フィッシャー症候群の動物モデル作成と発症機序の解明

2001 Fiscal Year Annual Research Report

• Project/Area Number: 12770323
• Research Institution: Dokkyo Medical University
• Principal Investigator: 結城 伸泰 獨協医科大学, 医学部, 助教授 (60285913)
• Keywords: フィッシャー症候群 / ギラン・バレー症候群 / 分子相同性 / Haemophilus influenzae / Campylobacter jejuni / IgG抗GQ1b抗体 / IgG抗GM1抗体 / 動物モデル

Research Abstract

研究成果:
(1)フィッシャー症侯群患者から実際に分離培養されたC. jejuniからGQ1b様リポ多糖を抽出し、ウサギに感作した。10羽中1羽でIgG抗GQ1b抗体が誘導された。しかしながら、外眼筋麻痺や運動失調は呈さなかった。
(2)フィッシャー症候群の原著症例のうち2例目がH. influenzae肺炎が先行していたことに着目し、血清疫学的に検討した。フィッシャー症候群患者70例、ギラン・バレー症候群患者110例、年齢・性別をマッチさせた他の神経疾患患者62例、正常対照82例の血清抗H. influenzae抗体を調べた。フィッシャー症候群では対照に比して有意にIgM/IgG/IgA抗H. influenzae抗体が高かった。ギラン・バレー症候群では対照群との有意差はなかった。血清学的にH. influenzaeの先行感染が示唆されたフィッシャー症候群5例、ギラン・バレー症候群2例は全例上気道炎症状を前駆症状としていた。b型抗H. influenzae標準株のリポ多糖が(GQlbに類似した)GT1aエピトープを有することを薄層クロマトグラム免疫染色で確認した。
今後の研究の展開に関する計画:
・H. influenzaeがフィッシャー症候群の先行感染因子であることを確立するために症例対照試験を実施する。
抗ガングリオシド抗体測定目的で日本全国より送付されてくるフィッシャー症候群、ギラン・バレー症候群患者の血清を対象とし、各主治医に依頼して同時期に入院している年齢・性別をマッチさせた病院対照血清の収集を開始した。病院対照血清を有する症例は、現時点で、フィッシャー症候群40例、ギラン・バレー症候群130例集まっている。
・フィッシャー症候群患者喀痰からH. influenzaeを分離し、菌体上にGQ1b様リポ多糖が存在することを証明する。
抗ガングリオシド抗体検索の依頼を受けるときに各主治医に菌株分離を依頼してきた。すでにフィッシャー症候群患者から1株、ギラン・バレー症候群患者から2株が分離され、保存されている。ひきつづき菌株数を増やす努力をしている。

Research Products

• [Publications] Yuki N: "Animal model of axonal Guillain-Barre syndrome induced by sensitization with GM1 ganglioside"Ann Neurol. 49. 712-720 (2001)
• [Publications] Yuki N: "Infectious origins of, and molecular mimicry in, Guillain-Barre and Fisher syndromes"Lancet Infect Dis. 1. 29-37 (2001)
• [Publications] Yuki N: "Acute ophthalmoparesis(without ataxia)associated with anti-GQ1b IgG antibody : clinical features"Ophthalmology. 108. 196-200 (2001)
• [Publications] Koga M: "Miller Fisher syndrome and Haemophilus influenzae infection"Neurology. 57. 686-691 (2001)
• [Publications] Odaka M: "Anti-GQ1b IgG antibody syndrome : clinical and immunological range"J Neurol Neurosurg Psychiatry. 70. 50-55 (2001)
• [Publications] Susuki K: "Features of sensory ataxic neuropathy associated with anti-GD1b IgM antibody"J Neuroimmunol. 112. 181-187 (2001)
• [Publications] Susuki K: "Fine specificity of anti-GQ1b IgG and clinical features"J Neurol Sci. 185. 5-9 (2001)
• [Publications] Koga M: "Antecedent symptoms in Guillain-Barre syndrome : an important indicator for clinical and serological subgroups"Acta Neurol Scand. 103. 278-287 (2001)
• [Publications] Koga M: "Range of cross reactivity of anti-GM1 IgG antibody in Guillain-Barre syndrome"J Neurol Neurosurg Psychiatry. 71. 123-124 (2001)
• [Publications] Koga M: "Comparative study of preceding Campylobacter jejuni infection in Guillain-Barre syndrome between Japan and The Netherlands"J Neurol Neurosurg Psychiatry. 70. 693-695 (2001)
• [Publications] Mori M: "Clinical features and prognosis of Miller Fisher syndrome"Neurology. 56. 1104-1106 (2001)
• [Publications] Kuwabara S: "Intravenous immunoglobulin therapy for Guillain-Barre syndrome with IgG anti-GM1 antibody"Muscle Nerve. 24. 54-58 (2001)
• [Publications] Yamashita H: "Polyneuritis cranialis related to anti-GT1a IgG antibody"J Neurol. 248. 65-66 (2001)
• [Publications] Susuki K: "Rapid resolution of nerve conduction blocks after plasmapheresis in Guillain-Barre syndrome associated with anti-GM1b IgG antibody"J Neurol. 248. 148-150 (2001)
• [Publications] Kuwabara S: "Indicators of rapid clinical recovery in Guillain-Barre syndrome"J Neurol Neurosurg Psychiatry. 70. 560-562 (2001)
• [Publications] Tagawa Y: "Parameters for monitoring treatment effects in CIDP with anti-MAG/SGPG IgM antibody"Muscle Nerve. 24. 701-704 (2001)
• [Publications] Yuki N: "Overlapping Guillain-Barre syndrome and Bickerstaff's brainstem encephalitis associated with anti-GQ1b IgG antibody after herpes simplex virus infection"Acta Neurol Scand. 104. 57-60 (2001)
• [Publications] Susuki K: "Guillain-Barre syndrome mimicking botulism"J Neurol. 248. 720-721 (2001)
• [Publications] Pan CL: "Acute sensory ataxic neuropathy associated with monospecific anti-GD1b IaG antibody"Neurology. 57. 1316-1318 (2001)
• [Publications] Nishimoto Y: "Neck stiffness in two children with Guillain-Barre syndrome after Campylobacter jejuni infection"J Neurol. 248. 1104-1105 (2001)
• [Publications] Tagawa Y: "Bickerstaff's brainstem encephalitis associated with shingles"J Neurol. 247. 218-219 (2000)
• [Publications] Kuwabara S: "Isolated absence of F waves and proximal axonal dysfunction in Guillain-Barre syndrome with antiganglioside antibodies"J Neurol Neurosurg Psychiatry. 68. 191-195 (2000)
• [Publications] Yamamoto T: "No cytomegalovirus DNA in sera from patients with anti-MAG/SGPG antibody-associated neuropahy : reply"Ann Neurol. 47. 274-275 (2000)
• [Publications] Yuki N: "Distinctions between critical illness polyneuropathy and axonal Guillain-Barre syndrome : reply"J Neurol Neurosurg Psychiatry. 68. 398 (2000)
• [Publications] Yuki N: "Clinical features and response to treatment in Guillain-Barre syndrome associated with antibodies to GM1b ganglioside"Ann Neurol. 47. 314-321 (2000)
• [Publications] Yuki N: "Bickerstaff's brainstem encephalitis subsequent to Campylobacter jejuni enteritis"J Neurol Neurosurg Psychiatry. 68. 680-681 (2000)
• [Publications] Yuki N: "Current cases in which epitope mimicry is considered as a component cause of autoimmune disease : Guillain-Barre syndrome"Cell Mol Life Sci. 57. 527-533 (2000)
• [Publications] Yuki N: "Ataxic Guillain-Barre syndrome with anti-GQ1b antibody : relation to Miller Fisher syndrome"Neurology. 54. 1851-1853 (2000)
• [Publications] Tagawa Y: "Anti-SGPG antibody in CIDP : nosological position of IgM anti-MAG/SGPG-associated neuropathy"Muscle Nerve. 23. 895-899 (2000)
• [Publications] Odaka M: "Antibodies to GM1(NeuGc)in Guillain-Barre syndrome after ganglioside therapy"J Neurol Sci. 175. 96-106 (2000)
• [Publications] Yuki N: "Ataxic form of Guillain-Barre syndrome associated with anti-GD1b IgG antibody"J Neurol Neurosurg Psychiatry. 69. 136-137 (2000)
• [Publications] Yuki N: "Is Campylobacter lipopolysaccharide bearing a GD3 epitope essential for the pathogenesis of Guillain-Barre syndrome ?"Acta Neurol Scand. 102. 132-134 (2000)
• [Publications] Susuki K: "Unilateral ophthalmoparesis and limb ataxia associated with anti-GQ1b IgG antibody"J Neurol. 247. 652-653 (2000)
• [Publications] Ogawara K: "Axonal Guillain-Barre syndrome : relation to anti-ganglioside antibodie and Campylobacter jejuni infection in Japan"Ann Neurol. 48. 624-631 (2000)
• [Publications] Saito T: "A case of Bickerstaff's brainstem encephalitis mimicking tetanus"J Neurol Neurosurg Psychiatry. 69. 695-696 (2000)
• [Publications] Yuki N: "Guillain-Barre, Fisher, and Bickerstaff syndromes : nature versus well established ideas : reply"J Neurol Neurosurg Psychiatry. 69. 703-704 (2000)
• [Publications] Koga M: "Pain in Miller Fisher syndrome"J Neurol. 247. 720-721 (2000)
• [Publications] Yuki N: "Ataxic Guillain-Barre syndrome with anti-GQ1b antibody : relation to Miller Fisher syndrome : reply"Neurology. 55. 1419-1420 (2000)
• [Publications] Yuki N: "Immunopathogenesis of neurological disorders subsequent to Campylobacter jejuni enteritis"Adv Clin Neurosci. 10. 155-172 (2000)
• [Publications] Koga M: "Pharyngeal-cervical-brachial Guillain-Barre syndrome"Adv Clin Neurosci. 10. 173-186 (2000)
• [Publications] Odaka M: "Bickerstaff's brainstem encephalitis : diagnostic criteria and immunopathogenesis"Adv Clin Neurosci. 10. 207-221 (2000)
• [Publications] 結城伸泰: "難病の最新情報:疫学から臨床・ケアまで"南山堂. 1 (2000)
• [Publications] 結城伸泰: "免疫学辞典(第2版)"東京化学同人. 1 (2001)
• [Publications] 結城伸泰: "免疫学辞典(第3版)"東京化学同人. 1 (2001)