ギラン・バレー症候群の発症機序の解明

2001 Fiscal Year Annual Research Report

• Project/Area Number: 10557063
• Research Institution: Dokkyo University School of Medicine
• Principal Investigator: 結城 伸泰 獨協医科大学, 医学部, 助教授 (60285913)
• Keywords: ギラン・バレー症候群 / 分子相同性 / Campylobacter jejuni / IgG抗GM1抗体 / 動物モデル

Research Abstract

研究成果:
(1)ウサギ13羽にウシ脳ガングリオシド、Freund完全アジュバントを3週に1回感作を繰り返した。IgM抗GM1抗体産生が誘導されたばかりでなく、IgGヘクラススイッチした。初回感作後5-11週で全例に運動麻痺が生じた。末梢神経に軸索型ギラン・バレー症候群と同様の病理組織学的所見が得られた。これに対して、アジュバント対照群10羽では24週まで1羽も発症しなかった。ウサギ末梢神経よりガングリオシドを抽出し、薄層クロマトグラム-ブロッティングと質量分析を組み合わせて、発症ウサギの血漿IgGが認識する分子がGM1であることを確認した。ウサギ11羽にGM1、Freund完全アジュバントを感作し、IgG抗GM1抗体産生が誘導され、9羽に運動麻痺が生じた。
軸索型ギラン・バレー症候群の動物モデルを樹立した。このモデルにおいては、免疫原としても標的抗原としてもGM1が重要な分子であることが明らかにされた。
(2)ウシ脳ガングリオシド、GM1をウサギに感作し、感作ガングリオシド至適量の検討、電気生理、免疫組織学的検討を行った。また、ガラクトセレブロシド感作による脱髄性ニューロパチーモデルと比較した。ガングリオシド投与量に依存して発症率が増加し、2.5mg感作群で全例が重度の麻痺を呈した。よって本モデルでは、ウシ脳ガングリオシド2.5mg感作が適切と考えられた。電気生理学的検討では、ガラクトセレブロシド感作群では急性期より脱髄所見を呈した。それに対し、軸索型ギラン・バレー症候群モデルでは、急性期は一部のF波消失を認めるのみで、複合筋活動電位振幅や伝導速度は異常なかった。免疫組織学的検討では、神経根、馬尾に限局して軸索にIgG沈着を認めた。したがって本モデルでは、血液神経関門が脆弱な神経根に限局して軸索障害が起こることが示唆された。

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 IgG 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] 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] Koga M: "Antibodies to GD3, GT3, and O-acetylated species in Guillain-Barre and Fisher's syndromes : Their association with cranial nerve dysfunction"J Neurol Sci. 164. 50-55 (1999)
• [Publications] Yuki N: "Autoantibodies to GM1b and GalNAc-GD1a : relationship to Campylobacter jejuni infection and acute motor axonal neuropathy in China"J Neurol Sci. 164. 134-138 (1999)
• [Publications] Odaka M: "Bilateral ballism in a patient with overlapping Fisher's and Guillain-Barre syndromes"J Neurol Neurosurg Psychiatry. 67. 206-208 (1999)
• [Publications] Odaka M: "Antibodies to GD1 α and GQ1β in Guillain-Barre syndrome and the related disorders"J Neurol Sci. 165. 126-132 (1999)
• [Publications] Yuki N: "Pathogenesis of Guillain-Barre and Miller Fisher syndromes subsequent to Campylobacter jejuni enteritis"Jpn J Infect Dis. 52. 99-105 (1999)
• [Publications] Mori M: "IgG anti-GQ1b positive acute ataxia without ophthalmoplegia"J Neurol Neurosurg Psychiatry. 67. 668-670 (1999)
• [Publications] Ohtsuka K: "Immunoadsorption therapy for Fisher syndrome associated with IgG anti-GQ1b antibody"Am J Ophthalmol. 125. 404-406 (1998)
• [Publications] Kitazawa K: "Guillain-Barre syndrome associated with IgG anti-GM1b antibody subsequent to Mycoplasma pneumoniae infection"J Neurol Sci. 156. 99-101 (1998)
• [Publications] Yuki N: "Guillain-Barre syndrome and Fisher's syndrome following Campylobacter jejuni infection"Ann NY Acad Sci. 845. 330-340 (1998)
• [Publications] Yuki N: "Postinfection sensory neuropathy associated with IgG anti-GD1b antibody"Ann Neurol. 43. 685-687 (1998)
• [Publications] Tagawa Y: "Ability to remove immunoglobulins and anti-ganglioside antibodies by plasma exchange double-filtration plasmapheresis and immunoadsorption"J Neurol Sci. 157. 90-95 (1998)
• [Publications] Odaka M: "N-glycolylneuraminic acid-containing GM1 is a new molecule for serum antibody in Guillain-Barre syndrome"Ann Neurol. 43. 829-834 (1998)
• [Publications] Yuki N: "Minimal number of plasma exchanges needed to reduce immunoglobulin in Guillain-Barre syndrome"Neurology. 51. 875-877 (1998)
• [Publications] Yuki N: "Fisher's syndrome and group A streptococcal infection"J Neurol Sci. 160. 64-66 (1998)
• [Publications] Kashihara K: "IgG anti-GT1a antibodies which do not cross react with GQ1b ganglioside in a pharyngeal-cervical-brachial variant of Guillain-Barre syndrome"J Neurol Neurosurg Psychiatry. 65. 799 (1998)
• [Publications] Yuki N: "Isolated internal ophthalmoplegia associated with immunoglobulin G anti-GQ1b antibody"Neurology. 51. 1515-1516 (1998)
• [Publications] Tagawa Y: "Antiganglioside antibodies in various episodes in a patient with recurrent Guillain-Barre syndrome"J Neurol Neurosurg Psychiatry. 65. 952 (1998)
• [Publications] Kuwabara S: "Two patterns of clinical recovery in Guillain-Barre syndrome with IgG anti-GM1 antibody"Neurology. 51. 1656-1660 (1998)
• [Publications] 結城伸泰: "新内科治療ガイド:治療戦略の立て方と病態に応じた治療の実際"文光堂. 4 (1999)
• [Publications] 結城伸泰: "新内科治療ガイド:治療戦略の立て方と病態に応じた治療の実際"文光堂. 3 (1999)
• [Publications] 結城伸泰: "免疫学からみた神経系と神経疾患"日本医学館. 5 (1999)
• [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)