The effect of NMO-IgG and complement against primary human astrocytes in culture.

• Project/Area Number: 24890017
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Tohoku University
• Principal Investigator: NISHIYAMA Shuhei 東北大学, 大学病院, 医員 (60636017)
• Project Period (FY): 2012-08-31 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 視神経脊髄炎 / アストロサイト / 補体介在性障害 / 補体非介在性障害 / 補体介在性傷害 / 補体非介在性傷害

Research Abstract

Purified IgG derived from anti-Aquaporin 4(AQP4) antibody positive patients(NMO-IgG) itself caused AQP4 cluster on astrocytic membrane following endocytosis. NMO-IgG also caused reversible morphological changes like shrinking of foot processes and adhesion ability. NMO-IgG with human complements irreversibly damage the cells in a short time, suggesting a unique AQP4 antibody-mediated astrocytopathy in NMO.
Complement is involved in the pathogenesis of NMO, and the worn-out of complement regulatory proteins like CD55 or CD59 on the membrane accelerate astrocytic cytotoxicity. The controlling of complement or complement regulatory proteins may be a new therapeutic target in NMO.

Research Products

• [Journal Article] 視神経脊髄炎(NMO)におけるアストロサイトの役割 (2013)
  • Author(s): 西山修平、三須建郎、中島一郎、藤原一男
  • Journal Title: 神経内科 Volume: 79(2) Pages: 257-61
• [Journal Article] 視神経脊髄炎（NMO）におけるアストロサイトの役割 (2013)
  • Author(s): 西山修平、三須建郎、中島一郎、藤原一男
  • Journal Title: 神経内科 Volume: 第79巻第2号 Pages: 257-261
• [Presentation] 炎症性脱髄性疾患の診断・予後における髄液中GFAP濃度有用性の多施設横断的検討 (2013)
  • Author(s): 西山修平、三須建郎、清水優子、横山和正、景山卓、高井良樹、高野里菜、高橋利幸、藤盛寿一、佐藤滋、中島一郎、糸山泰人、藤原一男、青木正志
  • Organizer: 第25回日本神経免疫学会学術集会
  • Place of Presentation: 下関
• [Presentation] A multicentric cross-sectional study of the usefulness of CSF-GFAP in the diagnosis and the prognosis of inflammatory demyelinating diseases (2013)
  • Author(s): S. Nishiyama, T. Misu, Y. Simizu, K. Yokoyama, T. Kageyama, Y. Takai, R. Takano, T. Takahashi, J. Fujimori, S. Sato, I. Nakashima, Y. Itoyama, K. Fujihara, M. Aoki
  • Organizer: PACTRIMS 2013
  • Place of Presentation: 京都
• [Presentation] A multicentric cross-sectional study of the usefulness of CSF-GFAP in the diagnosis and the prognosis of inflammatory demyelinating diseases (2013)
  • Author(s): S. Nishiyama, T. Misu, Y. Simizu, K. Yokoyama, T. Kageyama, Y. Takai, R. Takano, T. Takahashi, J. Fujimori, S. Sato, I. Nakashima, Y. Itoyama, K. Fujihara, M. Aoki
  • Organizer: 29th ECTRIMS
  • Place of Presentation: デンマーク・コペンハーゲン
• [Presentation] 炎症性脱髄性疾患の診断・予後における髄液中GFAP濃度有用性の多施設横断的検討 (2013)
  • Author(s): 西山修平、三須建郎、清水優子、横山和正、景山卓、高井良樹、高野里菜、高橋利幸、藤盛寿一、佐藤滋、中島一郎、糸山泰人、藤原一男、青木正志
  • Organizer: 第54回日本神経学会
  • Place of Presentation: 東京
• [Presentation] 炎症性脱髄性疾患の診断・予後における脳脊髄液中GFAP 濃度有用性の多施設横断的検討 (2013)
  • Author(s): 西山修平、三須建郎、清水優子、横山和正、景山卓、高井良樹、高野里菜、高橋利幸、藤盛寿一、佐藤滋、中島一郎、糸山泰人、藤原一男、青木正志
  • Organizer: 第54回日本神経学会
  • Place of Presentation: 東京国際フォーラム
• [Presentation] A multicentric cross-sectional study of the usefulness of cerebrospinal fluid-glial fibrillary acidic protein (CSF-GFAP) in the diagnosis and prognosis of inflammatory demyelinating diseases (2013)
  • Author(s): S. Nishiyama, T. Misu, Y. Simizu, K. Yokoyama, T. Kageyama, Y. Takai, R. Takano, T. Takahashi, J. Fujimori, S. Sato, I. Nakashima, Y. Itoyama, K. Fujihara, M. Aoki
  • Organizer: 29th ECTRIMS
  • Place of Presentation: デンマーク・コペンハーゲン
• [Presentation] A multicenter, cross-sectional study of the usefulness of CSF-GFAP in the diagnosis and the prognosis of inflammatory CNS diseases. (2013)
  • Author(s): S. Nishiyama, T. Misu, Y. Simizu, K. Yokoyama, T. Kageyama, Y. Takai, R. Takano, T. Takahashi, J. Fujimori, S. Sato, I. Nakashima, Y. Itoyama, K. Fujihara, M. Aoki
  • Organizer: PACTRIMS 2013
  • Place of Presentation: 京都
• [Presentation] 炎症性脱髄性疾患の診断・予後における脳脊髄液中GFAP 濃度有用性の多施設横断的検討 (2013)
  • Author(s): 西山修平、三須建郎、清水優子、横山和正、景山卓、高井良樹、高野里菜、高橋利幸、藤盛寿一、佐藤滋、中島一郎、糸山泰人、藤原一男、青木正志
  • Organizer: 第25回日本神経免疫学会学術集会
  • Place of Presentation: 下関
• [Remarks] 研究内容
  • URL: http://www.ms.med.tohoku.ac.jp/research.html