、Kayaba Hiroyuki
  • Journal Title: International Journal of General Medicine Volume: Volume 14 Pages: 1785-1795
  • DOI: 10.2147/ijgm.s300517
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between red blood cell aging and intracellular chemokine storage (2021)
  • Author(s): Ogasawara S, Saito N, Minakawa S, Akasaki T, Kayaba H
  • Journal Title: Hirosaki Med. J. Volume: 71 Pages: 113-119
  • NAID: 130007998248
  • Peer Reviewed / Open Access
• [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] Impact of Geographical Variations on the Prevalence of Multidrug-Resistant Organisms in Japan (2020)
  • Author(s): Saito N, Minakawa S, Inoue F, Kimura M, Ogasawara S, Kayaba H.
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 73 Issue: 5 Pages: 354-360
  • DOI: 10.7883/yoken.JJID.2019.498
  • NAID: 130007907142
  • ISSN: 1344-6304, 1884-2836
  • Year and Date: 2020-09-30
  • Open Access
• [Journal Article] Nondestructive Evaluations of Melanin-related Compounds in the Skin Using Electron Paramagnetic Resonance and Permeability Measurements (2020)
  • Author(s): K. Nakagawa*, S. Minakawa, and D. Sawamura
  • Journal Title: Analytical Sciences Volume: 36 Issue: 7 Pages: 865-869
  • DOI: 10.2116/analsci.20P001
  • NAID: 130007872127
  • ISSN: 0910-6340, 1348-2246
  • Year and Date: 2020-07-10
  • Peer Reviewed / Open Access
• [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] Clinical relevance of procalcitonin values in bacteremia. (2020)
  • Author(s): Ogasawara S, Saito N, Hirano R, Minakawa S, Kimura M, Kayaba H.
  • Journal Title: J Infect Chemother. Volume: 26 Issue: 10 Pages: 1048-1053
  • DOI: 10.1016/j.jiac.2020.05.023
  • 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
• [Presentation] Possible correlation of serum anti-BP180-NC16a antibody and thymus and activation-regulated chemokine in patients with bullous pemphigoid. (2023)
  • Author(s): Minakawa S, Matsuzaki Y, Sawamura D,
  • Organizer: The 2023 Annual Meeting of the American Academy of Dermatology
  • Int'l Joint Research
• [Presentation] Correlation between lactate dehydrogenase and total IgE levels, TARC levels, and eosinophil count in patients with atopic dermatitis. (2023)
  • Author(s): Minakawa S, Kogawa K, Matsuzaki Y, Okamoto A, Ogasawara S, Saito N, Sawamura D
  • Organizer: The 2023 Annual Meeting of the American Academy of Dermatology
  • Int'l Joint Research
• [Presentation] 先天性縮毛症/乏毛症の1例 (2022)
  • Author(s): 皆川智子，松崎康司，中野 創，澤村大輔, 山谷 眞吾,
  • Organizer: 皮膚かたち研究学会 第48回学術大会
• [Presentation] 母乳中Anti-SARS-CoV-2-specific IgAとIgGを測定したCOVID-19の1例 (2022)
  • Author(s): 皆川智子，小笠原 脩，赤崎友美，櫛引美穂子，蔦谷昭司，石山 雅大，土屋 純一郎，糸賀正道，齋藤紀先，富田泰史.
  • Organizer: 第69回日本臨床検査医学会学術集会
• [Presentation] 水痘を発症した皮膚筋炎の1例 (2022)
  • Author(s): 皆川智子，松﨑康司，山下あや，六戸亜希子，中野 創，澤村大輔，平賀寛人
  • Organizer: 日本皮膚科学会 第400回日本皮膚科学会青森地方会
• [Presentation] 膿疱性乾癬の1例. (2022)
  • Author(s): 皆川智子，松﨑康司，吉川未雪，六戸大樹，赤坂英二郎，中野創，澤村大輔, 大門 眞，野村和夫，渡邊総一郎，杉浦一充.
  • Organizer: 日本人類遺伝学会第67回大会
• [Presentation] 半夏厚朴湯が有用であった咽喉頭異常感症の1例 (2022)
  • Author(s): 皆川 智子, 新谷 哲一
  • Organizer: 第72回日本東洋医学会学術総会
• [Presentation] Mutations in FLG, the gene-coding profilaggrin/filaggrin, are associated with putative hay fever in patients with atopic dermatitis. (2022)
  • Author(s): Minakawa S, Matsuzaki Y, Suwa H, Kono M, Akiyama M, Sawamura D
  • Organizer: The 2022 Annual Meeting of the American Academy of Dermatology
  • Int'l Joint Research
• [Presentation] 化膿性汗腺炎の1例 (2021)
  • Author(s): 皆川智子, 松崎康司, 六戸大樹, 中野 創, 澤村 大輔
  • Organizer: 日本皮膚科学会 青森地方会第393回例会
• [Presentation] 十味敗毒湯を併用した毛巣洞の2例 (2021)
  • Author(s): 皆川 智子, 新谷 哲一
  • Organizer: 第71回日本東洋医学会学術総会
• [Presentation] 日本においてCOVID-19に関するグーグル検索数はCOVID-19の流行の大きさと逆相関した (2021)
  • Author(s): 皆川智子，齋藤紀先，糸賀正道，土屋純一郎，小笠原 脩，萱場広之
  • Organizer: 第68回日本臨床検査医学会学術集会
• [Presentation] バリシチニブ内服後痒みが改善したアトピー性皮膚炎の2例 (2021)
  • Author(s): 皆川智子，松﨑康司，六戸大樹，中野 創，澤村大輔
  • Organizer: 日本皮膚科学会 青森地方会第396回例会
• [Presentation] 凍瘡様皮疹を呈したCOVID-19の1例 (2021)
  • Author(s): 皆川智子, 松﨑康司, 中野 創, 西谷佑希, 石澤義也, 入江仁,花田裕之, 澤村大輔
  • Organizer: 第159回弘前医学会例会
• [Presentation] 線状IgA水疱性皮膚症の1例 (2020)
  • Author(s): 皆川智子, 松崎康司, 中野 創, 澤村大輔, 萱場広之, 松木哲文, 西江 渉，石井文人, 橋本 隆.
  • Organizer: 日本皮膚科学会 青森地方会第391回例会
• [Presentation] Dipeptidyl peptidase-Ⅳ阻害薬関連水疱性類天疱瘡と鑑別を要した抗ラミニンγ1類天疱瘡の1例, (2020)
  • Author(s): 皆川智子, 松崎康司, 中野 創, 澤村大輔, 萱場広之, 西江 渉, 石井文人, 橋本 隆.
  • Organizer: 第41回水疱症研究会(2020/1/11)
• [Presentation] アトピー性皮膚炎患者におけるフィラグリン遺伝子変異とTARCの検討 (2020)
  • Author(s): 皆川智子, 小笠原 脩, 斎藤紀先, 萱場広之,
  • Organizer: 第67回日本臨床検査医学会学術集会
• [Presentation] 日本円における微生物の生残性の検討 (2020)
  • Author(s): 皆川智子, 照井緋奈乃, 小笠原 脩, 斎藤紀先, 萱場広之
  • Organizer: 第67回日本臨床検査医学会学術集会
• [Presentation] Melanin radicals in paraffin-embedded melanoma and nevus pigmentosus using X-band EPR and EPR imaging. (2020)
  • Author(s): Minakawa S, Nakagawa K, Kaneko T, Rokunohe D, Sawamura D
  • Organizer: The 24th International Pigment Cell Conference (IPCC2020)
• [Remarks] 弘前大学大学院医学研究科皮膚科学講座
  • URL: https://hirosaki-u-hifuka.jp/
• [Remarks] 弘前大学医学部医学研究科 皮膚科学講座
  • URL: https://hirosaki-u-hifuka.jp/