Analysis for Detection of Immunogenic Site on Aquaporin-4 in Neuromyelitis Optica

• Project/Area Number: 23591232
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Chiba University
• Principal Investigator: MASAHIRO Mori 千葉大学, 医学部附属病院, 講師 (70345023)
• Co-Investigator(Kenkyū-buntansha): HIWASA Takaki 千葉大学, 医学研究院, 准教授 (30260251) ; KUNIMATSU Toshimi 名古屋女子大学, 家政学部, 教授 (70145746)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 神経免疫疾患 / 視神経脊髄炎 / 多発性硬化症 / 抗アクアポリン４抗体 / aquaporin-4 / 抗体

Research Abstract

We performed anlysis using arrays consisting synthesized 156 peptides using peptide library data from entire human aquaporin-4 (AQP4) 'isoform a' sequences on a cellulose membrane. These peptides were reacted with serum samples obtained from 22 individuals with neuromyelitis optic (NMO), and 8 disease/normal controls. As a result, we can detect the immunogenic site on AQP4 that is recognized by the anti-AQP4 antibody in NMO patients. A peptides derived from an extracellular loop A of AQP4 may be a central immunogenic site on AQP4 in NMO. We have presented these resutls in domestic and international conferences.

Research Products

• [Journal Article] Bright spotty lesions on spinal magnetic resonance imaging differentiate neuromyelitis optica from multiple sclerosis (2014)
  • Author(s): Yonezu T, Ito S, Mori M, Ogawa Y, Makino T, Uzawa A, Kuwabara S
  • Journal Title: Mult Scler Volume: 20(3) Pages: 331-7
• [Journal Article] Neuromyelitis optica : concept, immunology and treatment (2014)
  • Author(s): Uzawa A, Mori M, Kuwabara S
  • Journal Title: J Clin Neurosci Volume: 21(1) Pages: 12-21
• [Journal Article] A case of fulminant neuromyelitis optica presenting with destructive lesions in whole-brain (2014)
  • Author(s): Sugiyama A, Ito S, Hirano S, Mori M, Kuwabara S
  • Journal Title: Clin Neurol Neurosurg Volume: 116 Pages: 87-9
• [Journal Article] A case of fulminant neuromyelitis optica presenting with destructive lesions in whole-brain. (2014)
  • Author(s): Sugiyama A, Ito S, Hirano S, Mori M, Kuwabara S.
  • Journal Title: Clin Neurol Neurosurg. Volume: 116 Pages: 87-89
  • DOI: 10.1016/j.clineuro.2013.11.002
  • Peer Reviewed
• [Journal Article] Neuromyelitis optica: concept, immunology and treatment. (2014)
  • Author(s): Uzawa A, Mori M, Kuwabara S.
  • Journal Title: J Clin Neurosci. Volume: 21 Issue: 1 Pages: 12-21
  • DOI: 10.1016/j.jocn.2012.12.022
  • Peer Reviewed
• [Journal Article] "Bright spotty lesions" on spinal magnetic resonance imaging differentiate neuromyelitis optica from multiple sclerosis. (2014)
  • Author(s): Yonezu T, Ito S, Mori M, Ogawa Y, Makino T, Uzawa A, Kuwabara S.
  • Journal Title: Mult Scler. Volume: 20 Issue: 3 Pages: 331-337
  • DOI: 10.1177/1352458513495581
  • Peer Reviewed
• [Journal Article] Anti-aquaporin-4 antibody-seronegative NMO spectrum disorder with Baló's concentric lesions(Review) (2013)
  • Author(s): Masuda H, Mori M, Katayama K, Kikkawa Y, Kuwabara S
  • Journal Title: Intern Med Volume: 52(13)(Epub 2013 Jul 1) Pages: 1517-21
• [Journal Article] Cerebrospinal fluid interleukin-6 and glial fibrillary acidic protein levels are increased during initial neuromyelitis optica attacks (2013)
  • Author(s): Uzawa A, Mori M, Sawai S, Masuda S, Muto M, Uchida T, Ito S, Nomura F, Kuwabara S
  • Journal Title: Clin Chim Acta Volume: 5;421 Pages: 181-3
• [Journal Article] CSF high-mobility group box 1 is associated with intrathecal inflammation and astrocytic damage in neuromyelitis optica (2013)
  • Author(s): Uzawa A, Mori M, Masuda S, Muto M, Kuwabara S
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 84(5) Pages: 517-22
• [Journal Article] Diffuse and heterogeneous T2-hyperintense lesions in the splenium are characteristic of neuromyelitis optica (2013)
  • Author(s): Makino T, Ito S, Mori M, Yonezu T, Ogawa Y, Kuwabara S
  • Journal Title: Mult Scler Volume: 19(3) Pages: 308-15
• [Journal Article] Seasonality of multiple sclerosis and neuromyelitis optica exacerbations in Japan (2013)
  • Author(s): Muto M, Mori M, Sato Y, Uzawa A, Masuda S, Kuwabara S
  • Journal Title: Mult Scler Volume: 19(3) Pages: 378-9
• [Journal Article] Anti-aquaporin-4 antibody-seronegative NMO spectrum disorder with Baló's concentric lesions. (2013)
  • Author(s): Masuda H, Mori M, Katayama K, Kikkawa Y, Kuwabara S.
  • Journal Title: Intern Med. Volume: 52 Pages: 1517-1521
  • Peer Reviewed
• [Journal Article] Cerebrospinal fluid interleukin-6 and glial fibrillary acidic protein levels are increased during initial neuromyelitis optica attacks. (2013)
  • Author(s): Uzawa A, Mori M, Sawai S, Masuda S, Muto M, Uchida T, Ito S, Nomura F, Kuwabara S.
  • Journal Title: Clin Chim Acta. Volume: 421 Pages: 181-183
  • DOI: 10.1016/j.cca.2013.03.020
  • Peer Reviewed
• [Journal Article] CSF high-mobility group box 1 is associated with intrathecal inflammation and astrocytic damage in neuromyelitis optica. (2013)
  • Author(s): Uzawa A, Mori M, Masuda S, Muto M, Kuwabara S.
  • Journal Title: J Neurol Neurosurg Psychiatry. Volume: 84 Issue: 5 Pages: 517-522
  • DOI: 10.1136/jnnp-2012-304039
  • Peer Reviewed
• [Journal Article] Diffuse and heterogeneous T2-hyperintense lesions in the splenium are characteristic of neuromyelitis optica. (2013)
  • Author(s): Makino T, Ito S, Mori M, Yonezu T, Ogawa Y, Kuwabara S.
  • Journal Title: Mult Scler. Volume: 19 Issue: 3 Pages: 308-315
  • DOI: 10.1177/1352458512454772
  • Peer Reviewed
• [Journal Article] Seasonality of multiple sclerosis and neuromyelitis optica exacerbations in Japan. (2013)
  • Author(s): Muto M, Mori M, Sato Y, Uzawa A, Masuda S, Kuwabara S.
  • Journal Title: Mult Scler. Volume: 19 Issue: 3 Pages: 378-379
  • DOI: 10.1177/1352458512452332
  • Peer Reviewed
• [Journal Article] When is neuromyelitis optica diagnosed after disease onset? (2012)
  • Author(s): Uzawa A, Mori M, Muto M, Masuda S, Kuwabara S
  • Journal Title: J Neurol Volume: 259(8) Pages: 1600-5
• [Journal Article] Seroconversion of anti-aquaporin-4 antibody in NMO spectrum disorder : a case report (2012)
  • Author(s): Mori M, Kawaguchi N, Uzawa A, Nemoto Y, Masuda S, Kuwabara S
  • Journal Title: J Neurol Volume: 259(5) Pages: 980-1
• [Presentation] Peptide array法によるAQP4上のimmunogenic site同定の試み (2014)
  • Author(s): 森雅裕、鵜沢顕之、増田冴子、武藤真弓、内田智彦、桑原聡
  • Organizer: 免疫性神経疾患に関する調査研究班 平成23年度
  • Place of Presentation: 東京
  • Year and Date: 2014-01-25
• [Presentation] Peptide array法を用いたNMO患者血清中抗AQP4抗体のAQP4上認識抗原の解析 (2013)
  • Author(s): 森雅裕、鵜沢顕之、増田冴子、武藤真弓、内田智彦、桑原聡
  • Organizer: 第24回日本神経免疫学会学術集会
  • Place of Presentation: 軽井沢(長野)
  • Year and Date: 2013-09-20
• [Presentation] Peptide array analysis for detection of immunogenic site on aquaporin-4 in neuromyelitis optica (2012)
  • Author(s): Mori M, Uzawa A, Masuda S, Muto M, Kuwabara S
  • Organizer: 13th Asian & Oceanian Congress of Neurology (AOCN 2012)
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2012-06-07
• [Presentation] Peptide array analysis for detection of immunogenic site on aquaporin-4 in neuromyelitis optica. (2012)
  • Author(s): 第13回アジアオセアニア神経学会議
  • Organizer: アジアオセアニア神経学会
  • Place of Presentation: メルボルン（オーストラリア）
• [Presentation] Peptide array法によるAQP4上のimmunogenic site同定の試み
  • Author(s): 森 雅裕、鵜沢 顕之、増田 冴子、武藤 真弓、桑原 聡
  • Organizer: 厚生労働省「免疫性神経疾患に関する調査研究班 平成２３年度班会議」
  • Place of Presentation: 東京都都市センターホテル