TAKAHASHI Hayato

写真a

Affiliation

School of Medicine, Department of Dermatology (Shinanomachi)

Position

Associate Professor

Academic Background 【 Display / hide

  • 1994.04
    -
    2000.03

    慶應義塾大学, 医学部

    日本, University, Graduated

  • 2002.04
    -
    2006.03

    慶應義塾大学大学院, 医学研究科, 内科系皮膚科学

    Graduate School, Withdrawal after completion of doctoral course requirements, Doctoral course

Academic Degrees 【 Display / hide

  • 博士(医学), 慶應義塾大学, Coursework, 2009.01

    Novel system evaluating in vivo pathogenicity of desmoglein 3-reactive T cell clones using murine pemphigus vulgaris.

Licenses and Qualifications 【 Display / hide

  • 医師免許, 2000.04

  • 日本皮膚科学会認定皮膚科専門医, 2007.10

 

Research Areas 【 Display / hide

  • Dermatology

  • Immunology

Research Keywords 【 Display / hide

  • Desmoglein

  • Pemphigus

  • Interface dermatitis

  • Drug eruption

  • Food allergy

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Books 【 Display / hide

  • 眼疾患アトラスシリーズ 第3巻『外眼部アトラス』

    高橋勇人, 総合医学社, 2019.10

    Scope: 丹毒,  Contact page: 108-109

  • 皮膚科のくすりの使い方

    高橋勇人, じほう, 2019.08

    Scope: 薬疹,  Contact page: 141-144

  • 私の治療2019-20年度

    高橋勇人, 日本医事新報社, 2019.07

    Scope: 天疱瘡,  Contact page: 877-878

  • ガイドライン外来診療 2019

    高橋勇人, 日経メディカル開発, 2019.03

    Scope: 薬疹,  Contact page: 329-334

  • 皮膚症状110症例でみる内科疾患

    高橋勇人, 日本医事新報社, 2018.09

    Scope: 悪性リンパ腫③ 腫瘍随伴性天疱瘡,  Contact page: 22-23

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Papers 【 Display / hide

  • Basement membrane zone IgE deposition is associated with bullous pemphigoid disease severity and treatment results

    Basement membrane zone IgE deposition is associated with bullous pemphigoid disease severity and treatment results

    British Journal of Dermatology 182 ( 5 ) 1221 - 1227 2020.05

    Joint Work, Accepted,  ISSN  00070963

     View Summary

    © 2019 British Association of Dermatologists Background: A subset of patients with bullous pemphigoid (BP) show deposition of IgE in the basement membrane zone (BMZ), yet the relationship between BMZ IgE and the clinical presentation of BP remains unclear. Objectives: To investigate the relationship between IgE deposition, IgE levels in serum, and disease severity in patients with BP. Methods: We investigated IgE autoantibodies in 53 patients with BP by direct immunofluorescence (DIF), indirect immunofluorescence and enzyme-linked immunosorbent assay. Results: Of 53 patients with BP, 23 (43%) had IgE deposition, 10 (19%) of whom were IgE+ and 13 (25%) IgE± according to DIF analyses. Erosion/blister (E/B) Bullous Pemphigoid Disease Area Index (BPDAI) scores were significantly higher in IgE+ patients than in IgE− patients (n = 15), while no significant differences were found for urticaria/erythema BPDAI scores. IgE+ and IgE± patients took longer to reduce their E/B BPDAI score by 75% after systemic corticosteroid treatment. BP180-IgE levels were significantly higher among IgE+ patients than IgE± or IgE− patients (n = 10). Total IgE levels in the serum and blood eosinophil counts did not differ between IgE+, IgE± and IgE− patients. A significant correlation was detected between BP180-IgG and BP180-IgE, but not between BPDAI scores and any of BP180-IgG, BP180-IgE or blood eosinophil count. Conclusions: IgE deposition in the BMZ is associated with higher E/B BPDAI scores and longer treatment periods. We conclude that IgE binding in the BMZ may contribute to BP pathogenesis by promoting blister formation. What's already known about this topic?. BP180-IgE autoantibodies have an important role in the pathogenesis of bullous pemphigoid (BP). A subset of patients with BP display deposition of IgE within the basement membrane zone (BMZ) of skin tissue. What does this study add?. Patients with in vivo IgE deposition in the BMZ displayed higher erosion/blister Bullous Pemphigoid Disease Area Index (BPDAI) scores, while urticaria/erythema BPDAI scores were not significantly different. Patients with in vivo IgE deposition in the BMZ took longer to reduce their erosion/blister BPDAI score by 75% after systemic corticosteroid treatment. BP180-specific IgE levels in serum were higher among patients with linear IgE deposition in the BMZ than in those with granular or no IgE deposition.

  • Successful treatment with secukinumab of three psoriatic patients undergoing dialysis

    Mukai M, Kurihara Y, Ito Y, Shintani Y, Takahashi H, Kubo A, Amagai M, Umegaki-Arao N

    (J Dermatol)  47 ( 1 ) e26 - e28 2020.01

    Joint Work, Accepted,  ISSN  0385-2407

  • Development of an electronic medical record-based algorithm to identify patients with Stevens-Johnson syndrome and toxic epidermal necrolysis in Japan

    Fukasawa T., Takahashi H., Kameyama N., Fukuda R., Furuhata S., Tanemura N., Amagai M., Urushihara H.

    PLoS ONE (PLoS ONE)  14 ( 8 ) e0221130 2019.08

    Joint Work, Accepted,  ISSN  1932-6203

     View Summary

    © 2019 Fukasawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), severe drug reactions, are often misdiagnosed due to their rarity and lack of information on differential diagnosis. The objective of the study was to develop an electronic medical record (EMR)-based algorithm to identify patients with SJS/TEN for future application in database studies. From the EMRs of a university hospital, two dermatologists identified all 13 patients with SJS/TEN seen at the Department of Dermatology as the case group. Another 1472 patients who visited the Department of Dermatology were identified using the ICD-10 codes for diseases requiring differentiation from SJS/TEN. One hundred of these patients were then randomly sampled as controls. Based on clinical guidelines for SJS/TEN and the experience of the dermatologists, we tested 128 algorithms based on the use of ICD-10 codes, clinical courses for SJS/TEN, medical encounters for mucocutaneous lesions from SJS/TEN, and items to exclude paraneoplastic pemphigus. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic odds ratio (DOR) of each algorithm were calculated, and the optimal algorithm was defined as that with high PPV and maximal sensitivity and specificity. One algorithm, consisting of a combination of clinical course for SJS/TEN, medical encounters for mucocutaneous lesions from SJS/TEN, and items to exclude paraneoplastic pemphigus, but not ICD-10 codes, showed a sensitivity of 76.9%, specificity of 99.0%, PPV of 40.5%, NPV of 99.8%, and DOR of 330.00. We developed a potentially optimized algorithm for identifying SJS/TEN based on clinical practice records. The almost perfect specificity of this algorithm will prevent bias in estimating relative risks of SJS/TEN in database studies. Considering the small sample size, this algorithm should be further tested in different settings.

  • Autoimmunity and immunological tolerance in autoimmune bullous diseases

    Takahashi H., Iriki H., Mukai M., Kamata A., Nomura H., Yamagami J., Amagai M.

    International immunology (International immunology)  31 ( 7 ) 431 - 437 2019.07

    Joint Work, Accepted,  ISSN  0953-8178

     View Summary

    © The Japanese Society for Immunology. 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Autoimmune diseases are devastating conditions in which the immune system is directed against the host, leading to life-threatening destruction of organs. Although autoantigens are ill-defined in most autoimmune diseases, this is not the case in the skin. Autoimmune bullous diseases have been extensively studied with detailed characterization of autoantigens, the epitopes that are targeted, and the mechanisms of action that mediate autoimmune tissue destruction. Pemphigus is an autoimmune bullous disease caused by circulating IgG that targets two desmosomal proteins, desmoglein 1 and 3, which are crucial for cell-cell adhesion of keratinocytes. Binding of auto-antibodies to desmogleins impairs keratinocyte adhesion, leading to severe blistering disease. Mouse models that recapitulate the human disease have been instrumental in elucidating the detailed pathophysiology. Taking advantage of the fact that desmogleins are specifically targeted in pemphigus, studying humoral and cellular autoimmunity against these autoantigens provides us with an opportunity to understand not only the effector mechanisms of B and T cells in mediating pathology but also how autoreactive lymphocytes are regulated during development in the thymus and post-development in the periphery. This review introduces pemphigus and its subtypes as prototypic autoimmune diseases from which recent basic and translational developments should provide insight into how autoimmunity develops.

  • 好酸球増多症と多発性単神経炎,紫斑を伴った末梢性T細胞リンパ腫非特定型の1例

    柳澤絵里加, 栗原佑一, 舩越建, 高橋勇人, 加野美希, 深井達夫, 戸澤圭一, 清水隆之, 天谷雅行, 海老原全

    臨床皮膚科 73 ( 6 ) 457 - 464 2019.05

    Joint Work, Accepted,  ISSN  0021-4973

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

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Presentations 【 Display / hide

  • IL-27 is crucial in anti-desmoglein 3 autoantibody production in pemphigus vulgaris mouse model

    Kamata A, Takahashi H, Yoshida H, Yamagami J, Amagai M

    48th Annual Meeting of the Japanese Society for Immunology (Hamamatsu, Japan) , 2019.12

  • Blockade of pathogenic immunoglobulin class-switch is a tolerogenic process to prevent pemphigus development in desmoglein 3-sepecific B cell receptor knock-in mouse

    Nomura H, Takahashi H, Yamagami J, Fujii H, Koseki H, Watanabe T, Ohara O, Koyasu S, Amagai M

    48th Annual Meeting of The Japanese Society for Immunology (Hamamatsu, Japan) , 2019.12

  • The clinical utility of basophil activation test in diagnosis of hypersensitivity due to fermented soybeans,natto

    Fukuda R, Ouchi T, Shiiya C, Yasuda-Sekiguchi F, Kouno M, Takahashi S, Amagai M, Takahashi H

    EAACI Allegy School on Food Allergy (Paris, France) , 2019.12

  • 薬疹 経過中に自己抗体が出現した薬剤性過敏症症候群および疑い例の検討

    椎谷千尋, 大内健嗣, 舩越建, 天谷雅行, 高橋勇人

    第49回日本皮膚免疫アレルギー学会総会学術大会 (横浜) , 2019.11

  • Evaluation on cytokine and transcriptional factor impacts on cholesterol 25-hydroxylase induction in CD4+ T cells

    Takahashi H, Isami K, Amagai M

    44th Annual Meeting of the Japanese Society for Investigative Dermatology (Aomori, Japan) , 2019.11

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • [基盤研究A] 病態に直結するT細胞レパトアの制御を目指した、新たな免疫制御機構の同定と解析

    2019.04
    -
    2023.03

    基盤研究A, 高橋勇人, Research grant, Principal Investigator

  • [慶應義塾・学事振興資金(個人研究 特B)]天疱瘡自己抗原に対する末梢性免疫寛容機構の解明

    2018.04
    -
    2019.03

    慶應義塾学事振興資金

  • [革新的先端研究開発支援事業] PRIME 新規T細胞サブセットを規定するコレルテロール代謝酵素の機能解析と疾患制御への応用

    2016
    -
    2019

    AMED(国立研究開発法人日本医療研究開発機構)-PRIME, 高橋勇人

  • [免疫アレルギー疾患等実用化研究事業 免疫アレルギー疾患実用化研究分野] 重症薬疹サンプルの選定、採取およびウィルス叢と疾患発症との関連性解析

    2015
    -
    Present

    AMED(国立研究開発法人日本医療研究開発機構), 阿部 理一郎, Co-investigator

  • Molecular mechanism of skin inflammation induced by desmoglein 3-specific T cells

    2014.04
    -
    2017.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 高橋 勇人, Grant-in-Aid for Scientific Research (B), Principal Investigator

     View Summary

    Interface dermatitis is a pathological feature which is commonly observed in a variety of skin diseases including lichen plans, severe drug adverse reaction, graft-versus-host disease, paraneoplastic pemphigus and so on. The molecular mechanism that leads to interface dermatitis has not been understood. In this project, we took advantage of genetically engineered mice and discovered that T-bet and Stat1, crucial transcriptional factors in T cell differentiation, are keys in development of interface dermatitis. On the other hand, we also sought to establish a novel concept in the field of Immunology in this project. Through investigating genes which are specifically induced by interleukin (IL)-27, we found that cholesterol metabolizing enzyme is induced by IL-27 and the function contributes to immune regulation. Our results are promisingly expected to be useful to invent a new treatment for skin inflammatory diseases in the future.

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Works 【 Display / hide

  • International League of Dermatological Societies-Newsletter「ILDS 2015 Young Dermatologist International Achievement Award(YDIAA) Winners」

    Hayato Takahashi

    2015.12

    Other

  • 慶應義塾医学部新聞「デスモグレイン3反応性T細胞による新規自己免疫性皮膚炎モデルの確立」

    高橋勇人

    2012.11

    Other

  • 慶應義塾医学部新聞「日本皮膚科学会 皆見省吾記念賞受賞」

    高橋勇人

    2012.07

    Other

Intellectual Property Rights, etc. 【 Display / hide

  • 自己免疫疾患における自己抗体産生を抑制するシグナル阻害自己免疫疾患治療剤

    Application No.: 特願2019-214253  2019.11 

    Joint

  • 25−ヒドロキシコレステロールを有効成分として含有してなる、活性化されたT細胞及び/又はB細胞に選択的な細胞死誘導剤又は細胞死促進剤

    Application No.: 特許出願2016-111556  2016.06 

    Patent, Joint, National application

Awards 【 Display / hide

  • Young Dermatologist International Achievement Award 2015

    2015.06, International League of Dermatological Societies

  • 三四会奨励賞受賞

    2012.11

     View Description

    第92回慶應医学会総会(於新棟11階大会議室)にて

  • 平成24年度皆見省吾記念賞

    2012.06

     View Description

    第111回日本皮膚科学会総会(於京都)にて

 

Courses Taught 【 Display / hide

  • LECTURE SERIES, DERMATOLOGY

    2021

  • LECTURE SERIES, DERMATOLOGY

    2020

  • LECTURE SERIES, DERMATOLOGY

    2019

Courses Previously Taught 【 Display / hide

  • 皮膚科学

    学校法人慶應義塾大学, 2018

  • 皮膚科学講義「皮膚の免疫・アレルギー・薬疹」2017/12/01

    Keio University, 2017

  • 皮膚科学講義「アレルギー性皮膚疾患・薬疹」2016/11/24

    Keio University, 2016

  • 皮膚科学講義「アレルギー性皮膚疾患・ 薬疹」2015/11/24

    Keio University, 2015

  • 皮膚科学講義「アレルギー性皮膚疾患・ 薬疹」2014/11/26

    Keio University, 2014

 

Memberships in Academic Societies 【 Display / hide

  • 日本炎症再生医学会, 

    2017
    -
    Present
  • 日本免疫学会, 

    2012
    -
    Present
  • 日本研究皮膚科学会, 

    2005
    -
    Present
  • 日本皮膚科学会, 

    2000
    -
    Present

Committee Experiences 【 Display / hide

  • 2017
    -
    Present

    日本研究皮膚科学会 ISID開設準備委員会 委員

  • 2017
    -
    2020

    日本研究皮膚科学会 推薦員会 委員

  • 2014
    -
    2017

    日本研究皮膚科学会 若手セミナー委員会 委員