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 年度 実績報告書

• 研究課題/領域番号: 12770323
• 研究機関: 獨協医科大学
• 研究代表者: 結城 伸泰 獨協医科大学, 医学部, 助教授 (60285913)
• キーワード: 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

研究概要

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。

研究成果

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• [文献書誌] Ogawara K: "Axonal Guillain-Barre syndrome : relation to anti-ganglioside antibodie and Campylobacter jejuni infection in Japan"Ann Neurol. 48. 624-631 (2000)
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• [文献書誌] Yuki N: "Guillain-Barre, Fisher, and Bickerstaff syndromes : nature versus well established ideas : reply"J Neurol Neurosurg Psychiatry. 69. 703-704 (2000)
• [文献書誌] Koga M: "Pain in Miller Fisher syndrome"J Neurol. 247. 720-721 (2000)
• [文献書誌] Yuki N: "Ataxic Guillain-Barre syndrome with anti-GQ1b antibody : relation to Miller Fisher syndrome : reply"Neurology. 55. 1419-1420 (2000)
• [文献書誌] Yuki N: "Immunopathogenesis of neurological disorders subsequent to Campylobacter jejuni enteritis"Adv Clin Neurosci. 10. 155-172 (2000)
• [文献書誌] Koga M: "Pharyngeal-cervical-brachial Guillain-Barre syndrome"Adv Clin Neurosci. 10. 173-186 (2000)
• [文献書誌] Odaka M: "Bickerstaff's brainstem encephalitis : diagnostic criteria and immunopathogenesis"Adv Clin Neurosci. 10. 207-221 (2000)
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