Role of IL-17 producing T cells in opticospinal multiple sclerosis

2008 Fiscal Year Final Research Report

• Project/Area Number: 18390261
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Kyushu University
• Principal Investigator: KIRA Jun-ichi Kyushu University, 大学院・医学研究院, 教授 (40183305)
• Co-Investigator(Kenkyū-buntansha): MINOHARA Motozumi 九州大学, 大学病院, 講師 (70398113) ; KAWAMURA Nobutoshi 九州大学, 医学研究院, 学術研究員 (00432930)
• Project Period (FY): 2006 – 2008
• Keywords: 多発性硬化症 / 視神経脊髄型 / IL-17 / 自己反応性T細胞 / 抗AQP4抗体

Research Abstract

日本人の視神経脊髄型多発性硬化症(OSMS)と再発寛解型neuromyelitis optica(NMO)はその病像が類似点が多い。抗aquaporin-4(AQP4)抗体の有無により日本人MS患者を再分類し、細胞内サイトカイン、並びに髄液中のサイトカイン・ケモカインを測定した結果、抗AQP4抗体陽性患者では脳脊髄液中のCD4陽性T細胞内サイトカインではIL-4産生細胞が上昇し、一方で末梢血では抗体陰性OSMSにおいてIFN-γ^+IL-4^-細胞の比率が高くTh1シフトの傾向を認め、脳脊髄液中では、OSMSではIL-17、IL-8、G-CSFの濃度が上昇している点など、抗AQP4抗体陽性例と、陰性群の中でもOSMSとCMSではそれぞれ異なる炎症性機序が働いていることが示唆された。今後さらに責任自己抗原の違いや拘束分子の相違など検討を進めることで病態を把握し、各病型に特異的な治療法の確立に努めたい。

Research Products

• [Journal Article] Association of the HLA-DRB1 alleles with characteristic MRI features of Asian multiple sclerosis (2009)
  • Author(s): Matsuoka T, Matsushita T, Osoegawa M, Kawano Y, Minohara M, Mihara F, Nishimura Y, Ohyagi Y, Kira J
  • Journal Title: Multiple Sclerosis 14 Pages: 1181-1190
  • Peer Reviewed
• [Journal Article] Increase of CD4^+ TNFα^+ IL-2^-T cells in cerebrospinal fluid of multiple sclerosis patients (2009)
  • Author(s): Shi N, Kawano Y, Matsuoka T, Mei F-J, Ishizu T, Ohyagi Y, Kira J
  • Journal Title: Multiple Sclerosis 15 Pages: 120-123
  • Peer Reviewed
• [Journal Article] Angiotensin-converting anzyme(ACE)and ACE2 levels in the cerebrospinal fluid of patients with multiple sclerosis (2009)
  • Author(s): Kawajiri M, Mogi M, Higaki N, Matsuoka T, Ohyagi Y, Tsukada K, Kahara K, Horiuchi M, Miki T, Kira J
  • Journal Title: Multiple Sclerosis 15 Pages: 262-265
  • Peer Reviewed
• [Journal Article] Temporal changes and geographical differences in multiple sclerosis phenotypes in Japanese : nationwide survey results over 30 years (2009)
  • Author(s): Osoegawa M, Kira J, Fukazawa K, Kikuchi S, Kohriyama T, Sobue G, Yamamura T, Itoyama Y, Saida T, Sakata K, Ochi H, Matsuoka T
  • Journal Title: Multiple Sclerosis(Equal contribution) 15 Pages: 159-173
  • Peer Reviewed
• [Journal Article] Hypercomplementemia at relapse in patients with anti-aquaporin-4 antibody (2009)
  • Author(s): Doi H, Matsushita T, Isobe N, Matsuoka T, Minohara M, Ochi H, Kira J
  • Journal Title: Multiple Sclerosis 15 Pages: 304-310
  • Peer Reviewed
• [Journal Article] Association of the HLADPB1*0501 allele with anti-aquaporin-4 antibody positivity in Japanese patients with idiopathic central nervous system demyelinating disorders (2009)
  • Author(s): Matsushita T, Matsuoka T, Isobe N, Kawamura Y, Minohara M, Shi N, Nishimura Y, Ochi H, Kira J
  • Journal Title: Tissue Antigens 72 Pages: 171-176
  • Peer Reviewed
• [Journal Article] Heterogeneity and continuum of multiple sclerosis phenotypes in Japanese according to the results of the fourth nationwide survey(Equal contribution) (2009)
  • Author(s): Ishizu T, Kira J, Osoegawa M, Fukazawa T, Kikuchi S, Fujihara K, Matsui M, Kohriyama T, Sobue G, Yamamura T, Itoyama Y, Saida T, Sakata K
  • Journal Title: J Neurol Sci 280 Pages: 22-28
  • Peer Reviewed
• [Journal Article] Anterior periventricular linear lesions in optic-spinal multiple sclerosis : a combined neuroimaging and neuropathological study (2008)
  • Author(s): Matsushita T, Matsuoka T, Ishizu T, Kikuchi H, Osoegawa M, Kawano Y, Mihara F, Ohyagi Y, Kira J
  • Journal Title: Multiple Sclerosis 14 Pages: 343-53
  • Peer Reviewed
• [Journal Article] Heterogeneity and continuum of multiple sclerosis in Japanese according to magnetic resonance imaging findings (2008)
  • Author(s): Matsuoka T, Matsushita T, Osoegawa M, Ochi H, Kawano Y, Mihara F, Ohyagi Y, Kira J
  • Journal Title: J Neurol Sci 266 Pages: 115-25
  • Peer Reviewed
• [Journal Article] Distinct CSF cytokine/chemokine profiles in atopic myelitis and other causes of myelitis (2008)
  • Author(s): Tanaka M, Matsushita T, Tateishi T, Ochi H, Kawano Y, Mei F-J, Minohara M, Murai H, Kira J
  • Journal Title: Neurology 71 Pages: 974-981
  • Peer Reviewed
• [Journal Article] Helicobacter pylori is a potential protective factor against conventional type multiple sclerosis in the Japanese population (2007)
  • Author(s): Li W, Minohara M, Su JJ, Matsuoka T, Osoegawa M, Ishizu T, Kira J
  • Journal Title: J Neuroimmunol 184 Pages: 227-231
  • Peer Reviewed
• [Journal Article] Heterogeneity of aquaporin-4 autoimmunity and spinal cord lesions in multiple sclerosis in Japanese (2007)
  • Author(s): Matsuoka T, Matsushita T, Kawano Y, Osoegawa M, Ochi H, Ishizu T, Minohara M, Kikuchi H, Mihara F, Ohyagi Y, Kira J
  • Journal Title: Brain 130 Pages: 1206-1223
  • Peer Reviewed
• [Journal Article] Upregulation of vascular growth factors in multiple sclerosis : correlation with MRI findings (2006)
  • Author(s): Su J-J, Osoegawa M, Minohara M, Tanaka M, Ishizu T, Mihara F, Taniwaki T, Kira J
  • Journal Title: J Neurol Sci 243 Pages: 21-30
  • Peer Reviewed
• [Journal Article] Long-term favorable response to interferon beta-1b is linked to cytokine deviation toward the Th2 and Tc2 sides in Japanese patients with multiple sclerosis (2006)
  • Author(s): Mei F-J, Osoegawa M, Ochi H, Minohara M, Shi N, Murai H, Ishizu T, Taniwaki T, Kira J
  • Journal Title: J Neurol Sci 246 Pages: 71-77
  • Peer Reviewed
• [Journal Article] Upregulation of myeloperoxidase in patients with opticospinal multiple sclerosis : positive correlation with disease severity (2006)
  • Author(s): Minohara M, Matsuoka T, Li W, Osoegawa M, Ishizu T, Ohyagi Y, Kira J
  • Journal Title: J Neuroimmunol 178 Pages: 156-160
  • Peer Reviewed
• [Journal Article] The selective Rho-kinase inhibitor Fasudil is protective and therapeutic in experimental allergic encephalomyelitis (2006)
  • Author(s): Sun X, Minohara M, Kikuchi S, Ishizu T, Tanaka M, Piao H, Osoegawa M, Ohyagi Y, Shimokawa H, Kira J
  • Journal Title: J Neuroimmunol 180 Pages: 126-134
  • Peer Reviewed
• [Journal Article] Aquaporin-4 autoimmune syndrome and anti-aquaporin-4 antibody-negative optico spinal multiple sclerosis in Japanese
  • Author(s): Matsushita T, Isobe N, Matsuoka T, Shi N, Kawano Y, Wu X-M, Yoshiura T, Nakao Y, Ishizu T, Kira J
  • Journal Title: Multiple Sclerosis (in press)
  • Peer Reviewed
• [Presentation] 末梢免疫担当細胞におけるbrain-derivedneurotrophic factor (BDNF)産生能と多発性硬化症(MS)病態との関連 (2009)
  • Author(s): 吉村怜, ら
  • Organizer: 第21回日本神経免疫学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-12
• [Presentation] 多発性硬化症および抗アクアポリン4抗体陽性症例における補体系の検討 (2009)
  • Author(s): 土井光, ら
  • Organizer: 第21回日本神経免疫学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-12
• [Presentation] 抗aquaporin-4(AQP4)抗体陽性例における細胞内・脳脊髄液中サイトカインの特徴 (2009)
  • Author(s): 松下拓也, ら
  • Organizer: 第21回日本神経免疫学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-12
• [Presentation] CSF and peripheral blood cytokine production profiles and HLA class II alleles in patients with antibody to aquaporin-4 (2008)
  • Author(s): Kira et.al.
  • Organizer: 133rd Annual Meeting of the American Neurological Association
  • Place of Presentation: Salt Lake City, USA
  • Year and Date: 2008-09-21
• [Presentation] Distinct cerebrospinal fluid cytokine/chemokine profiles in opticospinal multiple sclerosis, atopic myelitis and other causes of myelitis (2008)
  • Author(s): Kira J et.al.
  • Organizer: WORLD CONGRESS ON TREATMENT AND RESEARCH IN MULTIPLE SCLEROSIS
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2008-09-17
• [Presentation] Japanese opticospinal form of MS-the real story (2008)
  • Author(s): Kira J.
  • Organizer: International Neuro-Opthalmology Society
  • Place of Presentation: California, USA
  • Year and Date: 2008-06-07
• [Presentation] Neuromyelitis optica (2008)
  • Author(s): Kira J.
  • Organizer: MULTIPLE SCLEROSIS : COMPREHENSIVE APPROACHES TO COMPLEXCHALLENGES 22ND CMSC ANNUAL MEETING
  • Place of Presentation: Denver, USA
  • Year and Date: 2008-05-28
• [Presentation] FACSによる抗native AQP4抗体の高感度検出法の開発 (2008)
  • Author(s): 河野祐治, ら
  • Organizer: 第49回日本神経学会総
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-15
• [Presentation] 抗aquaporin-4(AQP4)抗体価とMRI所見・サイトカインバランス・HLAとの相関 (2008)
  • Author(s): 松下拓也, ら
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-15
• [Presentation] CD4^+TNFα+IL2^-T細胞のMS髄液中での増加 (2008)
  • Author(s): 史楠, ら
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-15
• [Presentation] アクアポリン4と多発性硬化症 : AQP4自己免疫症候群とseronegative OSMS (2008)
  • Author(s): 吉良潤一
  • Organizer: 第20回日本神経免疫学会学術集会
  • Place of Presentation: 新潟
  • Year and Date: 2008-04-17
• [Presentation] 抗aquaporin-4(AQP4)抗体価による多発性硬化症の免疫学的・遺伝学的背景の差異 (2008)
  • Author(s): 河野祐治, ら
  • Organizer: 第20回日本神経免疫学会学術集会
  • Place of Presentation: 新潟
  • Year and Date: 2008-04-17
• [Presentation] 多発性硬化症におけるconformationalにAQP1を認識する抗体の検索 (2008)
  • Author(s): 河村信利, ら
  • Organizer: 第20回日本神経免疫学会学術集会
  • Place of Presentation: 新潟
  • Year and Date: 2008-04-17
• [Presentation] 脊髄炎症性疾患のサイトカイン・ケモカインプロフィール (2008)
  • Author(s): 田中正人, ら
  • Organizer: 第20回日本神経免疫学会学術集会
  • Place of Presentation: 新潟
  • Year and Date: 2008-04-17
• [Presentation] 日本人多発性硬化症におけるMRI所見とHLAクラスII遺伝子多型との相関 (2007)
  • Author(s): 三野原元澄, ら
  • Organizer: 第48回日本神経学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-05-16
• [Presentation] 日本人多発性硬化症の疫学と動向-視神経脊髄型多発性硬化症を中心として- (2006)
  • Author(s): 吉良潤一
  • Organizer: 第47回日本神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 2006-05-11
• [Presentation] 神経免疫疾患のエフェクターアーム (2006)
  • Author(s): 吉良潤一
  • Organizer: 第18回日本神経免疫学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2006-03-02
• [Presentation] 日本人多発性硬化症の自験130例脳・脊髄MRIの特徴と欧米例との差異 (2006)
  • Author(s): 松岡健, ら
  • Organizer: 第18回日本神経免疫学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2006-03-02
• [Presentation] 日本人多発性硬化症における血清myeloperoxidase値の上昇 (2006)
  • Author(s): 三野原元澄, ら
  • Organizer: 第18回日本神経免疫学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2006-03-02
• [Book] 脱髄性疾患.最新神経内科学(荒木淑朗(編)) (2008)
  • Author(s): 吉良潤一
  • Total Pages: 655-670
  • Publisher: 金芳堂
• [Book] わが国における多発性硬化症の臨床像・診断・治療の変遷.多発性硬化症の診断と治療(吉良潤一(編)) (2008)
  • Author(s): 吉良潤一
  • Total Pages: 3-8
  • Publisher: 新興医学出版
• [Book] 多発性硬化症の治療の進め方.急性憎悪期の治療の進め方.副腎皮質ステロイド薬.多発性硬化症の診断と治療(吉良潤一(編)) (2008)
  • Author(s): 吉良潤一
  • Total Pages: 144-150
  • Publisher: 新興医学出版
• [Book] 多発性硬化症よくわかる病態生理.第8巻「神経疾患」(松尾理(編)) (2007)
  • Author(s): 吉良潤一
  • Total Pages: 124-128
  • Publisher: 日本医事新報社
• [Book] Etiology of multiple sclerosis. WFN Seminars in Clinical Neurology. Edited by Oger J (2006)
  • Author(s): Kira J
  • Total Pages: 1-6
  • Publisher: Al-Aragi A. Demos Medical Pub. Inc. (New York)
• [Book] 多発性硬化症神経疾患最新の治療2006-2008(小林祥泰、水澤英洋(編)) (2006)
  • Author(s): 三野原元澄、吉良潤一
  • Total Pages: 120-4
  • Publisher: 南江堂
• [Book] Aquaporin 4 autoimmunity in multiple sclerosis in Japanese. Ed. by Tabira T, Yamamura T, Kira J. Current Topics in Neuroimmunology (2006)
  • Author(s): Kira J, Matsushita T, Matsuoka T
  • Total Pages: 33-39
  • Publisher: Medimond
• [Remarks]
  • URL: http://www.med.kyushu-u.ac.jp/neuro/