Updated on 2024/11/21

Information

 

写真a

 
watanabe mitsuru
 
Organization
Kyushu University Hospital Neurology Assistant Professor
School of Medicine Department of Medicine（Concurrent）
Title
Assistant Professor
Tel
0926425340
Profile
神経内科一般、特に多発性硬化症や視神経脊髄炎スペクトラム障害・重症筋無力症を中心とした神経免疫疾患患者の診療を主に行っている。 研究に関しても、多発性硬化症や視神経脊髄炎スペクトラム障害患者を対象とした疫学調査に加え、血清・髄液中のバイオマーカー探索やフローサイトメトリーを用いた免疫細胞の解析を行っている。 また医学生の実習の指導、大学院生の研究の指導など教育にも携わっている。
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Degree

  • MD, PhD (Kyushu University)

Research Interests・Research Keywords

  • Research theme：Epidemiologic studies of Japanese multiple sclerosis and neuromyelitis optica spectrum disorder

    Keyword：multiple sclerosis, neuromyelitis optica spectrum disorder, Japanese, HLA

    Research period： 2017.4

  • Research theme：Immunology and biomarker in multiple sclerosis and neuromyelitis optica spectrum disorder

    Keyword：multiple sclerosis, neuromyelitis optica spectrum disorder

    Research period： 2017.4

  • Research theme：Regulatory mechanisms of Connexins on astrocytes in multiple sclerosis

    Keyword：multiple sclerosis, astrocyte, connexin

    Research period： 2012.4 - 2017.3

Awards

  • 日本神経免疫学会研究創世賞　優秀賞

    2022.10   日本神経免疫学会   多発性硬化症におけるγδ型T細胞の病態関与と治療反応性バイオマーカーとしての有用性の検討

  • MSVirtual2020 Educational Grant

    2020.9   8th Joint ACTRIMS-ECTRIMS Meeting  

  • 優秀演題賞

    2018.11   日本神経治療学会学術集会  

  • Investigator Award（最優秀口演賞）

    2018.11  

  • 最優秀口演賞（基礎・臨床研究部門）

    2018.10   日本神経感染症学会総会・学術大会  

  • 学長賞（最優秀賞）

    2018.8  

  • Travel Award

    2016.9   European Committee for Treatment and Research in Multiple Sclerosis  

  • 学術委員会委員長賞

    2016.8  

  • Travel Award

    2015.10   European Committee for Treatment and Research in Multiple Sclerosis  

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Papers

  • HLA genotype-clinical phenotype correlations in multiple sclerosis and neuromyelitis optica spectrum disorders based on Japan MS/NMOSD Biobank data. Reviewed International journal

    Watanabe M, Nakamura Y, Sato S, Niino M, Fukaura H, Tanaka M, Ochi H, Kanda T, Takeshita Y, Yokota T, Nishida Y, Matsui M, Nagayama S, Kusunoki S, Miyamoto K, Mizuno M, Kawachi I, Saji E, Ohashi T, Shimohama S, Hisahara S, Nishiyama K, Iizuka T, Nakatsuji Y, Okuno T, Ochi K, Suzumura A, Yamamoto K, Kawano Y, Tsuji S, Hirata M, Sakate R, Kimura T, Shimizu Y, Nagaishi A, Okada K, Hayashi F, Sakoda A, Masaki K, Shinoda K, Isobe N, Matsushita T, Kira J.

    Scientific Reports   11 ( 1 )   607 - 607   2021.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41598-020-79833-7

  • Serum GFAP and neurofilament light as biomarkers of disease activity and disability in NMOSD Reviewed International journal

    Mitsuru Watanabe, Yuri Nakamura, Zuzanna Michalak, Noriko Isobe, Christian Barro, David Leppert, Takuya Matsushita, Fumie Hayashi, Ryo Yamasaki, Jens Kuhle, Jun Ichi Kira

    Neurology   93 ( 13 )   E1299 - E1311   2019.9

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1212/WNL.0000000000008160

  • Oral phase dysphagia in facial onset sensory and motor neuronopathy Reviewed International journal

    Mitsuru Watanabe, Wataru Shiraishi, Ryo Yamasaki, Noriko Isobe, Motohiro Sawatsubashi, Ryuji Yasumatsu, Takashi Nakagawa, Jun-ichi Kira

    Brain and Behavior   8 ( 6 )   2018.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1002/brb3.999

  • Th1 cells downregulate connexin 43 gap junctions in astrocytes via microglial activation Reviewed International journal

    Mitsuru Watanabe, Katsuhisa Masaki, Ryo Yamasaki, Jun Kawanokuchi, Hideyuki Takeuchi, Takuya Matsushita, Akio Suzumura, Jun-ichi Kira

    Scientific Reports   6   2016.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/srep38387

  • Antibodies to neural and non-neural autoantigens in Japanese patients with CNS demyelinating disorders Reviewed International journal

    Mitsuru Watanabe, Takayuki Kondo, Kenji Murakata, Takashi Kageyama, Yoko Shibata, Toshiyuki Takahashi, Kyoichi Nomura, Sadayuki Matsumoto

    Journal of Neuroimmunology   274 ( 1-2 )   155 - 160   2014.1

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    DOI： 10.1016/j.jneuroim.2014.06.020

  • Prevalence of, and Disability Due to, Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder in Japan by the Fifth Nationwide Survey

    Watanabe M., Isobe N., Niino M., Nakashima I., Matsushita T., Sakai Y., Nakahara J., Kawachi I., Ochi H., Nakatsuji Y., Nakamura Y., Nakamura K., Sakata K., Matsui M., Kuwabara S., Kira J.I.

    Neurology   103 ( 10 )   e209992   2024.11   （ ISSN:0028-3878 ）

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    Language：English   Publisher：Neurology  

    BACKGROUND AND OBJECTIVES: All 4 previous nationwide surveys of multiple sclerosis (MS) in Japan were conducted before the discovery of anti-aquaporin-4 (AQP4) antibodies; thus, neuromyelitis optica spectrum disorder (NMOSD) was included in MS, as optic-spinal MS. We aimed to clarify the epidemiologic features and trends of MS and NMOSD in Japan separately using a fifth nationwide survey. METHODS: The primary survey, in which a questionnaire was sent to 3,799 selected departments (including neurology/internal medicine, pediatrics, and ophthalmology), explored the estimated number and prevalence of patients with MS or NMOSD in 2017, and the secondary survey collected detailed characteristics of the patients using a second questionnaire. RESULTS: The response rates for the primary and secondary surveys were 60.1% and 53.9%, respectively. The estimated total number of patients with MS or NMOSD was 24,800, 2.5-fold higher than that in the fourth survey in 2003. The crude prevalence was 19.6 per 100,000 patients (14.2 for MS and 5.4 for NMOSD), compared with 7.7 per 100,000 patients in the fourth survey. Patients with MS showed milder disability (median Expanded Disability Status Scale [EDSS] score: 2.0 [interquartile range 1.0-4.5] vs 2.5 [1.0-6.0]), decreased secondary progression (8.5% vs 15.2%), and increased usage of disease-modifying drugs (63.7% vs 37.2%) compared with those with conventional MS in the fourth survey. The proportions of oligoclonal bands and Barkhof criteria fulfillment on MRI, which are features of classical MS, increased with advancing year of birth. Patients with NMOSD also showed less disability and shorter disease duration than patients with optic-spinal MS in the fourth survey (EDSS score: 3.5 [2.0-5.5] vs 3.8 [2.0-6.0]; disease duration: 8.0 [3.9-14.8] vs 10.0 [5.0-16.0]). Among patients with NMOSD, disability was exacerbated by a history of longitudinally extensive spinal cord lesions and anti-AQP4 antibody positivity, which both decreased with advancing year of birth. DISCUSSION: The prevalences of MS (particularly with classical features) and NMOSD have been increasing in Japan, suggesting the contribution of environmental factors. However, disabilities in patients with MS and NMOSD have been mitigated. Extensive usage of various disease-modifying drugs could be a factor contributing to this disability mitigation in MS.

    DOI： 10.1212/WNL.0000000000209992

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  • The Efficacy of Eculizumab in the Acute Phase of Neuromyelitis Optica Spectrum Disorder: A Case Series Study.

    Watanabe M, Masaki K, Tanaka E, Matsushita T, Isobe N

    Cureus   16 ( 11 )   e73205   2024.11   （ ISSN:2168-8184 ）

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    DOI： 10.7759/cureus.73205

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  • Clinical practice guidelines for multiple sclerosis, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease 2023 in Japan

    Niino, M; Isobe, N; Araki, M; Ohashi, T; Okamoto, T; Ogino, M; Okuno, T; Ochi, H; Kawachi, I; Shimizu, Y; Takahashi, K; Takeuchi, H; Tahara, M; Chihara, N; Nakashima, I; Fukaura, H; Misu, T; Miyazaki, Y; Miyamoto, K; Mori, M; Kinoshita, M; Takai, Y; Fujii, C; Watanabe, M; Fujihara, K

    MULTIPLE SCLEROSIS AND RELATED DISORDERS   90   105829   2024.10   （ ISSN:2211-0348 eISSN:2211-0356 ）

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    Language：English   Publisher：Multiple Sclerosis and Related Disorders  

    Background: The previous Japanese clinical practice guidelines for multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) were published in 2017. Recently, for the first time in 6 years, the MS and NMOSD guideline development committee revised the Japanese guidelines for MS, NMOSD, and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Methods: The committee utilized the Grading of Recommendations Assessment, Development, and Evaluation system based on the “Minds Handbook for Clinical Practice Guideline Development 2020 Ver. 3.0″ with a focus on clinical questions (CQs). The committee also discussed clinical issues other than CQs, categorizing them as a question-and-answer (Q&A) section, including “issues on which experts’ opinions agree to a certain extent” and “issues that are important but not included in the CQ”. Results: The committee identified 3, 1, and 1 key CQs related to MS, NMOSD, and MOGAD, respectively, and presented recommendations. A Q&A session regarding disease-modifying therapies and relapse prevention therapies for MS, NMOSD, and MOGAD was conducted. The revised guidelines were published in September 2023. Conclusions: The Japanese guidelines for clinical practice on MS, NMOSD, and MOGAD were updated. Treatment strategies for MS, NMOSD, and MOGAD are changing, and these updated guidelines may assist with treatment decisions for these diseases in clinical practice.

    DOI： 10.1016/j.msard.2024.105829

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  • Three-dimensional magnetic resonance imaging of Baló-like concentric lesion in multiple sclerosis

    Iwao, K; Masaki, K; Tanaka, E; Watanabe, M; Kira, Y; Shinoda, K; Matsushita, T; Araki, S; Togao, O; Isobe, N

    NEUROLOGY AND CLINICAL NEUROSCIENCE   2024.8   （ ISSN:2049-4173 ）

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    Publisher：Neurology and Clinical Neuroscience  

    DOI： 10.1111/ncn3.12852

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  • Distinct retinal reflectance spectra from retinal hyperspectral imaging in Parkinson's disease

    Ueda, E; Watanabe, M; Nakamura, D; Matsuse, D; Tanaka, E; Fujiwara, K; Hashimoto, S; Nakamura, S; Isobe, N; Sonoda, KH

    JOURNAL OF THE NEUROLOGICAL SCIENCES   461   123061   2024.6   （ ISSN:0022-510X eISSN:1878-5883 ）

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    Language：English   Publisher：Journal of the Neurological Sciences  

    Background: Recent developments in the retinal hyperspectral imaging method have indicated its potential in addressing challenges posed by neurodegenerative disorders, such as Alzheimer's disease. This human clinical study is the first to assess reflectance spectra obtained from this imaging as a tool for diagnosing patients with Parkinson's disease (PD). Methods: Retinal hyperspectral imaging was conducted on a total of 40 participants, including 20 patients with PD and 20 controls. Following preprocessing, retinal reflectance spectra were computed for the macular retina defined by four rectangular regions. Linear discriminant analysis classifiers underwent training to discern patients with PD from control participants. To assess the performance of the selected features, nested leave-one-out cross-validation was employed using machine learning. The indicated values include the area under the curve (AUC) and the corresponding 95% confidence interval (CI). Results: Retinal reflectance spectra of PD patients exhibited variations in the spectral regions, particularly at shorter wavelengths (superonasal retina, wavelength < 490 nm; inferonasal retina, wavelength < 510 nm) when compared to those of controls. Retinal reflectance spectra yielded an AUC of 0.60 (95% CI: 0.43–0.78) and 0.60 (95% CI: 0.43–0.78) for the superonasal and inferonasal retina, respectively, distinguishing individuals with and without PD. Conclusion: Reflectance spectra obtained from retinal hyperspectral imaging tended to decrease at shorter wavelengths across a broad spectral range in PD patients. Further investigations building upon these preliminary findings are imperative to focus on the retinal spectral signatures associated with PD pathological hallmarks, including α-synuclein.

    DOI： 10.1016/j.jns.2024.123061

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  • Astroglial connexin 43 is a novel therapeutic target for chronic multiple sclerosis model

    Takase, EO; Yamasaki, R; Nagata, S; Watanabe, M; Masaki, K; Yamaguchi, H; Kira, J; Takeuchi, H; Isobe, N

    SCIENTIFIC REPORTS   14 ( 1 )   10877   2024.5   （ ISSN:2045-2322 ）

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    Language：English   Publisher：Scientific Reports  

    In chronic stages of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalitis (EAE), connexin (Cx)43 gap junction channel proteins are overexpressed because of astrogliosis. To elucidate the role of increased Cx43, the central nervous system (CNS)-permeable Cx blocker INI-0602 was therapeutically administered. C57BL6 mice with chronic EAE initiated by MOG35-55 received INI-0602 (40 mg/kg) or saline intraperitoneally every other day from days post-immunization (dpi) 17–50. Primary astroglia were employed to observe calcein efflux responses. In INI-0602-treated mice, EAE clinical signs improved significantly in the chronic phase, with reduced demyelination and decreased CD3+ T cells, Iba-1+ and F4/80+ microglia/macrophages, and C3+GFAP+ reactive astroglia infiltration in spinal cord lesions. Flow cytometry analysis of CD4+ T cells from CNS tissues revealed significantly reduced Th17 and Th17/Th1 cells (dpi 24) and Th1 cells (dpi 50). Multiplex array of cerebrospinal fluid showed significantly suppressed IL-6 and significantly increased IL-10 on dpi 24 in INI-0602-treated mice, and significantly suppressed IFN-γ and MCP-1 on dpi 50 in the same group. In vitro INI-0602 treatment inhibited ATP-induced calcium propagations of Cx43+/+ astroglial cells to similar levels of those of Cx43−/− cells. Astroglial Cx43 hemichannels represent a novel therapeutic target for chronic EAE and MS.

    DOI： 10.1038/s41598-024-61508-2

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  • A nationwide survey of facial onset sensory and motor neuronopathy in Japan. Reviewed International journal

    Ko S, Yamasaki R, Okui T, Shiraishi W, Watanabe M, Hashimoto Y, Kobayakawa Y, Kusunoki S, Kira JI, Isobe N.

    J Neurol Sci   459   122957   2024.3   （ ISSN:0022-510X eISSN:1878-5883 ）

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.jns.2024.122957

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  • Case series of eculizumab treatment on NMOSD attacks

    Watanabe, M; Masaki, K; Tanaka, E; Matsushita, T; Isobe, N

    MULTIPLE SCLEROSIS JOURNAL   29   947 - 948   2023.10   （ ISSN:1352-4585 eISSN:1477-0970 ）

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  • Iguratimod Ameliorates the Severity of Secondary Progressive Multiple Sclerosis in Model Mice by Directly Inhibiting IL-6 Production and Th17 Cell Migration via Mitigation of Glial Inflammation. Reviewed International journal

    Nagata S, Yamasaki R, Takase EO, Iida K, Watanabe M, Masaki K, Wijering MHC, Yamaguchi H, Kira J, Isobe N.

    Biology (Basel). 2023;12(9):1217.   12 ( 9 )   1217   2023.9

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.3390/biology12091217.

  • Iguratimod Ameliorates the Severity of Secondary Progressive Multiple Sclerosis in Model Mice by Directly Inhibiting IL-6 Production and Th17 Cell Migration via Mitigation of Glial Inflammation

    Nagata, S; Yamasaki, R; Takase, EO; Iida, K; Watanabe, M; Masaki, K; Wijering, MHC; Yamaguchi, H; Kira, J; Isobe, N

    BIOLOGY-BASEL   12 ( 9 )   2023.9   （ ISSN:2079-7737 eISSN:2079-7737 ）

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    Language：English   Publisher：Biology  

    We previously reported a novel secondary progressive multiple sclerosis (SPMS) model, progressive experimental autoimmune encephalomyelitis (pEAE), in oligodendroglia-specific Cx47-inducible conditional knockout (Cx47 icKO) mice. Based on our prior study showing the efficacy of iguratimod (IGU), an antirheumatic drug, for acute EAE treatment, we aimed to elucidate the effect of IGU on the SPMS animal model. We induced pEAE by immunizing Cx47 icKO mice with myelin oligodendrocyte glycoprotein peptide 35–55. IGU was orally administered from 17 to 50 days post-immunization. We also prepared a primary mixed glial cell culture and measured cytokine levels in the culture supernatant after stimulation with designated cytokines (IL-1α, C1q, TNF-α) and lipopolysaccharide. A migration assay was performed to evaluate the effect of IGU on the migration ability of T cells toward mixed glial cell cultures. IGU treatment ameliorated the clinical signs of pEAE, decreased the demyelinated area, and attenuated glial inflammation on immunohistochemical analysis. Additionally, IGU decreased the intrathecal IL-6 level and infiltrating Th17 cells. The migration assay revealed reduced Th17 cell migration and IL-6 levels in the culture supernatant after IGU treatment. Collectively, IGU successfully mitigated the clinical signs of pEAE by suppressing Th17 migration through inhibition of IL-6 production by proinflammatory-activated glial cells.

    DOI： 10.3390/biology12091217

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  • Exosome Connexin43-Truncated Isoforms and Bound RNAs Distinctively Associated with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

    Kira, JI; Maimaitijiang, G; Sakoda, A; Masaki, K; Watanabe, M; Nagata, S; Ozdemir, E; Yamasaki, R; Isobe, N; Zhang, X; Imamura, T; Nakamura, Y

    ANNALS OF NEUROLOGY   94   S54 - S55   2023.9   （ ISSN:0364-5134 eISSN:1531-8249 ）

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  • Real-world experience with eculizumab in Japanese patients with myasthenia gravis: Post-marketing surveillance data

    Takahashi, M; Masuda, M; Watanabe, M; Fukamizu, Y; Osawa, T; Kikui, H; Murai, H

    EUROPEAN JOURNAL OF NEUROLOGY   30   574 - 574   2023.6   （ ISSN:1351-5101 eISSN:1468-1331 ）

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  • Factors Associated with Glatiramer Acetate Efficacy in Japanese Multiple Sclerosis

    Tanaka, E; Watanabe, M; Fukumoto, S; Suezumi, K; Matsushita, T; Isobe, N; Masaki, K

    MULTIPLE SCLEROSIS JOURNAL   29 ( 7 )   NP34 - NP35   2023.6   （ ISSN:1352-4585 eISSN:1477-0970 ）

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  • Astroglial Connexin 43 is a Novel Therapeutic Target for a Chronic Multiple Sclerosis Model

    Ozdemir, E; Yamasaki, R; Nagata, S; Watanabe, M; Yamaguchi, H; Masaki, K; Kira, J; Takeuchi, H; Isobe, N

    MULTIPLE SCLEROSIS JOURNAL   29 ( 7 )   NP2 - NP2   2023.6   （ ISSN:1352-4585 eISSN:1477-0970 ）

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  • Early and extensive alterations of glial connexins, distal oligodendrogliopathy type demyelination, and nodal/paranodal pathology are characteristic of multiple system atrophy Invited Reviewed International journal

    Nishimura, Yuji; Masaki, Katsuhisa; Matsuse, Dai; Yamaguchi, Hiroo; Tanaka, Tatsunori; Matsuo, Eriko; Hayashida, Shotaro; Watanabe, Mitsuru; Matsushita, Takuya; Sadashima, Shoko; Sasagasako, Naokazu; Yamasaki, Ryo; Isobe, Noriko; Iwaki, Toru; Kira, Jun-Ichi

    BRAIN PATHOLOGY   33 ( 3 )   e13131   2023.5   （ ISSN:1015-6305 eISSN:1750-3639 ）

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1111/bpa.13131

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  • Granulocyte activation markers in cerebrospinal fluid differentiate acute neuromyelitis spectrum disorder from multiple sclerosis Reviewed International journal

    Leppert, David; Watanabe, Mitsuru; Schaedelin, Sabine; Piehl, Fredrik; Furlan, Roberto; Gastaldi, Matteo; Lambert, Jeremy; Evertsson, Bjorn; Fink, Katharina; Matsushita, Takuya; Masaki, Katsuhisa; Isobe, Noriko; Kira, Jun-ichi; Benkert, Pascal; Maceski, Aleksandra; Willemse, Eline; Oechtering, Johanna; Orleth, Annette; Meier, Stephanie; Kuhle, Jens

    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY   94 ( 9 )   726 - 737   2023.4   （ ISSN:0022-3050 eISSN:1468-330X ）

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1136/jnnp-2022-330796

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  • Long-lasting pain and somatosensory disturbances in children with myelin oligodendrocyte glycoprotein antibody-associated disease Invited Reviewed International journal

    Ichimiya, Yuko; Chong, Pin Fee; Sonoda, Yuri; Tocan, Vlad; Watanabe, Mitsuru; Torisu, Hiroyuki; Kira, Ryutaro; Takahashi, Toshiyuki; Kira, Jun-Ichi; Isobe, Noriko; Sakai, Yasunari; Ohga, Shouichi

    EUROPEAN JOURNAL OF PEDIATRICS   182 ( 7 )   3175 - 3185   2023.4   （ ISSN:0340-6199 eISSN:1432-1076 ）

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1007/s00431-023-04989-z

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  • Effect of smoking on disease activity in multiple sclerosis patients treated with dimethyl fumarate or fingolimod Invited Reviewed International journal

    Tanaka, Eizo; Watanabe, Mitsuru; Fukumoto, Shoko; Masaki, Katsuhisa; Yamasaki, Ryo; Matsushita, Takuya; Isobe, Noriko

    MULTIPLE SCLEROSIS AND RELATED DISORDERS   70   104513   2023.2   （ ISSN:2211-0348 eISSN:2211-0356 ）

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.msard.2023.104513

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  • A case report of anti-N-methyl-D-aspartate receptor encephalitis with chromosomally integrated human herpesvirus 6

    Iwao, K; Watanabe, M; Mukaino, T; Fujii, T; Yamasaki, R; Isobe, N

    NEUROLOGY AND CLINICAL NEUROSCIENCE   11 ( 1 )   52 - 54   2023.1   （ ISSN:2049-4173 ）

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    Publisher：Neurology and Clinical Neuroscience  

    Chromosomally integrated human herpesvirus 6 (ciHHV6) is a condition where HHV6-DNA is integrated into the host germline genome. ciHHV6 can be misdiagnosed as active HHV6 infection. We report a 30-year-old woman presenting with psychological symptoms without a history of immunodeficiency. She had an ovarian teratoma and anti-N-methyl-D-aspartate receptor (NMDAR) antibodies in the cerebrospinal fluid (CSF) with HHV6-DNA in the serum and CSF. The final diagnosis was anti-NMDAR encephalitis and ciHHV6 because laparoscopic oophorectomy and immunotherapy ameliorated her symptoms and HHV6-DNA was detected in her oral mucosa cells. This case suggests the need to assess whether HHV6-DNA is related to infection or ciHHV6 when HHV6-DNA is detected in the CSF of patients with encephalitis.

    DOI： 10.1111/ncn3.12681

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  • 染色体に組み込まれたヒトヘルペスウイルス6を伴う抗NMDA受容体脳炎の症例報告(A case report of anti-N-methyl-D-aspartate receptor encephalitis with chromosomally integrated human herpesvirus 6)

    Iwao Kazunori, Watanabe Mitsuru, Mukaino Takahiko, Fujii Takayuki, Yamasaki Ryo, Isobe Noriko

    Neurology and Clinical Neuroscience   11 ( 1 )   52 - 54   2023.1

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    Language：English   Publisher：(一社)日本神経学会  

    脳脊髄液(CSF)で抗NMDA受容体(NMDAR)抗体とヒトヘルペスウイルス6(HHV6)-DNA陽性を示し、抗NMDAR脳炎および染色体に組み込まれたHHV6(ciHHV6)と最終診断された1例について報告した。症例は30歳女性で、Day0に亜急性の情動不安と錯乱状態を呈し頭痛を伴い、Day39に自宅の二階から飛び降りた。救急搬送されたが妄想が認められたため精神病院に移送され、移送先の医療施設で自己免疫性脳炎が疑われたことから、Day67に見当識障害、幻視、被害妄想、妄想気分、情緒不安定、激越を伴った状態で当院に移送された。CSFには軽度の髄液細胞増加、高タンパク血症、抗NMDAR抗体が検出され、血清とCSFからはHHV6-DNA陽性が示されたが、他のヘルペスウイルスDNAは陰性であった。脳波では突発活動を伴わないdiffuse background slowingが検出され、脳MRI検査では正常所見であったが、HHV6脳炎と抗NMDAR脳炎を疑い、抗ウイルス薬投与とメチルプレドニゾロン静注後に、静注免疫グロブリンが投与された。Day82に左卵巣腫瘍に対し腹腔鏡下卵巣摘出術を行い、血漿交換を行ったところ症状は改善され、CSF中細胞数とタンパク質も正常値に低下し、脳波も正常化した。しかし、6週間のガンシクロビル投与後も血清/CSFともにHHV6-DNA陽性、口腔粘膜細胞もHHV6-DNA陽性で、ガンシクロビル投与を中止したが、症状の増悪はみられなかった。以上の所見から、本例は抗NMDAR脳炎とciHHV6と最終診断された。

  • A case report of anti-N-methyl-d-aspartate receptor encephalitis with chromosomally integrated human herpesvirus 6

    Iwao Kazunori, Watanabe Mitsuru, Mukaino Takahiko, Fujii Takayuki, Yamasaki Ryo, Isobe Noriko

    Neurology and Clinical Neuroscience   11 ( 1 )   52 - 54   2022.10   （ ISSN:20494173 ）

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    Language：English  

    Chromosomally integrated human herpesvirus 6 (ciHHV6) is a condition where HHV6- DNA is integrated into the host germline genome. ciHHV6 can be misdiagnosed as active HHV6 infection. We report a 30-year-old woman presenting with psychological symptoms without a history of immunodeficiency. She had an ovarian teratoma and anti-N-methyl-D-aspartate receptor (NMDAR) antibodies in the cerebrospinal fluid (CSF) with HHV6-DNA in the serum and CSF. The final diagnosis was anti-NMDAR encephalitis and ciHHV6 because laparoscopic oophorectomy and immunotherapy ameliorated her symptoms and HHV6-DNA was detected in her oral mucosa cells. This case suggests the need to assess whether HHV6-DNA is related to infection or ciHHV6 when HHV6-DNA is detected in the CSF of patients with encephalitis.

    CiNii Research

  • Choroid Plexus Volume in Multiple Sclerosis versus Neuromyelitis Optica Spectrum Disorder: a retrospective, cross-sectional analysis. Reviewed International journal

    Neurol Neuroimmunol Neuroinflamm   9 ( 3 )   e1147   2022.2   （ ISSN:2332-7812 ）

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1212/NXI.0000000000001147

    Web of Science

    Scopus

    PubMed

  • A new clustering method identifies multiple sclerosis‐specific T‐cell receptors Reviewed International journal

    8 ( 1 )   163 - 176   2021.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1002/acn3.51264

  • Genetic factors for susceptibility to and manifestations of neuromyelitis optica Reviewed International journal

    Matsushita T, Masaki K, Isobe N, Sato S, Yamamoto K, Nakamura Y, Watanabe M, Suenaga T, Kira J

    Ann Clin Transl Neurol.   7 ( 22 )   2082 - 2093   2020.11

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    Language：English   Publishing type：Research paper (scientific journal)  

  • Distinct microglial and macrophage distribution patterns in the concentric and lamellar lesions in Baló's disease and neuromyelitis optica spectrum disorders. Reviewed International journal

    30 ( 6 )   1144 - 1157   2020.11

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1111/bpa.12898

  • Two susceptible HLA-DRB1 alleles for multiple sclerosis differentially regulate anti-JC virus antibody serostatus along with fingolimod Reviewed International journal

    Mitsuru Watanabe, Yuri Nakamura, Noriko Isobe, Masami Tanaka, Ayako Sakoda, Fumie Hayashi, Yuji Kawano, Ryo Yamasaki, Takuya Matsushita, Jun Ichi Kira

    Journal of neuroinflammation   17 ( 1 )   206   2020.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1186/s12974-020-01865-7

  • Risk HLA-DRB1 alleles differentially influence brain and lesion volumes in Japanese patients with multiple sclerosis Reviewed

    Shoko Fukumoto, Yuri Nakamura, Mitsuru Watanabe, Noriko Isobe, Takuya Matsushita, Ayako Sakoda, Akio Hiwatashi, Koji Shinoda, Ryo Yamasaki, Akira Tsujino, Jun ichi Kira

    Journal of the Neurological Sciences   413   2020.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.jns.2020.116768

  • An autopsied case of severe varicella zoster virus-associated encephalomyelitis under immunosuppressant therapy Reviewed

    Yasuhiro Maeda, Mitsuru Watanabe, Norihisa Maeda, Hidenori Ogata, Koji Shinoda, Toru Iwaki, Jun Ichi Kira

    Clinical Neurology   60 ( 5 )   351 - 357   2020.5

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    Language：Japanese   Publishing type：Research paper (scientific journal)  

    DOI： 10.5692/clinicalneurol.cn-001413

  • Environmental risk factors for multiple sclerosis in Japanese people Reviewed

    Ayako Sakoda, Takuya Matsushita, Yuri Nakamura, Mitsuru Watanabe, Koji Shinoda, Katsuhisa Masaki, Noriko Isobe, Ryo Yamasaki, Jun ichi Kira

    Multiple Sclerosis and Related Disorders   38   2020.2

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.msard.2019.101872

  • Spinal cord involvement by atrophy and associations with disability are different between multiple sclerosis and neuromyelitis optica spectrum disorder Reviewed

    Y. Nakamura, Z. Liu, S. Fukumoto, K. Shinoda, A. Sakoda, T. Matsushita, S. Hayashida, N. Isobe, M. Watanabe, A. Hiwatashi, R. Yamasaki, J. i. Kira

    European Journal of Neurology   27 ( 1 )   92 - 99   2020.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1111/ene.14038

  • Oligodendroglial connexin 47 regulates neuroinflammation upon autoimmune demyelination in a novel mouse model of multiple sclerosis Reviewed

    Yinan Zhao, Ryo Yamasaki, Hiroo Yamaguchi, Satoshi Nagata, Hayato Une, Yiwen Cui, Katsuhisa Masaki, Yuko Nakamuta, Kyoko Iinuma, Mitsuru Watanabe, Takuya Matsushita, Noriko Isobe, Jun Ichi Kira

    Proceedings of the National Academy of Sciences of the United States of America   117 ( 4 )   2160 - 2169   2020.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1073/pnas.1901294117

  • Intractable axonal neuropathy with multifocal peripheral nerve swelling in neuromyelitis optica spectrum disorders A case report Reviewed

    Yuri Mizuno, Koji Shinoda, Mitsuru Watanabe, Hidenori Ogata, Noriko Isobe, Takuya Matsushita, Ryo Yamasaki, Kimihiro Tanaka, Haruki Koike, Masahisa Katsuno, Jun ichi Kira

    Multiple Sclerosis and Related Disorders   35   16 - 18   2019.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.msard.2019.06.033

  • Long-term use of interferon-β in multiple sclerosis increases Vδ1-Vδ2-Vγ9- γδ T cells that are associated with a better outcome Reviewed

    16 ( 1 )   2019.9

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    Language：English   Publishing type：Research paper (scientific journal)  

    BACKGROUND: We previously reported that Vδ2+Vγ9+ γδ T cells were significantly decreased in multiple sclerosis (MS) patients without disease-modifying therapies (untreated MS) and were negatively correlated with Expanded Disability Status Scale (EDSS) scores, suggesting protective roles of Vδ2+Vγ9+ γδ T cells. Interferon-β (IFN-β) is one of the first-line disease-modifying drugs for MS. However, no previous studies have reported changes in γδ T cell subsets under IFN-β treatment. Therefore, we aimed to clarify the effects of the long-term usage of IFN-β on γδ T cell subsets in MS patients. METHODS: Comprehensive flow cytometric immunophenotyping was performed in 35 untreated MS and 21 MS patients on IFN-β for more than 2 years (IFN-β-treated MS) including eight super-responders fulfilling no evidence of disease activity criteria, and 44 healthy controls (HCs). RESULTS: The percentages of Vδ2+Vγ9+ cells in γδ T cells were significantly lower in untreated and IFN-β-treated MS patients than in HCs. By contrast, the percentages of Vδ1-Vδ2-Vγ9- cells in γδ T cells were markedly higher in IFN-β-treated MS patients than in HCs and untreated MS patients (both p < 0.001). A significant negative correlation between the percentages of Vδ2+Vγ9+ cells in γδ T cells and EDSS scores was confirmed in untreated MS but not evident in IFN-β-treated MS. Moreover, class-switched memory B cells were decreased in IFN-β-treated MS compared with HCs (p < 0.001) and untreated MS patients (p = 0.006). Interestingly, the percentages of Vδ1-Vδ2-Vγ9- cells in γδ T cells were negatively correlated with class-switched memory B cell percentages in all MS patients (r = - 0.369, p = 0.005), and the percentages of Vδ1-Vδ2-Vγ9- cells in Vδ1-Vδ2- γδ T cells were negatively correlated with EDSS scores only in IFN-β super-responders (r = - 0.976, p < 0.001). CONCLUSIONS: The present study suggests that long-term usage of IFN-β increases Vδ1-Vδ2-Vγ9- γδ T cells, which are associated with a better outcome, especially in IFN-β super-responders. Thus, increased Vδ1-Vδ2-Vγ9- cells together with decreased class-switched memory B cells may contribute to the suppression of disease activity in MS patients under IFN-β treatment.

    DOI： 10.1186/s12974-019-1574-5

  • MOG antibody disease manifesting as progressive cognitive deterioration and behavioral changes with primary central nervous system vasculitis Reviewed

    Toshikazu Baba, Koji Shinoda, mitsuru watanabe, Shoko Sadashima, Dai Matsuse, Noriko Isobe, Ryo Yamasaki, Kimihiko Kaneko, Toshiyuki Takahashi, Toru Iwaki, Jun-Ichi Kira

    Multiple Sclerosis and Related Disorders   30   48 - 50   2019.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.msard.2019.01.053

  • Case of central nervous system inflammatory disease in late pregnancy Reviewed

    Noriko Isobe, Toshikazu Baba, Yuri Nakamura, Koji Shinoda, Mitsuru Watanabe, Takuya Matsushita, Jun-ichi Kira

    Clinical and Experimental Neuroimmunology   10 ( S1 )   54 - 58   2019.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1111/cen3.12503

  • Short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms in NMOSD. Reviewed International journal

    Mizuno Y, Shinoda K, Watanabe M, Matsushita T, Yamasaki R, Kira J.

    Neurol Neuroimmunol Neuroinflamm   2018.3

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    Language：English   Publishing type：Research paper (scientific journal)  

  • Early and extensive spinal white matter involvement in neuromyelitis optica Reviewed International journal

    Shotaro Hayashida, Katsuhisa Masaki, Tomomi Yonekawa, Satoshi Suzuki, Hiwatashi Akio, Takuya Matsushita, Mitsuru Watanabe, Ryo Yamasaki, Toshihiko Suenaga, Toru Iwaki, Hiroyuki Murai, Jun-ichi Kira

    Brain Pathology   27 ( 3 )   249 - 265   2017.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1111/bpa.12386

  • Latitude and HLA-DRB1*04:05 independently influence disease severity in Japanese multiple sclerosis A cross-sectional study Reviewed International journal

    Yuri Nakamura, Takuya Matsushita, Shinya Sato, Masaaki Niino, Toshiyuki Fukazawa, Satoshi Yoshimura, Shin Hisahara, Noriko Isobe, Shun Shimohama, Mitsuru Watanabe, Kazuto Yoshida, Hideki Houzen, Yusei Miyazaki, Ryo Yamasaki, Seiji Kikuchi, Jun-ichi Kira

    Journal of Neuroinflammation   13 ( 1 )   2016.9

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1186/s12974-016-0695-3

  • Holocord involvement with sparing of the peripheral white matter rim in longitudinally extensive spinal cord lesions of neuromyelitis optica Reviewed International journal

    Shotaro Hayashida, Katsuhisa Masaki, Takuya Matsushita, Mitsuru Watanabe, Ryo Yamasaki, Hiroyuki Murai, Jun-Ichi Kira

    Clinical and Experimental Neuroimmunology   6   78 - 79   2015.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1111/cen3.12274

  • Copy number variations in multiple sclerosis and neuromyelitis optica Reviewed International journal

    Shinya Sato, Ken Yamamoto, Takuya Matsushita, Noriko Isobe, Yuji Kawano, Kyoko Iinuma, Masaaki Niino, Toshiyuki Fukazawa, Yuri Nakamura, Mitsuru Watanabe, Tomomi Yonekawa, Katsuhisa Masaki, Satoshi Yoshimura, Hiroyuki Murai, Ryo Yamasaki, Jun-ichi Kira

    Annals of Neurology   78 ( 5 )   762 - 774   2015.11

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1002/ana.24511

  • Anti-KIR4.1 antibodies in Japanese patients with idiopathic central nervous system demyelinating diseases Reviewed International journal

    Mitsuru Watanabe, Ryo Yamasaki, Yuji Kawano, Shihoko Imamura, Jun-ichi Kira

    Clinical and Experimental Neuroimmunology   4 ( 2 )   241 - 242   2013.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1111/cen3.12029

  • Remission of lymphomatosis cerebri induced by corticosteroid and high-doses intravenous methotrexate Reviewed

    Mitsuru Watanabe, Hitoshi Satoi, Yuki Takahashi, Namiko Nishida, Hiroki Toda, Sadayuki Matsumoto

    Clinical Neurology   52 ( 7 )   486 - 490   2012.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.5692/clinicalneurol.52.486

  • Myopathy in autoimmune polyendocrinopathy- candidiasis-ectodermal dystrophy Reviewed International journal

    Mitsuru Watanabe, Hirofumi Ochi, Hajime Arahata, Tomohito Matsuo, Seiho Nagafuchi, Yasumasa Ohyagi, Jun-ichi Kira

    Muscle and Nerve   45 ( 6 )   904 - 908   2012.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1002/mus.23321

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Presentations

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MISC

  • 二次性進行型多発性硬化症の治療とモニター

    福元尚子、渡邉充

    日本臨牀   2022.5

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • 知っておきたい免疫性神経疾患の疫学・環境要因

    渡邉充

    日本臨牀   2022.5

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • 【免疫性神経疾患(第2版)-基礎・臨床の最新知見-】中枢神経脱髄疾患　二次性進行型多発性硬化症の治療とモニター

    福元 尚子, 中村 優理, 渡邉 充

    日本臨床   80 ( 増刊5 免疫性神経疾患 )   168 - 171   2022.5   （ ISSN:0047-1852 ）

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    Language：Japanese   Publisher：(株)日本臨床社  

  • 【免疫性神経疾患(第2版)-基礎・臨床の最新知見-】知っておきたい免疫性神経疾患の疫学・環境要因

    渡邉 充

    日本臨床   80 ( 増刊5 免疫性神経疾患 )   24 - 28   2022.5   （ ISSN:0047-1852 ）

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    Language：Japanese   Publisher：(株)日本臨床社  

  • 脱髄性疾患の疾患活動性と治療反応性のモニタリング

    渡邉充

    日本臨牀   2021.10

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • 神経免疫療法（標準的医療説明） Reviewed

    渡邉充

    一般社団法人内科系学会社会保険連合，医学書院   2021.8

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • 多発性硬化症（お医者さんオンライン） Reviewed

    渡邉充、吉良潤一

    プレシジョン   2020.11

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • ライム病（スピロヘータ）

    福元尚子, 渡邉充, 吉良潤一

    2020.10

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • ミエリンベーシック蛋白（MBP）

    渡邉充, 吉良潤一

    内科   2020.4

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • 多発性硬化症と類縁疾患 Reviewed

    渡邉充

    ディサースリア臨床研究   2019.12

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • 神経免疫療法（標準的医療説明の手順書 2019年版） Reviewed

    渡邉充，吉良潤一

    （株）杏林舎   2019.8

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • 神経免疫療法 Reviewed

    渡邉充, 吉良潤一

    標準的医療説明の手順書 2019年版．一般社団法人内科系学会社会保険連合   2019.8

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • 診断基準（McDonald 2017）．

    渡邉充，吉良潤一．

    2018.11

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • Relationship between Th1 cells and astrocytic connexin 43 gap junctions in multiple sclerosis

    Mitsuru Watanabe, Ryo Yamasaki, Jun-ichi Kira

    Clinical and Experimental Neuroimmunology   2017.5

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    Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    DOI： 10.1111/cen3.12384

  • 中枢神経の自己免疫性血管炎．

    渡邉充，吉良潤一．

    神経治療   2017.5

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • 多発性硬化症の診断と治療の進歩．

    渡邉充，吉良潤一．

    日本医師会雑誌   2017.4

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • Autoantibodies to neural antigens in CNS demyelinating disorders

    Mitsuru Watanabe, Takayuki Kondo

    Current Neurobiology   2016.1

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    Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    DOI： 10.4172/0975-9042.000108

  • フィンゴリモド（多発性硬化症治療薬）．

    渡邉充，吉良潤一．

    医学のあゆみ   2014.5

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • MSとNMOの治療の将来展望．

    渡邉充，吉良潤一．

    2013.6

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • 多発性硬化症

    渡邉充，吉良潤一．

    2013.3

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

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Professional Memberships

  • Japanese Society for Neuroinfectious Diseases

  • Japanese Society of Neurological Therapeutics

  • The Japanese Society for Neuroimmunology

  • Japanese Society of Neurology

  • The Japanese Society of Internal Medicine

  • Japanese Peripheral Nerve Society

  • The Japanese Society of Clinical Immunology

  • Japan Society for Dementia Research

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Committee Memberships

  • Councilor   Domestic

    2022.10 - Present   

  • Councilor   Domestic

    2020.4 - Present   

  • 日本神経感染症学会   評議員   Domestic

    2020.4 - Present   

Academic Activities

  • Plenary session演者 International contribution

    2023.11

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    Type：Competition, symposium, etc. 

  • シンポジウム演者

    第35回日本神経免疫学会学術集会  （ 東京 ） 2023.9

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    Type：Competition, symposium, etc. 

  • Screening of academic papers

    Role(s)： Peer review

    2022

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    Type：Peer review 

    Number of peer-reviewed articles in foreign language journals：2

    Number of peer-reviewed articles in Japanese journals：0

    Proceedings of International Conference Number of peer-reviewed papers：0

    Proceedings of domestic conference Number of peer-reviewed papers：0

  • Screening of academic papers

    Role(s)： Peer review

    2021

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    Type：Peer review 

    Number of peer-reviewed articles in foreign language journals：3

    Number of peer-reviewed articles in Japanese journals：1

  • 教育コース演者

    第61回日本神経学会学術大会  （ 岡山 ） 2020.8 - 2020.9

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    Type：Competition, symposium, etc. 

  • Screening of academic papers

    Role(s)： Peer review

    2020

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    Type：Peer review 

    Number of peer-reviewed articles in foreign language journals：5

    Number of peer-reviewed articles in Japanese journals：1

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Research Projects

  • Elucidation of inflammation regulatory mechanisms in central nervous system autoimmune diseases

    Grant number：24K02371  2024.4 - 2028.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Grant type：Scientific research funding

    CiNii Research

  • Single-cell analysis of autoantigen-specific B cells in autoimmune nodopathy

    Grant number：24K10644  2024.4 - 2027.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant type：Scientific research funding

    CiNii Research

  • コネキシン43結合性マイクロRNAを介する多発性硬化症重症化機構の解明と治療開発

    Grant number：24K10666  2024.4 - 2027.3

    科学研究費助成事業  基盤研究(C)

    中村 優理, 山崎 亮, 今村 友裕, 渡邉 充, 吉良 潤一, Maimaitijiang Guzailiayi, 迫田 礼子, 真崎 勝久

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    Grant type：Scientific research funding

    エクソソームは血液脳関門を通過することから、私たちは多発性硬化症(MS)では、GJA1-29k+exosomeは、アストログリア由来で炎症性miR等を伝搬することで増悪させるとの新仮説を立てた。本研究では、(1)エクソソームに含有されるCx43-binding miRをMSの各病期で血清と髄液で解析しMSの障害度パラメーターとの関連を明らかにする。(2) MSで増加しているCx43-binding miRの培養免疫細胞やミクログリアへの作用を明らかにする。(3) 実験的自己免疫性脳脊髄炎でCx43-binding miRの病態との関連を明らかにしantagomiRによる治療を開発する。

    CiNii Research

  • CD20陽性T細胞とB細胞に注目した多発性硬化症病態の解明

    Grant number：23K06964  2023.4 - 2026.3

    科学研究費助成事業  基盤研究(C)

    篠田 紘司, 松下 拓也, 渡邉 充, 磯部 紀子, 真崎 勝久

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    Grant type：Scientific research funding

    多発性硬化症病態における主役はT細胞だと長年考えられてきたが、近年は抗CD20抗体の成功からB細胞の役割が注目されている。申請者は、抗CD20抗体治療がB細胞とT細胞両方を抗炎症性に機能変化させること、CD20陽性CD8+ T細胞が疾患活動性の予測因子となることを国際共同研究にて報告した。今後の課題は、CD20陽性T細胞の起源・体内動態・バイオマーカーとしての可能性、CD20陽性T細胞除去だけでは説明できない抗CD20抗体治療のT細胞活性抑制機構であり、本研究は、CD20陽性T細胞やB細胞を中心とした病態をより詳細に検討し、治療効果に直結する指標や新規治療標的の発見を目指すものである。

    CiNii Research

  • 免疫学的視点からみた中枢性神経障害性疼痛の病態解明ならびに新規治療法開発

    Grant number：23K06945  2023.4 - 2026.3

    科学研究費助成事業  基盤研究(C)

    藤井 敬之, 松本 省二, 山崎 亮, 渡邉 充, 磯部 紀子

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    Grant type：Scientific research funding

    末梢神経障害による末梢性神経障害性疼痛（peripheral NP: PNP）では、近年、原因の一つとして痛覚伝導路に直接作用する自己抗体の関与が明らかとなり、免疫治療による疼痛の改善が報告されている。一方、脳卒中や多発性硬化症でみられる中枢性神経障害性疼痛（central NP: CNP）では、疼痛関連自己抗体の関与は検証されていない。本研究では、CNP患者を対象とし、既知の疼痛関連自己抗体の測定に加え、未知の自己抗体の探索を行い、自己抗体介在性CNPの存在を明らかにする。そして、受動免疫モデル動物の作成を通して、その病態機序を解明する。これにより、CNPにおける新規疼痛コントロール療法の開発につなげる。

    CiNii Research

  • ヘミチャネル阻害薬を用いたαシヌクレイン伝播阻止による多系統萎縮症の治療法開発

    Grant number：23K06965  2023.4 - 2026.3

    科学研究費助成事業  基盤研究(C)

    真崎 勝久, 山口 浩雄, 山崎 亮, 渡邉 充, 吉良 潤一, 松瀬 大

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    Grant type：Scientific research funding

    私たちはオリゴデンドロサイトにおいてヒト変異αシヌクレインを髄鞘形成後に発現させることで急速に神経症状が進行する多系統萎縮症の新たなモデルマウスの開発に成功した。本モデルは小脳性運動失調や運動麻痺が明らかで発病時期や進行も速く、ヒト病態をより鋭敏に反映し、治療法開発に有用である。脱髄やオリゴデンドロサイト細胞死に先行してグリア細胞間情報伝達を担うコネキシン群が広汎に脱落することを発見し、αSyn蓄積と脳内恒常性グリアネットワーク破綻という全く新しい視点から病態解明と新規治療法開発を推進する。国内の大学および製薬企業との連携により中枢神経への移行性の高い薬剤を用い臨床応用の実現化を目指す。

    CiNii Research

  • グリアコネキシン低分子量イソフォーム発現エキソソームによる脱髄炎の悪化と治療開発

    Grant number：21K07467  2021.4 - 2024.3

    科学研究費助成事業  基盤研究(C)

    中村 優理, 山崎 亮, 今村 友裕, 渡邉 充, 吉良 潤一, Maimaitijiang Guzailiayi, 真崎 勝久

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    Grant type：Scientific research funding

    多発性硬化症(MS)は最も多い脱髄疾患で根治療法はない。私たちは剖検例でグリアコネキ シン(Cx)の脱髄巣での発現異常が重症度と相関し、MSモデルの実験的自己免疫性脳脊髄炎(EAE)で発症時に末梢血でGap junction(GJ)A1-26kD isoformを発現するエキソソームが著増することを見出した。GJA1-26kD isoform発現エキソソームが、脳皮質アストログリア由来でEAEを増悪させると考えた。本研究でアストログリア由来GJA1-26kD isoform発現エキソームが脱髄炎を遠隔性に制御している機序について明らかにする。

    CiNii Research

  • Novel therapy for spinal cord damage of neuromyelitis optica via regulation of BK channel

    Grant number：20K07869  2020.4 - 2023.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Matsushita Takuya

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    Grant type：Scientific research funding

    We investigated associations between KCNMA1, a component of BK channel, and spinal cord damage in patients with neuromyelitis optic spectrum disorders (NMOSD). Immunoreactivity in the perivascular area of the central gray matter, where aquaporin-4 (AQP4), an antigen targeted by specific autoantibodies in NMOSD, is observed. Primary astrocyte cultures exhibited KCNMA1 expression in the membrane similar to AQP4, as well as in the perikaryon. These astrocytes were damaged to death by addition of IgG purified from serum of a NMOSD patient with anti-AQP4 antibody and complements. Addition of modulator of KCNMA1, ISO or PAX , did not elicit any effects on IgG-complement-mediated damage .However, NMO-IgG addition to the cells induced translocation of NFκB into the nucleus and the translocation was inhibited by ISO and accelerated by PAX addition. These findings suggest that KCNMA1 influences CNS inflammation by promoting astrocytes to adopt a pro-inflammatory phenotype.

    CiNii Research

  • Novel therapy for progressive multiple sclerosis and multiple system atrophy by glial regulation

    Grant number：20K07889  2020.4 - 2023.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Katsuhisa Masaki

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    Grant type：Scientific research funding

    The pathological hallmark of multiple system atrophy (MSA) is aberrant accumulation of phosphorylated α-synuclein in oligodendrocytes, forming glial cytoplasmic inclusions (GCIs). Extensive demyelination occurs in the olivopontocerebellar and striatonigral pathways. Glial connexins (Cxs) play critical roles in myelin maintenance, and have not been studied in MSA. We investigated glial Cx changes in 15 autopsied patients with MSA. We classified lesions into three stages: early (Stage I), intermediate (Stage II), and late (Stage III) stages. Accumulation of phosphorylated α-synuclein in oligodendrocytes was frequently seen in Stage I but less frequently observed in Stages II and III. Even at Stage I, Cx32 was nearly absent from myelin. Cx32 was re-distributed in the oligodendrocyte cytoplasm and co-localized with GCIs. Astrocytic Cx43 was down-regulated in Stage I.Early and extensive alterations of glial Cxs occur in MSA and may accelerate demyelination.

    CiNii Research

  • A novel model of multiple sclerosis and multiple system atrophy that are differentially manifested by the time of abnormal protein expression

    Grant number：20K20470  2019.6 - 2023.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Pioneering)

    Kira Jun-ichi

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    Grant type：Scientific research funding

    We developed a novel multiple system atrophy (MSA) model by oligodendrocyte-specific over-expression of human A53T mutant α-synuclein in adult mice using Tet-Off regulation. Transgenic mice presented rapidly progressive ataxia and prominent demyelination in the brainstem/cerebellum with phosphorylated α-synuclein accumulation and substantial glial activation. With late re-inhibition of α-synuclein production, clinicopathological deterioration persisted despite the resolution of aggregated α-synuclein. Single-cell RNA sequencing of brain CD11b+ cells revealed a unique microglia cluster highly expressing Tlr2, Tgm2, Arg1, Msr1, and inflammatory cytokine genes that surrounded phosphorylated α-synuclein aggregates. Prophylactic administration of a colony-stimulating factor 1 receptor inhibitor increased these α-synuclein-associated microglia and worsened demyelination. Thus, a unique α-synuclein-associated microglia subset engages in progressive demyelination and neurodegeneration.

    CiNii Research

  • 多発性硬化症患者のフローサイトメトリー

    2018.4

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    Authorship：Principal investigator 

    多発性硬化症患者の末梢血免疫細胞の解析を通じて病態解明につなげる

  • 多発性硬化症患者および視神経脊髄炎スペクトラム障害の血中・髄液中バイオマーカー探索 International coauthorship

    2018.1

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    Authorship：Principal investigator 

    多発性硬化症患者および視神経脊髄炎関連疾患患者の髄液中・血中のGFAPおよびニューロフィラメント軽鎖に加え、好中球関連マーカーの濃度を測定し、臨床データとの相関を評価し、バイオマーカーとしての有用性を評価する。

  • T細胞によるグリアコネキシン喪失機構の解明とそれに基づく脱髄疾患の新規治療法開発

    Grant number：15K19489  2015 - 2016

    科学研究費助成事業  若手研究(B)

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    Authorship：Principal investigator  Grant type：Scientific research funding

  • 遺伝環境リスクと病態特異的抗神経分子抗体に基づく脱髄疾患の自己免疫機構解明と治療

    Grant number：19H01045 

    吉良 潤一, 松下 拓也, 山崎 亮, 藤井 敬之, 緒方 英紀, 磯部 紀子, 萬谷 博, 海田 賢一, 渡邉 充, 中村 優理

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    Grant type：Scientific research funding

    慢性脱髄疾患として中枢神経を侵す多発性硬化症(MS)と末梢神経を侵す慢性炎症性脱髄性多発神経炎(CIDP)が代表的である。私達は神経根肥厚を呈するCIDPで、IgG4抗NF155抗体が陽性で、全例がMSのリスク遺伝子と同じHLA-DRB1*15を保有することを発見した。また、MS類縁疾患のアトピー性脊髄炎で抗Plexin D1抗体が陽性であることを見出した。MSの環境リスクとしてピロリ菌感染や米食の減少を同定した。本研究では慢性脱髄疾患を対象とし遺伝環境リスクを背景に病態特異的自己抗体の産生を伴う自己免疫が成立する過程を解明し、病態バイオマーカーの確立とモデル動物作成による新規治療開発を行う。

    CiNii Research

  • 日本人多発性硬化症での疾患修飾薬による進行性多巣性白質脳症多発機序の解明と防止

    Grant number：19K07997 

    河野 祐治, 松下 拓也, 渡邉 充, 中村 優理, 磯部 紀子

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    Grant type：Scientific research funding

    多発性硬化症(MS)は、疾患修飾薬により再発を減らすことが可能になったが、重大な副作用として長期使用に伴い潜伏感染しているJC virus (JCV)が起こす進行性多巣性白質脳症(PML)がある。特に日本人では欧米人の約10倍のPML発症がみられ、大きな問題になっている。本研究ではPML発症が多い理由の解明、PML発症リスク因子の同定と発症予測バイオマーカーの確立を目的とする。そのため、全ゲノム関連解析によるJCV感染の感受性遺伝子の同定、HLA多型とJCV特異的T細胞(CD8/CD4)の頻度及びT細胞の認識するJCV抗原エピトープの同定、疾患修飾薬によるこれらの変化等を解析する。

    CiNii Research

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Outline of Social Contribution and International Cooperation activities

  • 大学病院の外来診療や治験協力を通して社会貢献を行っている。
    また多発性硬化症や視神経脊髄炎スペクトラム障害、重症筋無力症などの臨床・研究を通じて、患者の症状・予後の改善を目指している。
    さらに他施設の医師や製薬企業などとともに該当疾患に関連する講演会やディスカッションを積極的に行い、疾患や治療の普及・患者ごとの治療の適正化に貢献している。

Social Activities

  • 「多発性硬化症の診断と治療のトレンド」という題目で某大学の医師向けに講演を行うとともに、多発性硬化症診療について議論を行った。

    ノバルティスファーマ  大阪・枚方  2024.3

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「Efgartigimodの使用経験と期待～EFT/FTとしての有用性～」という題目で講演をするとともに、参加者らとディスカッションを行った

    アルジェニクスジャパン  福岡  2024.3

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「新ガイドラインから考える最適なMS治療戦略～日本人MSの特徴と活動性の評価～」という演題で講演を行うとともに、ほかの専門医の先生方と日本人における多発性硬化症診療についてのディスカッションを行った。

    バイオジェン・ジャパン  東京  2024.2

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「重症筋無力症の病態・疫学・診断・治療」という題目で当該企業の社員向けの講義を行った

    某製薬会社  福岡  2024.2

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Seminar, workshop

  • 「新ガイドラインを踏まえた日本人におけるMS治療戦略」という題目で某大学およびその関連病院の脳神経内科医向けに講演を行った。

    バイオジェン・ジャパン  熊本  2024.2

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「新ガイドラインを考慮したこれからのMS治療戦略（初期治療としてのケシンプタの可能性）」という題目で多発性硬化症診療に携わる医師向けに講演を行った

    ノバルティスファーマ  2024.1

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「多発性硬化症の治療戦略とバイオマーカーへの期待」という題目で某大学の医師向けに講演を行うとともに、多発性硬化症や視神経脊髄炎診療について議論を行った。

    第一三共株式会社  横浜  2024.1

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「日本人におけるMS治療戦略update」という演題で九州の脳神経内科医向けに講演を行った。

    バイオジェン・ジャパン  福岡  2023.12

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「多発性硬化症の診断と新たな治療戦略」という題目で福岡の脳神経内科医向けに講演を行うとともに、多発性硬化症やパーキンソン病と消化器症状について議論を行った。

    ヴィアトリス製薬株式会社  福岡  2023.12

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「オファツムマブを用いた長期予後を考慮したMS治療戦略」という題目で全国の多発性硬化症診療に携わる医師向けに講演を行った

    ノバルティスファーマ  2023.12

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「全身型重症筋無力症の治療戦略と抗補体製剤の使い方」という演題で九州の脳神経内科医向けに講演を行った。

    日本神経学会九州地方会・アレクシオンファーマ  宮崎  2023.12

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「NMOSDの治療方針～新ガイドラインを中心に～」という題目で当該企業の社員向けの講義を行った

    某製薬会社  福岡  2023.11

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Seminar, workshop

  • 「日本人における多発性硬化症の治療戦略とフマル酸ジメチルの位置付け」という題目で全国の医師向けに講演を行った。

    バイオジェン・ジャパン  福岡  2023.9

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「多発性硬化症の診断と治療のトレンド」という題目で講演を行った

    ノバルティスファーマ  2023.9

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 多発性硬化症診療を行う若手の医師とともに症例をもとにディスカッションを行い、重要な考え方について共有をした。

    バイオジェン・ジャパン  東京  2023.6

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「日本人のMSにおけるテクフィデラの治療戦略を考える～臨床的見地から～」という題目で講演を行うとともに、ほかの専門医の先生方と多発性硬化症診療についての意見交換を行った。

    バイオジェン・ジャパン  福岡  2023.6

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「多発性硬化症におけるB細胞の関与とB細胞除去療法」という題目で講演を行った

    ノバルティスファーマ  2023.5

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「多発性硬化症の診断と治療のトレンド（B細胞除去療法の位置付けを含めて）」という題目で講演を行うとともに、多発性硬化症診療に携わる他施設の医師とディスカッションを行った

    ノバルティスファーマ  2023.5

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「gMG診療の課題（医師視点）」という題目でディスカッションを行った

    アルジェニクスジャパン  東京  2023.4

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Other

  • 「日本人の特徴をふまえたMS診療とバイオマーカーへの期待」という題目で講演を行った

    バイオジェン・ジャパン  2023.3

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「テクフィデラの至適患者像とは？～日本人MS患者の特徴を踏まえて～」という題目で講演を行った

    バイオジェン・ジャパン  東京（ハイブリッド）  2023.2

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 前年度に引き続き多発性硬化症・視神経脊髄炎診療ガイドラインの作成に、システマティックレビュー委員として参加し、2023年9月に発刊された。

    2023

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    前年度に引き続き多発性硬化症・視神経脊髄炎診療ガイドラインの作成に、システマティックレビュー委員として参加し、2023年9月に発刊された。

  • 「臨床症状のない再発、再発のない進行を理解する」という題目で講演を行った

    ノバルティスファーマ  2022.12

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「当院でのウィフガート使用経験」という題目で講演を行った

    アルジェニクスジャパン  福岡（ハイブリッド）  2022.10

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「日本人多発性硬化症の特徴」という題目で講演を行った

    ノバルティスファーマ  2022.10

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「NMOSDの治療方針～ユプリズナ使用の実際も含めて～」という題目で講演を行った

    田辺三菱製薬  福岡（ハイブリッド）  2022.9

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「MSの正しい診断～MSらしさとは～」という題目で講演を行った

    ノバルティスファーマ  2022.8

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「当院でのウィフガート使用経験」という題目で講演を行った

    アルジェニクスジャパン  福岡（ハイブリッド）  2022.8

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「二次性進行型多発性硬化症への治療戦略と当院での治療経験」という題目で講演を行った

    ノバルティスファーマ  2022.5

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「NMOSD患者のモニタリングにおける血清GFAP測定への期待と課題」という題目で当該企業の社員向けの講義を行った

    某製薬会社  2022.3

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Seminar, workshop

  • 前年度に引き続き多発性硬化症・視神経脊髄炎診療ガイドラインの作成に、システマティックレビュー委員として参加した。

    2022

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    前年度に引き続き多発性硬化症・視神経脊髄炎診療ガイドラインの作成に、システマティックレビュー委員として参加した。

  • 「多発性硬化症診療のポイントとB細胞除去療法の位置づけ」という題目で某大学向けに講演を行った

    ノバルティスファーマ  2021.12

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 「NMOSDのバイオマーカー」という題目で当該企業の社員向けの講義を行った

    某製薬会社  2021.7

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Seminar, workshop

  • 「多発性硬化症診療のコツと注意点」というタイトルで千葉県某病院向けに講演を行った

    ノバルティスファーマ  2021.6

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

  • 多発性硬化症・視神経脊髄炎診療ガイドラインの作成に、システマティックレビュー委員として参加している。

    2021

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    多発性硬化症・視神経脊髄炎診療ガイドラインの作成に、システマティックレビュー委員として参加している。

  • 「多発性硬化症における免疫とバイオマーカー研究～治療の最適化を目指して～」というタイトルで某大学向けに講演を行った

    ノバルティスファーマ  2020.11

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    Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Lecture

▼display all

Specialized clinical area

  • Biology / Medicine, Dentistry and Pharmacy / Internal Medicine / Neurology

    神経免疫疾患

Clinician qualification

  • Specialist

    Japanese Society of Neurology

  • Specialist

    The Japanese Society of Internal Medicine（JSIM）

  • Preceptor

    Japanese Society of Neurology

Year of medical license acquisition

  • 2006

Notable Clinical Activities

  • 多発性硬化症や視神経脊髄炎スペクトラム障害、重症筋無力症などの神経免疫疾患の専門外来を行っている。