Papers - Amagai, Masayuki

Azathioprine monotherapy in autoimmune blistering diseases: A feasible option for mild to moderate cases

Kakuta, R. Yamagami, J. Funakoshi, T. Takahashi, H. Ohyama, M. Amagai, M.

J Dermatol (Journal of Dermatology)  45 ( 3 ) 334 - 339 2018.03

Accepted,  ISSN  03852407

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© 2017 Japanese Dermatological Association Azathioprine (AZP) is used as a corticosteroid (CS)-sparing medication to treat autoimmune blistering diseases. In this study, we examined the efficacy of AZP and the feasibility of using AZP monotherapy (without CS) to treat pemphigus and pemphigoid. We performed a retrospective study of 10 Japanese patients (seven with pemphigus and three with pemphigoid) with mild to moderate disease activity who had been treated using AZP. The treatment efficacy was evaluated based on decreases in the disease activity scores and autoantibody titers. The results demonstrate that seven out of 10 cases (70%) were treated successfully using AZP monotherapy with no severe adverse effects. The disease activity scores of the successfully-treated patients decreased to zero after 1–37.5 months (average, 11.9) and the average disease activity scores in these cases decreased significantly at 2 months (38.2 ± 36.6%) compared with the scores of the three patients who required additional systemic CS therapy (77.5 ± 3.5%) (P < 0.05). Additionally, the autoantibody titers of five cases treated successfully using AZP decreased by half at 6 months. In conclusion, our findings suggest that AZP monotherapy is a viable treatment option for mild to moderate pemphigus and pemphigoid.

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A Life Full of Surprises and Excitement through Science in Dermatology

AMAGAI MASAYUKI

J Invest Dermatol 138 ( 3 ) 475 - 476 2018.03

Accepted

Case of lamotrigine-induced drug adverse reaction under tocilizumab treatment with clinical and virological features of drug-induced hypersensitivity syndrome

Iriki, H. Ouchi, T. Ito, H. Sawada, M. Mukai, M. Nomura, H. Baba, Y. Adachi, T. Funakoshi, T. Amagai, M. Takahashi, H.

J Dermatol (Journal of Dermatology)  45 ( 6 ) 738 - 741 2018.03

Accepted,  ISSN  03852407

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© 2018 Japanese Dermatological Association The pathological mechanisms and immunological kinetics of drug-induced hypersensitivity syndrome (DIHS), including the relevance of interleukin (IL)-6, remain unclear. We report a case of drug adverse reaction that does not fulfill the diagnostic criteria of DIHS but mimics its characteristic features. Because the patient was under anti-IL-6 therapy at the onset, some symptoms typically seen in DIHS were absent, such as fever and leukocyte count abnormalities. However, the characteristic features of DIHS were clearly observed in the subsequent course, including the repeated recurrence of skin rash, prolonged liver dysfunction and reactivation of herpes viruses. This case suggested that IL-6 role at the onset is not a main factor to determine the subsequent pathomechanism of DIHS and attention should be paid to the preceding therapy for achieving accurate diagnosis.

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タンポンの使用に起因したtoxic shock syndrome

AMAGAI MASAYUKI

皮膚病診療 40 ( 2 ) 193 - 196 2018.02

Research paper (scientific journal), Joint Work

Authors' reply: Paraneoplastic autoimmune multi-organ syndrome is a distinct entity from traditional pemphigus subtypes

Payne, A. S. Kasperkiewicz, M. Ellebrecht, C. T. Takahashi, H. Yamagami, J. Zillikens, D. Amagai, M.

Nat Rev Dis Primers 4   18013 2018.02

Accepted

Diagnosis and Management of Pemphigus: recommendations by an International Panel of Experts

Murrell, D. F. Pena, S. Joly, P. Marinovic, B. Hashimoto, T. Diaz, L. A. Sinha, A. A. Payne, A. S. Daneshpazhooh, M. Eming, R. Jonkman, M. F. Mimouni, D. Borradori, L. Kim, S. C. Yamagami, J. Lehman, J. S. Saleh, M. A. Culton, D. A. Czernik, A. Zone, J. J. Fivenson, D. Ujiie, H. Wozniak, K. Akman-Karakas, A. Bernard, P. Korman, N. J. Caux, F. Drenovska, K. Prost-Squarcioni, C. Vassileva, S. Feldman, R. J. Cardones, A. R. Bauer, J. Ioannides, D. Jedlickova, H. Palisson, F. Patsatsi, A. Uzun, S. Yayli, S. Zillikens, D. Amagai, M. Hertl, M. Schmidt, E. Aoki, V. Grando, S. A. Shimizu, H. Baum, S. Cianchini, G. Feliciani, C. Iranzo, P. Mascaro, J. M., Jr. Kowalewski, C. Hall, R. Groves, R. Harman, K. E. Marinkovich, M. P. Maverakis, E. Werth, V. P.

J Am Acad Dermatol e-pub ahead of print 2018.02

Accepted

重症感染症を転機に軽快した尋常性天疱瘡

AMAGAI MASAYUKI

皮膚病診療 40 ( 1 ) 15 - 18 2018.01

Research paper (scientific journal), Joint Work

Langerhans Cells Prevent Autoimmunity via Expansion of Keratinocyte Antigen-Specific Regulatory T Cells

Kitashima, D. Y. Kobayashi, T. Woodring, T. Idouchi, K. Doebel, T. Voisin, B. Adachi, T. Ouchi, T. Takahashi, H. Nishifuji, K. Kaplan, D. H. Clausen, B. E. Amagai, M. Nagao, K.

EBioMedicine (EBioMedicine)  27   293 - 303 2018.01

Accepted

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© 2017 Langerhans cells (LCs) are antigen-presenting cells in the epidermis whose roles in antigen-specific immune regulation remain incompletely understood. Desmoglein 3 (Dsg3) is a keratinocyte cell-cell adhesion molecule critical for epidermal integrity and an autoantigen in the autoimmune blistering disease pemphigus. Although antibody-mediated disease mechanisms in pemphigus are extensively characterized, the T cell aspect of this autoimmune disease still remains poorly understood. Herein, we utilized a mouse model of CD4+ T cell-mediated autoimmunity against Dsg3 to show that acquisition of Dsg3 and subsequent presentation to T cells by LCs depended on the C-type lectin langerin. The lack of LCs led to enhanced autoimmunity with impaired Dsg3-specific regulatory T cell expansion. LCs expressed the IL-2 receptor complex and the disruption of IL-2 signaling in LCs attenuated LC-mediated regulatory T cell expansion in vitro, demonstrating that direct IL-2 signaling shapes LC function. These data establish that LCs mediate peripheral tolerance against an epidermal autoantigen and point to langerin and IL-2 signaling pathways as attractive targets for achieving tolerogenic responses particularly in autoimmune blistering diseases such as pemphigus.

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Mechanisms Causing Loss of Keratinocyte Cohesion in Pemphigus

Spindler, V. Eming, R. Schmidt, E. Amagai, M. Grando, S. Jonkman, M. F. Kowalczyk, A. P. Muller, E. J. Payne, A. S. Pincelli, C. Sinha, A. A. Sprecher, E. Zillikens, D. Hertl, M. Waschke, J.

J Invest Dermatol (Journal of Investigative Dermatology)  138 ( 1 ) 32 - 37 2018.01

Accepted,  ISSN  0022202X

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© 2017 The Authors The autoimmune blistering skin disease pemphigus is caused by IgG autoantibodies against desmosomal cadherins, but the precise mechanisms are in part a matter of controversial discussions. This review focuses on the currently existing models of the disease and highlights the relevance of desmoglein-specific versus nondesmoglein autoantibodies, the contribution of nonautoantibody factors, and the mechanisms leading to cell dissociation and blister formation in response to autoantibody binding. As the review brings together the majority of laboratories currently working on pemphigus pathogenesis, it aims to serve as a solid basis for further investigations for the entire field.

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Combination of low-dose total skin electron beam therapy and subsequent localized skin electron beam therapy as a therapeutic option for advanced-stage mycosis fungoides

Kinoshita-Ise, M. Ouchi, T. Izumi, E. Kawaguchi, O. Nagao, K. Amagai, M. Funakoshi, T.

Clin Exp Dermatol e-pub ahead of print 2017.12

Accepted

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Association study of childhood food allergy with genome-wide association studies-discovered loci of atopic dermatitis and eosinophilic esophagitis

Hirota, T. Nakayama, T. Sato, S. Yanagida, N. Matsui, T. Sugiura, S. Takaoka, Y. Hizawa, N. Fujieda, S. Miyatake, A. Sasaki, T. Amagai, M. Doi, S. Ito, K. Ebisawa, M. Tamari, M.

J Allergy Clin Immunol 140 ( 6 ) 1713 - 1716 2017.12

Accepted

Bone Marrow-Derived Stem Cells Migrate into Intra-epidermal Skin Defects of a Desmoglein-3 knockout Mouse Model but Preserve their Mesodermal Differentiation

Hunefeld, C. Mezger, M. Muller-Hermelink, E. Schaller, M. Muller, I. Amagai, M. Handgretinger, R. Rocken, M.

J Invest Dermatol e-pub ahead of print 2017.12

Accepted

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E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning

Rubsam, M. Mertz, A. F. Kubo, A. Marg, S. Jungst, C. Goranci-Buzhala, G. Schauss, A. C. Horsley, V. Dufresne, E. R. Moser, M. Ziegler, W. Amagai, M. Wickstrom, S. A. Niessen, C. M.

Nat Commun 8 ( 1 ) 1250 2017.11

Accepted

Dermoscopy of pigmented invasive ductal carcinoma mimicking basal cell carcinoma

Horikawa, H. Umegaki-Arao, N. Funakoshi, T. Amagai, M. Tanaka, M.

Australas J Dermatol 58 ( 4 ) 326 - 327 2017.11

Accepted

Endoscopic findings of laryngopharyngeal and esophageal involvement in autoimmune bullous disease

Nakamura, R. Omori, T. Suda, K. Wada, N. Kawakubo, H. Takeuchi, H. Yamagami, J. Amagai, M. Kitagawa, Y.

Dig Endosc (Gastroenterological Endoscopy)  29 ( 7 ) 765 - 772 2017.11

Accepted,  ISSN  03871207

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© 2018 Japan Gastroenterological Endoscopy Society. All Rights Reserved. Background and Aim: Autoimmune bullous disease (ABD) is induced by autoantibodies against cell adhesion molecules, and blistering may occur on the mucous membranes of the eyes, nose, mouth, oral cavity, laryngopharynx, and esophagus. Endoscopic prevalence and features of ABD-associated esophageal lesions are not well known. We conducted the present study to assess the endoscopic prevalence of ABD-associated mucosal lesions. Methods: Endoscopic prevalence of mucosal lesions, particularly laryngopharyngeal and esophageal lesions, was used as the primary endpoint to assess the significance of upper gastrointestinal endoscopy, and clinical and endoscopic features were secondary endpoints. Results: Of 123 ABD patients, 50.4％ had apparent oral or laryngopharyngeal lesions and 30.8％had laryngopharyngeal lesions. Esophageal lesions were detected through normal observation in 16.8％ of affected patients, whereas 40.6％ exhibited epidermolysis or blood blisters by mechanical inducement, regardless of esophageal mucosal lesion detection by normal observation. Additionally, 56.0％ exhibited the Nikolsky sign with mechanical inducement. Of the 123 patients, 29.2％ did not have exposed skin lesions. Of these patients, 77.7％ had oral cavity or laryngopharyngeal lesions, 36.1％ had esophageal lesions, and 58.3％ exhibited the Nikolsky sign on esophageal mucosa. Conclusion: It is important to determine the endoscopic characteristics and findings of ABD. ABD can be suspected from endoscopic findings.

インフリキシマブ投与開始後に自己免疫性肝炎を発症した尋常性乾癬の1例

AMAGAI MASAYUKI

皮膚科の臨床 59 ( 11 ) 1721 - 1724 2017.10

Research paper (scientific journal), Joint Work

悪性黒色腫に対する腫瘍浸潤リンパ球(TIL)輸注療法のfeasibility試験

AMAGAI MASAYUKI

Skin Cancer 32 ( 2 ) 143 - 147 2017.10

Research paper (scientific journal), Joint Work

水疱症の新しい治療

AMAGAI MASAYUKI

皮膚科の臨床 59 ( 11 ) 1621 - 1628 2017.10

Research paper (scientific journal), Joint Work

Inflammation-free, gas-permeable, lightweight, stretchable on-skin electronics with nanomeshes

Miyamoto, Akihito, Lee, Sungwon, Cooray, Nawalage Florence, Lee, Sunghoon, Mori, Mami, Matsuhisa, Naoji, Jin, Hnbit, Yoda, Leona, Yokota, Tomoyuki, Itoh, Akira, Sekino, Masaki, Kawasaki, Hiroshi, Ebihara, Tamotsu, Amagai, Masayuki, Someya, Takao

NATURE NANOTECHNOLOGY 12 ( 9 ) 907 - + 2017.09

Research paper (scientific journal),  ISSN  1748-3387

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Case of primary cutaneous methotrexate-associated Hodgkin's lymphoma

Baba, Yuko, Tanese, Keiji, Amagai, Masayuki, Kameyama, Kaori, Saito, Masataka

JOURNAL OF DERMATOLOGY 44 ( 9 ) 1079 - 1081 2017.09

Research paper (scientific journal),  ISSN  0385-2407