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Comprehensive search of autoantibies in neuroimmunological disorders using a novel hybrid SEREX-FACS method

Research Project

Project/Area Number 18K07387
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionChiba University

Principal Investigator

Masahiro Mori  千葉大学, 大学院医学研究院, 准教授 (70345023)

Co-Investigator(Kenkyū-buntansha) 鵜沢 顕之  千葉大学, 医学部附属病院, 助教 (10533317)
八木 良二  千葉大学, 大学院医学研究院, 特任准教授 (20392152)
日和佐 隆樹  千葉大学, 大学院医学研究院, 特任准教授 (30260251)
星野 忠次  千葉大学, 大学院薬学研究院, 准教授 (90257220)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords視神経脊髄炎 / 神経免疫疾患 / 自己抗体 / フローサイトメトリー / SEREX / SEREX法 / FACS / 抗体 / 自己免疫
Outline of Final Research Achievements

We have obtained sera from double seronegative (dSN) neuromyelitis optica patients without anti-aquaporin-4 antibody or anti-myelin oligodendrocyte glycoprotein antibody, and a cDNA library (plasmid DNA) constructed from human brain, which were transferred into HEK293 cells. Then, the transformed cells were reacted with sera from the dSN NMO patients. The reacted cells were collected by a Cell Sorter. Plasmid DNA was extracted from the collected cells, and amplified by PCR. Nucleotide sequences were determined with PCR-amplified DNA using an automated sequencer. After the homology screening of the identified genes within the public sequence database, and we succeded in identification of two possible antigen genes.

Academic Significance and Societal Importance of the Research Achievements

今回、我々はSEREX法とFACS法を融合させた、世界で初めての新手法を編みだし、自己免疫が関与する神経難病であり、既存の抗体が陰性で原因が未解明である視神経脊髄炎患者血清を用いた検討を行った。結果、新規自己抗原候補のタンパクをコードする遺伝子の同定に成功した。それらが真の自己抗原か、さらなる検討が必要であるが、この方法が実際に施行でき、新規自己抗原が検出できる可能性を明確に示した点で学術的な意義は大きく、さらにこの方法が他の原因不明の多くの自己免疫疾患に応用できる可能性を秘めており、それらの疾患の治療に結びつきうる点でも意義は大きいと考える。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (16 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (15 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 14 results,  Open Access: 1 results)

  • [Int'l Joint Research] シャリテ医科大学(ドイツ)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Novel serum autoantibodies against ß-actin (ACTB) in amyotrophic lateral sclerosis.2021

    • Author(s)
      Sugimoto K, Mori M, Liu J, Shibuya K, Isose S, Koide M, Hiwasa T, Kuwabara S.
    • Journal Title

      Amyotroph Lateral Scler Frontotemporal Degener.

      Volume: 1 Issue: 5-6 Pages: 1-7

    • DOI

      10.1080/21678421.2021.1885448

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-MOG antibody-associated disorders: differences in clinical profiles and prognosis in Japan and Germany.2020

    • Author(s)
      Liu J, Mori M, Zimmermann H, Brandt A, Havla J, Tanaka S, Sugimoto K, Oji S, Uzawa A, Asseyer S, Cooper G, Jarius S, Bellmann-Strobl J, Ruprecht K, Siebert N, Masuda H, Uchida T, Ohtani R, Nomura K, Meinl E, Kuempfel T, Paul F, Kuwabara S.
    • Journal Title

      J Neurol Neurosurg Psychiatry.

      Volume: -- Issue: 4 Pages: 377-383

    • DOI

      10.1136/jnnp-2020-324422

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Serum anti-LRPAP1 is a common biomarker for digestive organ cancers and atherosclerotic diseases.2020

    • Author(s)
      Sumazaki M, Shimada H, Ito M, Shiratori F, Kobayashi E, Yoshida Y, Adachi A, Matsutani T, Iwadate Y, Mine S, Machida T, Kamitsukasa I, Mori M, Sugimoto K, Uzawa A, Kuwabara S, et al.
    • Journal Title

      Cancer Sci.

      Volume: 11 Pages: 4453-4464

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peroxiredoxins are involved in the pathogenesis of multiple sclerosis and neuromyelitis optica spectrum disorder.2020

    • Author(s)
      Uzawa A, Mori M, Masuda H, Ohtani R, Uchida T, Aoki R, Kuwabara S.
    • Journal Title

      Clin Exp Immunol.

      Volume: 202 Issue: 2 Pages: 239-248

    • DOI

      10.1111/cei.13487

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Safety and efficacy of rituximab in neuromyelitis optica spectrum disorders (RIN-1 study): a multicentre, randomised, double-blind, placebo-controlled trial.2020

    • Author(s)
      Tahara M, Oeda T, Okada K, Kiriyama T, Ochi K, Maruyama H, Fukaura H, Nomura K, Shimizu Y, Mori M, Nakashima I, Misu T, Umemura A, Yamamoto K, Sawada H.
    • Journal Title

      Lancet Neurol.

      Volume: 19 Issue: 4 Pages: 298-306

    • DOI

      10.1016/s1474-4422(20)30066-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Peripheral blood helper T cell profiles and their clinical relevance in MOG-IgG-associated and AQP4-IgG-associated disorders and MS.2020

    • Author(s)
      Liu J, Mori M, Sugimoto K, Uzawa A, Masuda H, Uchida T, Ohtani R, Kuwabara S.
    • Journal Title

      J Neurol Neurosurg Psychiatry.

      Volume: 91 Issue: 2 Pages: 132-139

    • DOI

      10.1136/jnnp-2019-321988

    • Related Report
      2019 Research-status Report
  • [Journal Article] The accuracy of flow cytometric cell-based assay to detect anti-myelin oligodendrocyte glycoprotein (MOG) antibodies determining the optimal method for positivity judgement.2019

    • Author(s)
      Sugimoto K, Mori M, Liu J, Tanaka S, Kaneko K, Oji S, Takahashi T, Uzawa A, Uchida T, Masuda H, Ohtani R, Nomura K, Hiwasa T, Kuwabara S.
    • Journal Title

      J Neuroimmunol.

      Volume: 336 Pages: 577021-577021

    • DOI

      10.1016/j.jneuroim.2019.577021

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diagnosis and Treatment of NMO Spectrum Disorder and MOG-Encephalomyelitis2018

    • Author(s)
      Borisow Nadja、Mori Masahiro、Kuwabara Satoshi、Scheel Michael、Paul Friedemann
    • Journal Title

      Frontiers in Neurology

      Volume: 9 Pages: 888-888

    • DOI

      10.3389/fneur.2018.00888

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Novel autoantibodies against the proteasome subunit PSMA7 in amyotrophic lateral sclerosis2018

    • Author(s)
      Sugimoto Kazuo、Hiwasa Takaki、Shibuya Kazutomo、Hirano Shigeki、Beppu Minako、Isose Sagiri、Arai Kimihito、Takiguchi Masaki、Kuwabara Satoshi、Mori Masahiro
    • Journal Title

      Journal of Neuroimmunology

      Volume: 325 Pages: 54-60

    • DOI

      10.1016/j.jneuroim.2018.09.013

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Atypical chronic inflammatory demyelinating polyneuropathies2018

    • Author(s)
      Kuwabara Satoshi、Misawa Sonoko、Mori Masahiro
    • Journal Title

      Journal of Neurology, Neurosurgery & Psychiatry

      Volume: 90 Issue: 2 Pages: 121-121

    • DOI

      10.1136/jnnp-2018-319411

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] MOG antibody disorders and AQP4 antibody NMO spectrum disorders share a common immunopathogenesis2018

    • Author(s)
      Uzawa Akiyuki、Mori Masahiro、Kuwabara Satoshi
    • Journal Title

      Journal of Neurology, Neurosurgery & Psychiatry

      Volume: 89 Issue: 9 Pages: 900-900

    • DOI

      10.1136/jnnp-2018-318231

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intravenous immunoglobulin for maintenance treatment of multifocal motor neuropathy: A multi-center, open-label, 52-week phase 3 trial2018

    • Author(s)
      Kuwabara Satoshi、Misawa Sonoko、Mori Masahiro、Iwai Yuta、Ochi Kazuhide、Suzuki Hidekazu、Nodera Hiroyuki、Tamaoka Akira、Iijima Masahiro、Toda Tatsushi、Yoshikawa Hiroo、Kanda Takashi、Sakamoto Ko、Kusunoki Susumu、Sobue Gen、Kaji Ryuji、on behalf of the Glovenin-I MMN Study Group
    • Journal Title

      Journal of the Peripheral Nervous System

      Volume: 23 Issue: 2 Pages: 115-119

    • DOI

      10.1111/jns.12268

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serum anti-JCV antibody indexes in Japanese patients with multiple sclerosis: elevations along with fingolimod treatment duration2018

    • Author(s)
      Aoyama Shinji、Mori Masahiro、Uzawa Akiyuki、Uchida Tomohiko、Masuda Hiroki、Ohtani Ryohei、Kuwabara Satoshi
    • Journal Title

      J Neurol

      Volume: in press Issue: 5 Pages: 1145-1150

    • DOI

      10.1007/s00415-018-8813-z

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Recombinant thrombomodulin ameliorates experimental autoimmune encephalomyelitis by suppressing HMGB1 and inflammatory cytokines2018

    • Author(s)
      Uzawa Akiyuki、Mori Masahiro、Masuda Hiroki、Ohtani Ryohei、Uchida Tomohiko、Kuwabara Satoshi
    • Journal Title

      Clin Exp Immunol

      Volume: in press Issue: 1 Pages: 47-54

    • DOI

      10.1111/cei.13123

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Worldwide prevalence of neuromyelitis optica spectrum disorders2018

    • Author(s)
      Mori Masahiro、Kuwabara Satoshi、Paul Friedemann
    • Journal Title

      Journal of Neurology, Neurosurgery & Psychiatry

      Volume: 89 Issue: 6 Pages: 555-556

    • DOI

      10.1136/jnnp-2017-317566

    • Related Report
      2018 Research-status Report
    • Peer Reviewed

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Published: 2018-04-23   Modified: 2022-01-27  

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