論文 - 高橋　勇人

Guidelines for the Management of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis 2025 Supplement.

Watanabe H, Ogawa Y, Yamaguchi Y, Nakajima S, Mizukawa Y, Mushiroda T, Takahashi H, Fujiyama T, Sotozono C, Kaneko Y, Hasegawa A, Kobayashi K, Sunaga Y, Watanabe Y, Nomura T, Kabashima K, Inui A, Fujieda M, Ueta M, Hama N, Tohyama M, Abe R

The Journal of dermatology 53 （ 2 ） e88 - e101 2026年02月

査読有り,  ISSN  0385-2407

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Pemphigus: An Autoimmune Disease Model for Understanding the Role of Autoreactive T Cells.

Takahashi H

The Keio journal of medicine 74 （ 4 ） 177 - 188 2025年12月

単著, 筆頭著者, 最終著者, 責任著者, 査読有り,  ISSN  0022-9717

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Antigen-specific immune responses and microbiota interactions in skin: Insights into autoimmune skin diseases and emerging therapeutic strategies.

Takahashi H, Fukuda K, Ito Y, Amagai M

The Journal of allergy and clinical immunology 156 （ 3 ） 557 - 567 2025年09月

査読有り,  ISSN  0091-6749

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A case of epidermal growth factor receptor-mutant lung cancer with transformation from adenocarcinoma into small cell carcinoma suggested by histological investigation of skin metastasis.

Omasa H, Kakuta R, Terai H, Kawaida M, Hirai I, Tamura K, Ito Y, Fukushima-Nomura A, Amagai M, Takahashi H

The Journal of dermatology 52 （ 6 ） e538 - e540 2025年06月

査読有り,  ISSN  0385-2407

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Development of Japanese versions of the Autoimmune Bullous Disease Quality of Life and Treatment of Autoimmune Bullous Disease Quality of Life questionnaires.

Tanemura C, Nunotani M, Kawabata K, Morooka Y, Yamagami J, Kakuta R, Saito Y, Kurihara Y, Takahashi H, Ishii N, Koga H, Nakama T, Hayashi D, Hiroyasu S, Tateishi C, Tsuruta D, Murrell DF, Hashimoto T

The Journal of dermatology 52 （ 5 ） 812 - 830 2025年05月

査読有り,  ISSN  0385-2407

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Guidelines for the management of drug-induced hypersensitivity syndrome 2023.

Mizukawa Y, Hama N, Niihara H, Miyagawa F, Hashizume H, Tohyama M, Takahashi H, Watanabe H, Ohyama M, Yamaguchi Y, Kawamura T, Nomura T, Kabashima K, Sueki H, Morita E, Abe R, Asada H

The Journal of dermatology 52 （ 3 ） e189 - e209 2025年03月

査読有り,  ISSN  0385-2407

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Cutaneous Adverse Events Following COVID-19 Vaccination in Japan: A Questionnaire Survey.

Yamamura Y, Nakashima C, Kagawa N, Aoyama Y, Yamamoto A, Kawahira H, Kubota Y, Nakajima S, Nakahara T, Fuyuno Y, Tsuruta D, Matsumoto A, Matsuo R, Abe R, Yuki A, Takahashi H, Takahashi C, Imafuku S, Sato E, Fujiwara S, Yasuda M, Tada Y, Hayashi K, Katoh N, Watanabe D, Otsuka A

Cureus 17 （ 3 ） e80257 2025年03月

査読有り,  ISSN  2168-8184

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Sarcoid Vasculitis in the Skin: A Clinicopathologic Study of 8 Cases With Various Skin Lesions but the Common Unique Cannonball-like Vessel Destruction by Sarcoid Granulomas.

Chen KR, Miura K, Inazumi T, Nakamura Y, Nakajima H, Takahashi H, Yamamoto T

The American journal of surgical pathology 49 （ 2 ） 150 - 158 2025年02月

査読有り,  ISSN  0147-5185

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Autoimmune blistering diseases treated with glucocorticoids: An international study of steroid-induced myopathy.

He A, Koszegi B, Uzun S, Bilgic A, Bozca BC, Yang B, Daneshpazhooh M, Boziou M, Patsatsi A, Kakuta R, Takahashi H, Nery D, Mundin C, Ramirez-Quizon M, Culton D, McAlpine S, Johal J, Shulruf B, Stone JH, Murrell DF

Journal of the European Academy of Dermatology and Venereology : JEADV 39 （ 2 ） 340 - 349 2025年02月

査読有り,  ISSN  0926-9959

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Delayed and immediate cutaneous adverse events during pembrolizumab combination chemotherapy against cervical cancer: Case series.

Adachi T, Matsui T, Okata-Karigane U, Takahashi C, Tahara U, Hyodo M, Miyagawa A, Kobayashi K, Nakamura Y, Funakoshi T, Nishio H, Yamagami W, Takahashi H

The Journal of dermatology 52 （ 1 ） 132 - 137 2025年01月

査読有り,  ISSN  0385-2407

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Improvement of the Ocular Prognosis of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A National Survey in Japan.

Kojima M, Mieno H, Ueta M, Nakata M, Teramukai S, Sunaga Y, Ochiai H, Iijima M, Kokaze A, Watanabe H, Kurosawa M, Azukizawa H, Asada H, Watanabe Y, Yamaguchi Y, Aihara M, Ikezawa Z, Mizukawa Y, Ohyama M, Shiohara T, Hama N, Abe R, Hashizume H, Nakajima S, Nomura T, Kabashima K, Tohyama M, Hashimoto K, Takahashi H, Niihara H, Morita E, Sueki H, Kinoshita S, Sotozono C

American journal of ophthalmology 267   50 - 60 2024年11月

査読有り,  ISSN  0002-9394

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Acidic oral environment's potential contribution to palladium-induced systemic contact dermatitis: Case report.

Adachi T, Masaki K, Sujino K, Okata-Karigane U, Murakami T, Takahashi C, Nakayama S, Tomiyasu S, Asaoka M, Kabata H, Miyata J, Takahashi H, Fukunaga K

The journal of allergy and clinical immunology. Global 3 （ 4 ） 100333 2024年11月

査読有り

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Disruption of post-thymic tolerance in skin-reactive TCR transgenic mice through the interaction of lymphopenia and intestinal microbiota.

Hayabuchi H, Tokifuji Y, Takahashi H, Amagai M, Yoshimura A, Chikuma S

International immunology 36 （ 8 ） 413 - 424 2024年07月

査読有り,  ISSN  0953-8178

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Multiple subcutaneous abscesses by Corynebacterium amycolatum in a patient with severe idiopathic aplastic anaemia.

Shintani Y, Fukushima-Nomura A, Funakoshi T, Sakurai M, Kato J, Fukuyama M, Inazumi T, Ohkusu K, Takahashi H

Skin health and disease 4 （ 3 ） e351 2024年06月

査読有り

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A case of IgA pemphigus with acantholysis in oral mucosal lesions.

Yamanishi A, Ono N, Tsunoda A, Asahina Y, Fusumae T, Yamagami J, Sakai N, Ishii N, Amagai M, Takahashi H

Skin health and disease 4 （ 2 ） e327 2024年04月

査読有り

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Targeting abatacept-resistant T-helper-17 cells by aldehyde dehydrogenase inhibition.

Tokifuji Y, Hayabuchi H, Sasaki T, Hara-Chikuma M, Hirota K, Takahashi H, Amagai M, Yoshimura A, Chikuma S

iScience 27 （ 1 ） 108646 2024年01月

査読有り

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Attenuation of OX40 signaling suppression by age disrupts peripheral deletion of CD4⁺ T cells specific for the epidermal autoantigen desmoglein 3

Iriki H., Mukai M., Asahina Y., Kubo Y., Ito H., Amagai M., Takahashi H.

Immunity and Ageing （Immunity and Ageing）  20 （ 1 ） 26 2023年12月

査読有り,  ISSN  1742-4933

　概要を見る

Various autoimmune responses increase with age, but the underlying mechanism is not clear. In this study, we used CD4+ T cells expressing a transgenic T cell receptor specific for desmoglein 3 (Dsg3), which is the target antigen of the autoimmune bullous disease pemphigus vulgaris, to examine how peripheral immunological tolerance against pathogenic autoreactive CD4+ T cells changes with age. Dsg3-specific T cells were deleted within 14 days after adoptive transfer into young mice (8 weeks old), while they escaped deletion when transferred into older mice over 42 weeks old. Dsg3-specific T cells produced higher levels of the proinflammatory cytokine IFN-γ in aged mice than in young mice. In addition, the expression levels of both OX40 and Birc5, which are important for cell survival in T cell clonal proliferation, were higher in aged than in young mice. The dysfunction in suppressing proinflammatory cytokine secretion and Birc5 upregulation in Dsg3-specific autoreactive T cells may reflect an aspect of the preliminary steps in autoimmune disease development in the aged population. Understanding this mechanism may lead to better risk evaluation of autoimmune disease development and to onset prevention.

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Diverse Role of OX40 on T Cells as a Therapeutic Target for Skin Diseases

Iriki H., Takahashi H., Amagai M.

Journal of Investigative Dermatology （Journal of Investigative Dermatology）  143 （ 4 ） 545 - 553 2023年04月

ISSN  0022202X

　概要を見る

OX40 is an important costimulatory molecule for T-cell expansion and survival. Because OX40 is expressed on most T-cell subsets, it is an attractive therapeutic target for a variety of T-cell‒mediated diseases. Clinical trials are already underway for some skin inflammatory diseases. In this review, we present various observations that improve our understanding of how OX40-targeted therapy can be applied for skin inflammatory diseases, such as atopic dermatitis and psoriasis, T helper (Th)2- and Th17-mediated diseases, respectively. The important OX40/OX40L-mediated interaction between T cells and other immune cells is also discussed in terms of skin autoimmune diseases, such as alopecia areata and pemphigus. Regulatory T cells (Tregs) highly express OX40, and the skin harbors a large Treg population; thus, understanding how OX40-targeted treatment acts on Tregs is vital for the development of therapeutic strategies for various skin diseases.

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T cell autoimmunity and immune regulation to desmoglein 3, a pemphigus autoantigen

Takahashi H., Iriki H., Asahina Y.

Journal of Dermatology （Journal of Dermatology）  50 （ 2 ） 112 - 123 2023年02月

ISSN  03852407

　概要を見る

Pemphigus is a life-threatening autoimmune bullous disease mediated by anti-desmoglein IgG autoantibodies. Pemphigus is mainly classified into three subtypes: pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus. The pathogenicity of autoantibodies has been extensively studied. Anti-human CD20 antibody therapy targeting B cells emerged as a more effective treatment option compared to conventional therapy for patients with an intractable disease. On the other hand, autoreactive T cells are considered to be involved in the pathogenesis based on the test results of human leukocyte antigen association, autoreactive T cell detection, and cytokine profile analysis. Research on the role of T cells in pemphigus has continued to progress, including that on T follicular helper cells, which initiate molecular mechanisms involved in antibody production in B cells. Autoreactive T cell research in mice has highlighted the crucial roles of cellular autoimmunity and improved the understanding of its pathogenesis, especially in paraneoplastic pemphigus. The mouse research has helped elucidate novel regulatory mechanisms of autoreactive T cells, such as thymic tolerance to desmoglein 3 and the essential roles of regulatory T cells, Langerhans cells, and other molecules in peripheral tissues. This review focuses on the immunological aspects of autoreactive T cells in pemphigus by providing detailed information on various related topics.

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Rituximab therapy for intractable pemphigus: A multicenter, open-label, single-arm, prospective study of 20 Japanese patients

Yamagami J., Kurihara Y., Funakoshi T., Saito Y., Tanaka R., Takahashi H., Ujiie H., Iwata H., Hirai Y., Iwatsuki K., Ishii N., Sakurai J., Abe T., Takemura R., Mashino N., Abe M., Amagai M.

Journal of Dermatology （Journal of Dermatology）  50 （ 2 ） 175 - 182 2023年02月

ISSN  03852407

　概要を見る

This was a multicenter clinical trial of rituximab, a chimeric monoclonal IgG antibody directed against CD20, for the treatment of refractory pemphigus vulgaris and pemphigus foliaceus. In total, 20 patients were treated with two doses of rituximab (1000 mg; 2 weeks apart) on days 0 and 14. The primary end point was the proportion of patients who achieved complete or partial remission on day 168 following the first rituximab dose. Of the 20 enrolled patients, 11 (55%) and four (20%) achieved complete and partial remission, respectively; therefore, remission was achieved in a total of 15 patients (75.0% [95% confidence interval, 50.9%–91.3%]). It was demonstrated that the remission rate was greater than the prespecified threshold (5%). In addition, a significant improvement in clinical score (Pemphigus Disease Area Index) and decrease in serum anti-desmoglein antibody level were observed over time. Four serious adverse events (heart failure, pneumonia, radial fracture, and osteonecrosis) were recorded in two patients, of which only pneumonia was considered causally related with rituximab. The level of peripheral blood CD19-positive B lymphocytes was decreased on day 28 after rituximab treatment and remained low throughout the study period until day 168. Our results confirm the efficacy and safety of rituximab therapy for refractory pemphigus in Japanese patients.

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