Elucidating pathomechanisms of seropositive CIDP

• Project/Area Number: 18K15454
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Kyushu University
• Principal Investigator: Hidenori Ogata 九州大学, 大学病院, 助教 (90778838)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: Neurofascin 155 / ランビエ絞輪 / IgG4 / 慢性炎症性脱髄性多発神経炎 / Contactin-1 / 自己抗体 / ニューロパチー / neurofascin 155 / CIDP / contactin-1 / caspr-1 / 慢性炎症性脱髄性多発ニューロパチー / contactin 1 / Caspr-1 / 神経免疫

Outline of Final Research Achievements

Autoantibodies against paranodal proteins, such as neurofascin 155 (NF155) and contactin-1 (CNTN1), have been reported in subsets of chronic inflammatory demyelinating polyneuropathy (CIDP). Through the research, we identified one anti-CNTN1 antibody-positive CIDP patient, who concurrently had membranous nephropathy. We also demonstrated strong associations with human leukocyte antigen (HLA), particularly HLA class II alleles, in IgG4 anti-NF155 antibody-positive CIDP. Then we showed that intrathecal upregulation of type 2 helper T cell cytokines is characteristic of IgG4 anti-NF155 antibody-positive CIDP, while type 1 helper T cell cytokines are increased in CIDP regardless of the presence or absence of anti-NF155 antibodies.

Academic Significance and Societal Importance of the Research Achievements

抗CNTN1抗体陽性CIDPの存在は、蛋白間相互作用によりCIDPを発症するという仮説を支持するものである。今回同定した抗CNTN1抗体陽性CIDP症例は同時に膜性腎症を合併しており、CIDPおよび膜性腎症の発症機序の共通点を見出す上で非常に重要である。また、本研究を通してこれまでにない規模でIgG4抗NF155抗体陽性CIDPの免疫遺伝学的な背景を明らかにすることができた。Th2およびその関連サイトカインは今後、治療標的と成り得る。

Research Products

• [Journal Article] Unique HLA haplotype associations in IgG4 anti-neurofascin 155 antibody-positive chronic inflammatory demyelinating polyneuropathy (2020)
  • Author(s): Ogata H, Isobe N, Zhang X, Yamasaki R, Fujii T, Machida A, Morimoto N, Kaida K, Masuda T, Ando Y, Kuwahara M, Kusunoki S, Nakamura Y, Matsushita T, Kira J.
  • Journal Title: Journal of Neuroimmunology Volume: 339 Pages: 577139-577139
  • DOI: 10.1016/j.jneuroim.2019.577139
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Anti‐nodal/paranodal antibodies in human demyelinating disorders (2020)
  • Author(s): Ogata Hidenori
  • Journal Title: Clinical and Experimental Neuroimmunology Volume: 11 Issue: S1 Pages: 41-47
  • DOI: 10.1111/cen3.12567
  • Open Access
• [Journal Article] Anti-neurofascin autoantibody and demyelination (2019)
  • Author(s): Kira Jun-ichi、Yamasaki Ryo、Ogata Hidenori
  • Journal Title: Neurochemistry International Volume: 130 Pages: 104360-104360
  • DOI: 10.1016/j.neuint.2018.12.011
  • Peer Reviewed
• [Journal Article] Intrathecal cytokine profile in neuropathy with anti‐neurofascin 155 antibody (2019)
  • Author(s): Ogata H, Zhang X, Yamasaki R, Fujii T, Machida A, Morimoto N, Kaida K, Masuda T, Ando Y, Kuwahara M, Kusunoki S, Nakamura Y, Matsushita T, Isobe N, Kira J.
  • Journal Title: Annals of Clinical and Translational Neurology Volume: 6 Issue: 11 Pages: 2304-2316
  • DOI: 10.1002/acn3.50931
  • Peer Reviewed / Open Access
• [Journal Article] Simultaneous MR neurography and apparent T2 mapping in brachial plexus: Evaluation of patients with chronic inflammatory demyelinating polyradiculoneuropathy. (2019)
  • Author(s): Hiwatashi A, Togao O, Yamashita K, Kikuchi K, Momosaka D, Nakatake H, Yamasaki R, Ogata H, Yoneyama M, Kira JI, Honda H.
  • Journal Title: Magn Reson Imaging Volume: 55 Pages: 112-117
  • DOI: 10.1016/j.mri.2018.09.025
  • Peer Reviewed
• [Journal Article] Chronic Inflammatory Demyelinating Polyneuropathy With Concurrent Membranous Nephropathy: An Anti-paranode and Podocyte Protein Antibody Study and Literature Survey (2018)
  • Author(s): Yu Hashimoto, Hidenori Ogata, Ryo Yamasaki, Takakazu Sasaguri, Senri Ko, Kenichiro Yamashita, Zhang Xu, Takuya Matsushita, Takahisa Tateishi, Shin'ichi Akiyama, Shoichi Maruyama, Akifumi Yamamoto, Jun-ichi Kira
  • Journal Title: Frontiers in Neurology Volume: 9 Pages: 997-997
  • DOI: 10.3389/fneur.2018.00997
  • Peer Reviewed / Open Access
• [Journal Article] Lumbar plexus in patients with chronic inflammatory demyelinating polyradiculoneuropathy: evaluation with simultaneous T2 mapping and neurography method with SHINKEI. (2018)
  • Author(s): Hiwatashi A, Togao O, Yamashita K, Kikuchi K, Momosaka D, Nakatake H, Yamasaki R, Ogata H, Yoneyama M, Kira JI, Honda H.
  • Journal Title: Br J Radiol Volume: 91 Issue: 1092 Pages: 20180501-20180501
  • DOI: 10.1259/bjr.20180501
  • Peer Reviewed
• [Journal Article] 抗neurofascin 155抗体陽性慢性炎症性脱髄性多発神経炎 (2018)
  • Author(s): 緒方 英紀, 山崎 亮
  • Journal Title: 末梢神経 Volume: 29 Pages: 9-16
• [Presentation] 点滴用免疫グロブリンより皮下注用免疫グロブリンの定期投与に移行した慢性炎症性脱髄性多発神経炎の一例 (2019)
  • Author(s): 緒方 英紀, 山﨑 亮, 吉良 潤一
  • Organizer: 第7回日本難病医療ネットワーク学会学術集会
• [Presentation] 自己抗体陽性CIDP (2019)
  • Author(s): 緒方 英紀
  • Organizer: 第31回日本神経免疫学会学術集会
  • Invited
• [Presentation] 抗neurofascin 155抗体関連ニューロパチー全国調査結果 (2019)
  • Author(s): 緒方 英紀, 山﨑 亮, 磯部 紀子, 角谷 真人, 海田 賢一, 松井 真, 桑原 聡, 楠 進, 吉良 潤一
  • Organizer: 第31回日本神経免疫学会学術集会
• [Presentation] 抗neurofascin 155抗体陽性CIDPにおける眼窩内脳神経肥厚についての検討 (2019)
  • Author(s): 緒方 英紀, 山﨑 亮, 吉良 潤一
  • Organizer: 第30回日本末梢神経学会学術集会
• [Presentation] 抗neurofascin 155抗体陽性慢性炎症性脱髄性多発神経炎 (2019)
  • Author(s): 緒方 英紀, 山﨑 亮, 吉良 潤一
  • Organizer: 第30回日本末梢神経学会学術集会
  • Invited
• [Presentation] 「自己抗体陽性」CIDP (2019)
  • Author(s): 緒方 英紀
  • Organizer: 第60回日本神経学会学術大会
  • Invited
• [Presentation] Autoantibodies against nodes of Ranvier and paranodes in CIDP (2019)
  • Author(s): Ogata H, Yamasaki R, Kira JI
  • Organizer: 60th Annual Meeting of The Japanese Society of Neurology
  • Invited
• [Presentation] The first nationwide survey results of IgG4 anti-neurofascin155 (NF155) antibody-positive neuropathy (2019)
  • Author(s): Ogata H, Yamasaki R, Kadoya M, Kaida K, Matsui M, Kuwabara S, Kusunoki S, Isobe N, Kira JI
  • Organizer: 60th Annual Meeting of The Japanese Society of Neurology
  • Invited
• [Presentation] CSF cytokine profile and HLA haplotype in IgG4 anti-neurofascin 155 (NF155) antibody-positive CIDP (2019)
  • Author(s): Yamasaki R, Ogata H, Zhang X, Machida A, Morimoto N, Kaida K, Masuda T, Ando Y, Kuwahara M, Kusunoki S, Kira JI
  • Organizer: 60th Annual Meeting of The Japanese Society of Neurology
• [Presentation] Diagnostic values of the criteria for anti-neurofascin 155 antibody-associated neuropathy (2018)
  • Author(s): Ogata Hidenori, Ryo Yamasaki, Takuya Matsushita, Masato Kadoya, Kenichi Kaida, Makoto Matsui, Satoshi Kuwabara, Susumu Kusunoki, Jun-ichi Kira
  • Organizer: 第59回日本神経学会学術大会
• [Presentation] 抗Neurofascin 155 抗体陽性CIDPの分子生物的基盤と臨床像 (2018)
  • Author(s): 緒方英紀，山﨑亮，吉良潤一
  • Organizer: 第59回日本神経学会学術大会
• [Presentation] 抗NF155抗体陽性CIDPを効率よく検出する指標の同定：暫定診断基準案に基づいた全国調査による解析結果 (2018)
  • Author(s): 緒方英紀，山﨑亮，松下拓也，海田賢一，松井真，桑原聡，楠進，吉良潤一
  • Organizer: 第29回日本末梢神経学会学術集会
• [Presentation] 自己抗体陽性CIDPの臨床像および病態機序 (2018)
  • Author(s): 緒方英紀，山﨑亮，吉良潤一
  • Organizer: 第29回日本末梢神経学会学術集会
• [Presentation] 抗neurofascin155抗体陽性CIDPにおける免疫遺伝学的背景因子と髄液サイトカインプロフィール (2018)
  • Author(s): 緒方英紀，山﨑亮，町田明，森本展年，海田賢一，増田曜章，安東由喜雄，桑原基，楠進，吉良潤一
  • Organizer: 第30回日本神経免疫学会学術集会
• [Presentation] A combined immunogenetic and cerebrospinal fluid cytokine study in anti-neurofascin155 antibody-positive neuropathy (2018)
  • Author(s): Hidenori Ogata, Zhang Xu, Ryo Yamasaki, Akira Machida, Nobutoshi Morimoto, Kenichi Kaida, Teruaki Masuda, Yukio Ando, Motoi Kuwahara, Susumu Kusunoki, Jun-ichi Kira
  • Organizer: American Neurological Association Annual Meeting 2018
• [Presentation] 抗neurofascin155抗体陽性CIDPにおける免疫遺伝学的背景因子とT細胞免疫の関与 (2018)
  • Author(s): 緒方英紀，山﨑亮，張旭，町田明，森本展年，海田賢一，増田曜章，安東由喜雄，桑原基，楠進，吉良潤一
  • Organizer: 第36回日本神経治療学会学術集会
• [Presentation] GBS/CIDPの自己抗体（蛋白抗原） (2018)
  • Author(s): 緒方 英紀，山﨑 亮，吉良 潤一
  • Organizer: 第36回日本神経治療学会学術集会