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• Longitudinal MuSK antibody levels may correlate with disease severity in MuSK myasthenia gravis

  Yasuda, M; Uzawa, A; Ogaya, E; Handa, H; Kurumada, K; Takasaka, K; Akamine, H; Ozawa, Y; Kuwabara, S

  JOURNAL OF NEUROIMMUNOLOGY ( Journal of Neuroimmunology )  414   578876 - 578876   2026年05月 [ 査読有り ]

  掲載種別: 研究論文（学術雑誌）

  　概要を見る

  BACKGROUND: In muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG), the clinical utility of MuSK antibody levels as a biomarker for disease severity is debated, with conflicting reports on its correlation with clinical status. This study aimed to clarify this association by applying a rigorous statistical model to a longitudinal dataset followed from an immunotherapy-naïve state. METHODS: We conducted a retrospective longitudinal study on 6 patients with MuSK-MG tracked from their treatment-naïve baseline. The primary analysis used 103 data points where MuSK antibody levels and MG activities of daily living (MG-ADL) scores were available. A secondary analysis used the subset of 81 data points where total immunoglobulin G (IgG) levels were also concurrently measured. Generalized linear mixed-effects models (GLMM) were used to assess the intrapatient correlation, adjusting for interpatient variability by including a random intercept for each subject. RESULTS: First, the GLMM analysis of 103 data points revealed a strong positive intrapatient correlation between MuSK antibody levels and MG-ADL scores (P < 0.001). Second, in the subset analysis (n = 81), MuSK antibody levels remained positively and specifically correlated with MG-ADL scores (P = 0.002), whereas total IgG levels showed no independent correlation (P = 0.61) when included in the same model. CONCLUSIONS: MuSK antibody level, unlike total IgG, is a specific and valuable biomarker for monitoring intrapatient disease activity and therapeutic response. These findings strongly support the utility of serial MuSK antibody monitoring within individual patients.

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• Serum from patients with acetylcholine receptor antibody-positive myasthenia gravis triggers pathogenic changes in human myotube cells.

  Keisuke Tanaka, Akiyuki Uzawa, Manato Yasuda, Yosuke Onishi, Hiroyuki Akamine, Hideo Handa, Etsuko Ogaya, Shota Miyake, Masayuki Baba, Hiroto Abe, Koki Nagaoka, Yuko Nakatake-Furuie, Kenichi Serizawa, Satoshi Kuwabara

  Journal of neuroimmunology   413   578871 - 578871   2026年04月 [ 査読有り ]

  掲載種別: 研究論文（学術雑誌）

  　概要を見る

  BACKGROUND: Some patients with myasthenia gravis (MG) are refractory to available treatments, highlighting the need to further understand the pathogenesis of the disease. This study aimed to determine whether components in the serum from patients with acetylcholine receptor (AChR) antibody-positive MG affect myotubes, to explore their possible role in disease pathogenesis beyond the inhibition of acetylcholine signal transmission. METHODS: Serum was collected from 14 patients with AChR antibody-positive MG. The differentiated human myotubes were stimulated with 10% serum from healthy controls or patients with MG. After 24 h, ribonucleic acid extraction/sequencing was performed, and differentially expressed genes (DEGs) were extracted. Pathway analysis was completed using DEGs that were downregulated by stimulation with serum from patients with MG. Expression of genes important for muscle contraction was measured and myotube diameter was determined by immunostaining. RESULTS: Approximately 1200 DEGs were extracted by comparing gene expression in cultured human myotube cells stimulated with serum from healthy controls and patients with MG. Gene ontology terms linked with muscle function were suppressed in myotube cells stimulated with patient serum. Suppression of pathways associated with muscle atrophy/weakness, decreased expression of genes associated with muscle contraction, and smaller myotube diameter were confirmed in myotube cells stimulated with serum from patients versus healthy controls. CONCLUSION: Factors other than acetylcholine signal transmission inhibition may contribute to the pathogenesis of AChR antibody-positive MG. Further research is needed to clarify the pathways involved, potentially leading to more tailored pharmacotherapies.

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• Association between Myasthenia Gravis and Smoking.

  Akamine H, Uzawa A, Kuwabara S, Suzuki S, Onishi Y, Yasuda M, Ozawa Y, Kawaguchi N, Kubota T, P Takahashi M, Suzuki Y, Watanabe G, Kimura T, Sugimoto T, Samukawa M, Minami N, Masuda M, Konno S, Nagane Y, Utsugisawa K

  Internal medicine (Tokyo, Japan) ( 一般社団法人 日本内科学会 )  64 ( 24 ) 3478 - 3485   2025年12月

  掲載種別: 研究論文（学術雑誌）

  　概要を見る

  <p><b>Objective </b>This study investigated the association between smoking and myasthenia gravis (MG), a chronic autoimmune disorder that affects neuromuscular junctions. </p><p><b>Methods </b>Data were collected from the Japan MG Registry 2021 survey conducted between April and October 2021. MG severity was assessed using the MG activities of daily living score and MG Foundation of America (MGFA) classification. The Brinkman Index, calculated as the number of cigarettes smoked per day multiplied by the number of years smoked, was used to evaluate the correlation between smoking exposure and MG severity. We also compared the smoking rates of individuals with and without MG stratified by age and sex. </p><p><b>Results </b>Of the 1,402 patients selected from the Japanese registry, higher smoking rates were observed in patients with MG than in the general population. Compared with never-smokers, women with MG who smoked were younger and had a higher prevalence of ocular symptoms. A weak correlation was observed between MGFA and Brinkman indices among men with MG who smoked. No correlation was observed between smoking status and MG severity in women who smoked. </p><p><b>Conclusion </b>This study utilized one of the largest datasets on MG and smoking; thus, it provides valuable insights into the association between smoking and MG. </p>

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• Association of baseline acetylcholine receptor antibody levels with efgartigimod treatment efficacy for patients with myasthenia gravis

  Handa, H; Uzawa, A; Yasuda, M; Akamine, H; Onishi, Y; Ogaya, E; Kurumada, K; Takasaka, K; Kuwabara, S

  JOURNAL OF THE NEUROLOGICAL SCIENCES ( Journal of the Neurological Sciences )  479   123745 - 123745   2025年12月 [ 査読有り ]

  掲載種別: 研究論文（学術雑誌）

  　概要を見る

  BACKGROUND: Efgartigimod is effective for many patients with acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (gMG). To help identify patients most likely to benefit from efgartigimod, we examined the correlation between baseline AChR antibody levels and clinical response. METHODS: This retrospective observational study included 10 AChR antibody-positive MG patients receiving efgartigimod at a single center. Clinical responses were assessed by MG Activities of Daily Living (MG-ADL) scores before treatment as well as 15 and 29 days after treatment initiation. RESULTS: Patients demonstrated clinical improvement by day 15 as indicated by improved total MG-ADL score (mean, 3.6; range, -1 to 9; p = 0.0055), and condition improved further by day 29 (mean, 5.2; range, 2-10; p = 0.0003). Serum AChR antibody levels at baseline were positively correlated with MG-ADL score improvement on day 29 (r = 0.6483, p = 0.0426). CONCLUSIONS: Generalized MG patients with high baseline AChR antibody levels may exhibit a superior response to efgartigimod.

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• Predicting achievement of clinical goals using machine learning in myasthenia gravis

  Akamine, H; Uzawa, A; Kuwabara, S; Suzuki, S; Onishi, Y; Yasuda, M; Ozawa, Y; Kawaguchi, N; Kubota, T; Takahashi, MP; Suzuki, Y; Watanabe, G; Kimura, T; Sugimoto, T; Samukawa, M; Minami, N; Masuda, M; Konno, S; Nagane, Y; Utsugisawa, K

  PLOS ONE   20 ( 8 )   2025年08月 [ 査読有り ]

  掲載種別: 研究論文（学術雑誌）

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• 日常診療の質が上がる新常識 : 疾患、治療法、薬剤など明日からの診療が変わる21項目

  神里尚美, 赤嶺博行, 林 成峰 ( 担当: 分担執筆 , 担当範囲: Parkinson病治療薬の新常識 〜L-DOPA持続経腸療法（LCIG）を中心に )

  羊土社  2020年08月 ( ページ数: 226p )

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• 50歳未満発症の成人胸腺腫非合併AChR抗体陽性重症筋無力症における発症年齢階層別特徴

  安田 真人, 鵜沢 顕之, 大西 庸介, 赤嶺 博行, 小澤 由希子, 川口 直樹, 寒川 真, 久保田 智哉, 増田 眞之, 紺野 晋吾, 南 尚哉, 杉本 太路, 鈴木 靖士, 渡辺 源也, 高橋 正紀, 鈴木 重明, 長根 百合子, 槍澤 公明, 桑原 聡

  臨床神経学  1900年01月  -  1900年01月   

• 高齢発症重症筋無力症の末梢血におけるSingle cell RNA解析

  赤嶺 博行, 鵜沢 顕之, 横山 真隆, 半田 秀雄, 鋸屋 悦子, 大西 庸介, 安田 真人, 田中 知明, 桑原 聡

  神経免疫学  1900年01月  -  1900年01月   

• 高齢発症重症筋無力症における糖代謝異常と予後との関連についての解析

  安田 真人, 鵜沢 顕之, 大西 庸介, 赤嶺 博行, 鋸屋 悦子, 半田 秀雄, 小澤 由希子, 氷室 圭一, 桑原 聡

  神経治療学  1900年01月  -  1900年01月   

• 重症筋無力症治療と成果の時代変遷　Japan MG Registry study 2021からの考察

  大西 庸介, 鵜沢 顕之, 安田 真人, 赤嶺 博行, 小澤 由希子, 川口 直樹, 久保田 智哉, 増田 眞之, 紺野 晋吾, 南 尚哉, 木村 卓, 杉本 太路, 鈴木 靖士, 渡辺 源也, 高橋 正紀, 鈴木 重明, 長根 百合子, 槍澤 公明, 桑原 聡

  臨床神経学  1900年01月  -  1900年01月   

• 重症筋無力症患者の血清における補体制御因子CD59の評価(Evaluation of the complement regulatory factor CD59 in serum of patients with myasthenia gravis)

  Ogaya Etsuko, Uzawa Akiyuki, Yasuda Manato, Ozawa Yukiko, Onishi Yosuke, Akamine Hiroyuki, Handa Hideo, Masuda Hiroki, Mori Masahiro, Kuwabara Satoshi

  臨床神経学  1900年01月  -  1900年01月   

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• ウェアラブルデバイスとAI を用いた重症筋無力症の客観的症状評価システムの開発

  ■■■

  課題番号: 00000000

  研究期間: 2026年01月  -  2027年03月 

  代表者: 赤嶺博行,鵜沢顕之,楠瀬賢也 

• 重症筋無力症におけるウェアラブルデバイスによるモニタリングシステムの開発

  ■■■

  課題番号: 00000000

  研究期間: 2025年10月  -  2026年03月 

  代表者: 赤嶺博行 

• 血管内皮細胞の心臓特異性がもたらす動脈硬化リスクの解明

  基盤研究(C)

  課題番号: 23K07571

  研究期間: 2023年04月  -  2026年03月 

  代表者: 横山 真隆, 中山 哲俊, 赤嶺 博行 

  直接経費: 3,600,000（円）  間接経費: 4,680,000（円）  金額合計: 1,080,000（円）

• シングルセルRNA解析を用いた重症筋無力症の分子病態解明

  基盤研究(C)

  課題番号: 22K07343

  研究期間: 2022年04月  -  2026年03月 

  代表者: 赤嶺 博行, 鵜沢 顕之, 横山 真隆 

  直接経費: 3,200,000（円）  間接経費: 4,160,000（円）  金額合計: 960,000（円）