Clinical and histological features of inflammatory myopathies mediated by autoantibodies

• Project/Area Number: 26461298
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Keio University
• Principal Investigator: Suzuki Shigeaki 慶應義塾大学, 医学部(信濃町), 講師 (50276242)
• Research Collaborator: NISHINO Ichizo ; OHNUKI Yuko ; WATANABE Yurika
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 自己抗体 / 炎症性筋疾患 / 免疫介在性壊死性ミオパチー / SRP / HMGCR / 壊死性ミオパチー / 壊死性筋症 / スタチン / 筋病理 / 免疫沈降法

Outline of Final Research Achievements

Immune-mediated necrotizing myopathy (IMNM) is a pathological entity characterized by necrosis in the absence of prominent endomysial lymphocytic infiltration. Autoantibodies against signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are associated with IMNM. The frequencies of anti-SRP and anti-HMGCR antibodies in patients with IMNM were 39% and 25%, respectively. Severe limb muscle weakness, neck weakness, dysphagia, respiratory insufficiency, and muscle atrophy were more frequently observed in patients with anti-SRP antibodies than with anti-HMGCR antibodies. HLA-DRB1 genotyping revealed the association of anti-SRP antibodies with DRB1*08:03 and that of anti-HMGCR antibodies with DRB1*11:01.

Research Products

• [Journal Article] Pediatric necrotizing myopathy associated with anti-3-hydroxy-3-methylglutary coenzyme A reductase antibodies (2017)
  • Author(s): Liang WC, Uruha A, Suzuki S, Murakami N, Takeshita E, Chen WZ, Jong WJ, Endo Y, Komaki H, Fujii T, Sekine H, Suzuki Y, Kawano Y, Mori-Yoshimura M, Oya Y, Xi J, Zhu W, Zhao C, Watanabe Y, Ikemoto K, Nishikawa A, Hamanaka K, Mitsuhashi S, Suzuki N, Nishino I.
  • Journal Title: Rheumatology Volume: 56 Issue: 2 Pages: 287-293
  • DOI: 10.1093/rheumatology/kew386
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical features and prognosis in anti-SRP and anti-HMGCR necrotizing myopathy. (2016)
  • Author(s): Watanabe Y, Uruha A, Suzuki S, Nakahara J, Hamanaka K, Takayama K, Suzuki N, Nishino I．
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 87 Issue: 10 Pages: 1038-1044
  • DOI: 10.1136/jnnp-2016-313166
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] HLA-DRB1 alleles in immune-mediated necrotizing myopathy. (2016)
  • Author(s): Ohnuki Y, Suzuki S, Shiina T, Uruha A, Watanabe Y, Suzuki S, Izumi S, Nakahara J, Hamanaka K, Takayama K, Suzuki N, Nishino I.
  • Journal Title: Neruology Volume: 87 Issue: 18 Pages: 1954-1955
  • DOI: 10.1212/wnl.0000000000003160
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association between glucocorticoid-induced osteoporosis and myasthenia gravis: a cross-sectional study. (2015)
  • Author(s): Konno S, Suzuki S, Masuda M, et al.
  • Journal Title: PLoS One Volume: 10 Issue: 5 Pages: e0126579-e0126579
  • DOI: 10.1371/journal.pone.0126579
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inflammatory myopathy with anti-signal recognition particle antibodies: case series of 100 patients. (2015)
  • Author(s): Suzuki S, Nishikawa A, Kuwana M, et al.
  • Journal Title: Orphanet J Rare Dis Volume: 10 Issue: 1 Pages: 61-61
  • DOI: 10.1186/s13023-015-0277-y
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Anti-signal recognition particle antibody in patients without inflammatory myopathy: a survey of 6180 patients with connective tissue diseases. (2015)
  • Author(s): Hanaoka H, Kaneko Y, Suzuki S, et al.
  • Journal Title: Scand J Rheumatol Volume: 45 Pages: 36-40
  • Peer Reviewed
• [Journal Article] Statins and myotoxic effects associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autiantibodies: an observational study in Japan (2015)
  • Author(s): Watanabe Y, Suzuki S, Nishimura H, Murata K, Kurashige T, Ikawa M, Asahi M, Konishi H, Mitsuma S, Kawabata S, Suzuki N, Nishino I
  • Journal Title: Medicine Volume: 94 Issue: 4 Pages: e416-e416
  • DOI: 10.1097/md.0000000000000416
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clinical and histological findings associated with autoantibodies detected by RNA immunoprecipitation. (2014)
  • Author(s): Suzuki S, Yonakawa T, Kuwana M, Hayashi YK, Okazaki Y, Kawaguchi Y, Suzuki N, Nishino I
  • Journal Title: Ｊ Neuroimmunol Volume: 274 Issue: 1-2 Pages: 202-208
  • DOI: 10.1016/j.jneuroim.2014.07.006
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 壊死性ミオパチーにおける免疫治療と神経学的予後：抗SRP抗体と抗HMGCR抗体の比較． (2016)
  • Author(s): 渡邊由里香，鈴木重明，漆葉章典，濱中耕平，中原仁，高山和子，鈴木則宏，西野一三．
  • Organizer: 第34回日本神経治療学会総会
  • Place of Presentation: 米子コンベンションセンターBIGSIP（鳥取県米子市）
  • Year and Date: 2016-11-04
• [Presentation] 免疫介在性壊死性ミオパチーとHLA-DRB1遺伝子多型との関連解析． (2016)
  • Author(s): 大貫優子，鈴木重明，渡邊由里香，中原仁，鈴木進悟，鈴木則宏，椎名隆，西野一三．
  • Organizer: 第28回日本神経免疫学会学術集会
  • Place of Presentation: 長崎ブリックホール（長崎県長崎市）
  • Year and Date: 2016-09-30
• [Presentation] 壊死性ミオパチー関連自己抗体である抗SRP抗体と抗HMGCR抗体の相違点． (2016)
  • Author(s): 渡邊由里香，鈴木重明，漆葉章典，中原仁，鈴木則宏，西野一三．
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2016-05-18
• [Presentation] 炎症性筋疾患の新たな展開：anti-SRP myopathy (2014)
  • Author(s): 鈴木重明
  • Organizer: 第32回日本神経治療学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-20 – 2014-11-22
  • Invited
• [Book] Annual Review 神経 2017. 免疫性筋疾患とHLA． (2016)
  • Author(s): 鈴木重明，大貫優子，椎名隆．
  • Total Pages: 284
  • Publisher: 中外医学社
• [Remarks] 慶應義塾大学医学部神経免疫グループ
  • URL: http://www.keio-med.jp/neurology/nig/index.html
• [Remarks] 慶應義塾大学神経免疫グループホームページ
  • URL: http://www.keio-med.jp/neurology/nig/index.html
• [Funded Workshop] The 13th International Workshop on Autoantibodies and autoimmunity (2016)
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2016-10-11