Study of sweat allergy development and mast cell activation mechanism

2023 Fiscal Year Annual Research Report

• Project/Area Number: 21K08346
• Research Institution: Hiroshima University
• Principal Investigator: 秀 道広 広島大学, 医系科学研究科(医), 名誉教授 (50284188)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 汗アレルギー / 角化細胞 / コリン性蕁麻疹 / クラウディン3 / サイトカイン / 組織因子 / 皮膚バリア

Outline of Annual Research Achievements

本研究では、コリン性蕁麻疹における汗アレルギーによる皮膚マスト細胞の活性化と、血液凝固能亢進という特発性の蕁麻疹との共通病態に加え、コリン性蕁麻疹とアトピー性皮膚炎における汗アレルギーの関与という共通点に着目し、ヒスタミンおよび炎症サイトカインによる血管内皮細胞の組織因子発現誘導の時間経過と皮膚組織内に漏れ出た汗が皮膚構成細胞に及ぼす影響に着目して研究を進めた。
まずヒト臍帯血静脈血管内皮細胞の組織因子発現誘導に及ぼすヒスタミンと炎症性サイトカインの作用動態について、必ずしも両者が同時ではなくても、いずれかが曝露後12時間程度の時間差で他方の因子が作用することでも組織因子が誘導されることを明らかにした。皮膚組織内に漏れ出た汗の影響については、汗腺上皮細胞のバリア機能蛋白であるclaudin-3をノックアウトしたマウスに加え、in vivoでの血管内皮細胞上の組織因子発現を解析するための手段として、組織因子遺伝子にYFP蛍光蛋白遺伝子をノックインしたマウスを作出した。次にヒト汗を培養角化細胞および線維芽細胞に添加して発現誘導されるトランスクリプトーム解析を行い、ヒト汗には表皮角化細胞と線維芽細胞に異なる起炎性サイトカインとともに、皮膚バリア機能を担う蛋白産生を抑制するサイトカインの発現を誘導する活性があることを明らかにした。また、発汗神経から遊離されると考えられるVIP,CGRP等の神経ペプチドと、抗菌ペプチドのLL-37、βdefencinはヒト皮膚マスト細胞からのヒスタミンを遊離したが、汗中のdermcidinにはそれらの活性は見られなかった。
今後、これらの汗の生物活性の本体を同定し、皮膚組織内に漏れ出た場合にどのように挙動するかということを解析することで、汗による蕁麻疹ならびにアトピー性皮膚炎の病態形成を明らかにすることが期待される。

Research Products

• [Int'l Joint Research] Charitie Universitaetsmedizin(ドイツ)
  • Country Name: GERMANY
  • Counterpart Institution: Charitie Universitaetsmedizin
• [Journal Article] Retrospective Evaluation of an Oral Propranolol Delivery Strategy in 25 Cases of Infantile Hemangioma (2024)
  • Author(s): Ashizawa Shinichi、Kan Takanobu、Takahagi Shunsuke、Kawai Mikio、Toda Sayuri、Iwasaki Yasumasa、Karakawa Shuhei、Hide Michihiro、Tanaka Akio
  • Journal Title: Journal of Plastic and Reconstructive Surgery Volume: 3 Pages: 94～98
  • DOI: 10.53045/jprs.2023-0016
  • Peer Reviewed
• [Journal Article] Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials (2024)
  • Author(s): Maurer M, Ensina LF, Gimenez-Arnau AM, Sussman G, Hide M, Saini S, Grattan C, Fomina D, Rigopoulos D, Berard F, Canonica GW, Rockmann H, Irani C, Szepietowski JC, Leflein J, Bernstein JA, Peter JG, Kulthanan K, Godse K, Ardusso L, Ukhanova O, Staubach P, Sinclair R, Gogate S, Thomsen SF, Tanus T, Ye YM, et al.
  • Journal Title: The Lancet Volume: 403 Pages: 147～159
  • DOI: 10.1016/S0140-6736(23)01684-7
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] CRUSE(R) - An innovative mobile application for patient monitoring and management in chronic spontaneous urticaria (2024)
  • Author(s): Neisinger S, Sousa Pinto B, Ramanauskaite A, Bousquet J, Weller K, Metz M, Magerl M, Kocaturk E, Cherrez-Ojeda I, Gimenez-Arnau AM, Parisi CAS, Altrichter S, Ensina LF, Bouillet L, Asero R, Goncalo M, Guillet C, Rutkowski K, Bernstein JA, Hardin H, Godse K, Brzoza Z, Sousa JIL, Thomsen SF, Hide M, et al.
  • Journal Title: Clinical and Translational Allergy Volume: 14 Pages: e12328
  • DOI: 10.1002/clt2.12328
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Analysis of questionnaire survey to determine worldwide trends in prescriptions of biologics for the treatment of unresponsive chronic urticaria (2024)
  • Author(s): Rubeiz Christine J.、Asero Ricardo、Betschel Stephen、Craig Timothy、Grumach Anete、Hide Michihiro、Lang David、Levin Michael、Longhurst Hilary、Magan Eli、Maurer Marcus、Saini Romi、Sussman Gordon、Toubi Elias、Van Dinh Nguyen、Zuberier Torsten、Bernstein Jonathan A.
  • Journal Title: World Allergy Organization Journal Volume: 17 Pages: 100858～100858
  • DOI: 10.1016/j.waojou.2023.100858
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Berotralstat for long-term prophylaxis of hereditary angioedema in Japan: Parts 2 and 3 of the randomized APeX-J Phase III trial (2024)
  • Author(s): Honda Daisuke、Hide Michihiro、Fukuda Tomoo、Koga Keisuke、Morita Eishin、Moriwaki Shinichi、Sasaki Yoshihiro、Suzuki Yusuke、Collis Phil、Johnston Douglas T.、Tomita Dianne、Desai Bhavisha、Ohsawa Isao
  • Journal Title: World Allergy Organization Journal Volume: 17 Pages: 100882～100882
  • DOI: 10.1016/j.waojou.2024.100882
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Survey of hereditary angioedema episodes and quality of life impairment through a patient-participatory registry (2024)
  • Author(s): Morioke Satoshi、Aikyo Tatsuki、Tanaka Akio、Matsubara Daiki、Saito Ryo、Iwamoto Kazumasa、Yamasaki Chisato、Kogetsu Atsushi、Hamakawa Nao、Isono Moeko、Yamamoto Beverley Anne、Matsumura Yasushi、Takeda Toshihiro、Manabe Shiro、Javaid Muhammad Kassim、Barrett Joe、Gray Nathanael、Kaye Jane、Kato Kazuto、Hide Michihiro
  • Journal Title: Journal of Cutaneous Immunology and Allergy Volume: 7 Pages: －
  • DOI: 10.3389/jcia.2024.12626
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 遺伝性血管性浮腫 (2024)
  • Author(s): 秀 道広
  • Journal Title: 皮膚科 Volume: 5 Pages: 42-50
• [Journal Article] Basophil Characteristics as a Marker of the Pathogenesis of Chronic Spontaneous Urticaria in Relation to the Coagulation and Complement Systems (2023)
  • Author(s): Yanase Yuhki、Matsubara Daiki、Takahagi Shunsuke、Tanaka Akio、Ozawa Koichiro、Hide Michihiro
  • Journal Title: International Journal of Molecular Sciences Volume: 24 Pages: 10320～10320
  • DOI: 10.3390/ijms241210320
  • Peer Reviewed / Open Access
• [Journal Article] Pustular eruption on the palms and soles associated with zinc allergy and perspiration (2023)
  • Author(s): Naito Yukiko、Matsumura Shunji、Hada Yoshinori、Tanaka Maiko、Takahagi Shunsuke、Hide Michihiro
  • Journal Title: JAAD Case Reports Volume: 36 Pages: 92～95
  • DOI: 10.1016/j.jdcr.2023.04.012
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy, pharmacokinetics, and safety of subcutaneous C1-esterase inhibitor as prophylaxis in Japanese patients with hereditary angioedema: Results of a Phase 3 study (2023)
  • Author(s): Fukuda Tomoo、Yamagami Keiko、Kawahata Kimito、Suzuki Yuzo、Sasaki Yoshihiro、Miyagi Takashi、Jacobs Iris、Lawo John-Philip、Glassman Fiona、Akama Hideto、Hide Michihiro、Ohsawa Isao
  • Journal Title: Allergology International Volume: 72 Pages: 451～457
  • DOI: 10.1016/j.alit.2023.02.002
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A single-blind, randomized, crossover study on the efficacy of icatibant for sweating-induced dermal pain (icatibant for sweating-induced dermal pain) (2023)
  • Author(s): Takahagi Shunsuke、Hide Michihiro、Aoyama Yumi、Fukunaga Atsushi、Murota Hiroyuki
  • Journal Title: Medicine Volume: 102 Pages: e33971～e33971
  • DOI: 10.1111/1346-8138.16883
  • Peer Reviewed / Open Access
• [Journal Article] Safety, efficacy, and pharmacokinetics of icatibant treatment in Japanese pediatric patients with hereditary angioedema: A phase 3, open‐label study (2023)
  • Author(s): Hide Michihiro、Wang Yi、Dote Nobuhito、Miyakawa Kou、Sugiura Kenkichi、Ishida Kazuyuki
  • Journal Title: The Journal of Dermatology Volume: 50 Pages: 1473～1477
  • DOI: 10.1016/j.alit.2022.09.003
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Real-world safety and effectiveness of omalizumab in Japanese patients with chronic spontaneous urticaria: A post-marketing surveillance study (2023)
  • Author(s): Hide Michihiro、Fukunaga Atsushi、Suzuki Takayuki、Nakamura Noriko、Kimura Mine、Sasajima Takayoshi、Kiriyama Junna、Igarashi Atsuyuki
  • Journal Title: Allergology International Volume: 72 Pages: 286～296
  • DOI: 10.1111/1346-8138.16909
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy and safety of lanadelumab in Japanese patients with hereditary angioedema: A phase 3 multicenter, open‐label study (2023)
  • Author(s): Hide Michihiro、Ohsawa Isao、Nurse Christina、Yu Ming、for the SHP643‐302 Trial Investigators
  • Journal Title: The Journal of Dermatology Volume: 50 Pages: 1381～1391
  • DOI: 10.3390/ijms241512388
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Time Course of Priming Effect of TF Inducers on Synergistic TF Expression and Intra-Cellular Gap Formation of Human Vascular Endothelial Cells via the Extrinsic Coagulation Cascade (2023)
  • Author(s): Matsubara Daiki、Kunieda Takuma、Yanase Yuhki、Takahagi Shunsuke、Uchida Kazue、Kawaguchi Tomoko、Ishii Kaori、Tanaka Akio、Ozawa Koichiro、Hide Michihiro
  • Journal Title: International Journal of Molecular Sciences Volume: 24 Pages: 12388～12388
  • DOI: 10.1111/1346-8138.16932
  • Peer Reviewed / Open Access
• [Journal Article] English version of Japanese guidance for biologics in treating atopic dermatitis (2023)
  • Author(s): Saeki Hidehisa、Akiyama Masashi、Abe Masatoshi、Igarashi Atsuyuki、Imafuku Shinichi、Ohya Yukihiro、Katoh Norito、Kameda Hideto、Kabashima Kenji、Tsunemi Yuichiro、Hide Michihiro、Ohtsuki Mamitaro、Committee for reviewing the safety of atopic dermatitis/urticaria treatment, Japanese Dermatological Association
  • Journal Title: The Journal of Dermatology Volume: 50 Pages: e311-e322
  • DOI: 10.1111/1346-8138.16635
  • Peer Reviewed / Open Access
• [Journal Article] A concept for integrated care pathways for atopic dermatitis -AGA(2)LEN ADCARE initiative (2023)
  • Author(s): Zuberbier T, Abdul Latiff A, Aggelidis X, Augustin M, Balan RG, Bangert C, Beck L, Bieber T, Bernstein JA, Bertolin Colilla M, Berardi A, Bedbrook A, Bindslev-Jensen C, Bousquet J, de Bruin-Weller M, Bruscky D, Buyuktiryaki B, Canonica GW, Castro C, Chanturidze N, Chong-Neto HJ, Chu CY, … Hide M, et al.
  • Journal Title: Clinical and Translational Allergy Volume: 13 Pages: e12299
  • DOI: 10.1002/clt2.12299
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mathematical-based morphological classification of skin eruptions corresponding to the pathophysiological state of chronic spontaneous urticaria (2023)
  • Author(s): Seirin-Lee Sungrim、Matsubara Daiki、Yanase Yuhki、Kunieda Takuma、Takahagi Shunsuke、Hide Michihiro
  • Journal Title: Communications Medicine Volume: 3 Pages: 171
  • DOI: 10.1038/s43856-023-00404-8
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy and safety of omalizumab in adult patients with wheat-dependent exercise-induced anaphylaxis: Reduction of in vitro basophil activation and allergic reaction to wheat (2023)
  • Author(s): Chinuki Yuko、Kohno Kunie、Hide Michihiro、Hanaoka Keiko、Okabe Takahiro、Fukunaga Atsushi、Oda Yoshiko、Adachi Atsuko、Ugajin Tsukasa、Yokozeki Hiroo、Suzuki Ritsuro、Sugiyama Akiko、Kishikawa Reiko、Yamasaki Osamu、Morita Eishin
  • Journal Title: Allergology International Volume: 72 Pages: 444～450
  • DOI: 10.1016/j.alit.2022.11.013
  • Peer Reviewed / Open Access
• [Journal Article] WAO/EAACI遺伝性血管性浮腫診療ガイドライン-2017年改訂版 (2023)
  • Author(s): 秀 道広、大澤 勲、福永 淳、山下浩平、田中 彰、鈴木大士、本田大介、田中暁生、パワンカール ルビー
  • Journal Title: アレルギー Volume: 72 Pages: 158-183
  • Peer Reviewed / Open Access
• [Journal Article] WAO/EAACI遺伝性血管性浮腫診療ガイドライン-2021年改訂版 (2023)
  • Author(s): 森桶 聡、田中暁生、松原大樹、大澤 勲、福永 淳、山下浩平、齋藤 怜、田中 彰、本田大介、パワンカールルビー、秀 道広
  • Journal Title: アレルギー Volume: 72 Pages: 237-272
  • Peer Reviewed / Open Access
• [Journal Article] 蕁麻疹新時代の夜明け (2023)
  • Author(s): 秀 道広
  • Journal Title: アレルギーの臨床 Volume: 43 Pages: 915-915
• [Journal Article] アトピー性皮膚炎における生物学的製剤の使用ガイダンス (2023)
  • Author(s): 椛島 健治、常深 祐一郎、秀 道広、大槻 マミ太郎、佐伯 秀久、秋山 真志、安部 正敏、五十嵐 敦之、今福 信一、大矢 幸弘、加藤 則人、亀田 秀人
  • Journal Title: 日本皮膚科学会雑誌 Volume: 133 Pages: 1817～1827
  • DOI: 10.14924/dermatol.133.1817
  • Peer Reviewed
• [Presentation] 急性蕁麻疹治癒率の経時変化に関する数学的解析 (2024)
  • Author(s): 秀 道広,田中稔彦,高萩俊輔, 李 聖林
  • Organizer: 日本皮膚科学会第154回広島地方会
• [Presentation] Understanding mediators, mechanisms and inflammation pathways in chronic spontaneous urticaria helps us to treat our patients (2023)
  • Author(s): Michihiro Hide
  • Organizer: 25th World Congress of Dermatology Singapore 2023
  • Int'l Joint Research / Invited
• [Presentation] Diagnostic Challenges in HAE (2023)
  • Author(s): Michihiro Hide
  • Organizer: APAAACI2023
  • Int'l Joint Research / Invited
• [Presentation] Acute urticaria: are there differences in pathogenesis and treatment? How often does it develop into chronic urticaria? Epidemiological analysis and effect of proactive treatment with antihistamine (2023)
  • Author(s): Michihiro Hide
  • Organizer: UCARE2023
  • Int'l Joint Research / Invited
• [Presentation] Results From a Randomized, Double-Blind, Placebo-Controlled, Phase 1 Trial Evaluating Sebetralstat Pharmacokinetics, Pharmacodynamics, and Safety/Tolerability in Healthy Japanese, Chinese, and White Adults (2023)
  • Author(s): Michihiro Hide, Matthew Iverson, Stanford Jhee, Erik Hansen, Edward J. Duckworth, Sally L. Hampton, Esther Yoon, Daisuke Honda
  • Organizer: European Academy of Allergy and Clinical Immunology Hybrid Congress 2023
  • Int'l Joint Research
• [Presentation] Investigating On-Demand Use of Oral Sebetralstat in Adults and Adolescents With Hereditary Angioedema: Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase 3 KONFIDENT Trial and Open-Label Extension Designs (2023)
  • Author(s): Michihiro Hide, Paul K Audhya, Michael D Smith, Christopher M Yea
  • Organizer: 第72回日本アレルギー学会総会
  • Int'l Joint Research
• [Presentation] CholU-CE：Cholinergic urticaria - a comprehensive evaluation of natural history, disease features and course and response to treatment (2023)
  • Author(s): Michihiro Hide, Eva Maria Grekowitz, Sabine Altrichter, Torsten Zuberbier, Eva Maria Grekowitz, Sabine Altrichter, Torsten Zuberbier, Michihiro Hide, Chris Rutkowski, Ivan Cherrez, Sofia Cherrez, Michael Makris, Mona Al-Ahmad, Eva Grekowitz
  • Organizer: UCARE2023
  • Int'l Joint Research
• [Book] Handbook on Angioedema (2023)
  • Author(s): Fukunaga A, Yoshiko Oda Y, Shunsuke Takahagi S, Hide M.
  • Total Pages: 210
  • Publisher: JAYPEE BROTHERS MEDICAL PUBLISHERS PVT.LTD
  • ISBN: 978-9356961647