抗ガングリオシド抗体産生機構の解明

• Project/Area Number: 18390263
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Dokkyo Medical University
• Principal Investigator: 結城 伸泰 獨協医大, 医学部, 助教授 (60285913)
• Co-Investigator(Kenkyū-buntansha): 松本 幸恵 獨協医科大学, 医学部, 助手
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥15,940,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥1,440,000); Fiscal Year 2007: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2006: ¥9,700,000 (Direct Cost: ¥9,700,000)
• Keywords: Campylobacter jejuni / リポオリゴ糖 / ガングリオシド / 自己抗体

Research Abstract

(1)Campylobacter jejuniリポオリゴ糖(LOS)とガングリオシドによるBAFF分子誘導の結果
GM1およびGD1a様糖鎖を有するC.jejuni LOSや菌体を感作したGalNAcT^<-/->マウスの脾臓からMac-1陽性細胞を単離し、BAFF mRNA量をリアルタイムRT-PCRで、BAFFタンパク/脾臓をウエスタンブロットで調べた。ガングリオシド、LOS、菌体を感作したマウスでは、未感作マウスの3、5、7倍量のBAFF mRNAが、また、7、19、52倍量のBAFFタンパクが発現していた。血清中のBAFFレベルは、C.jejuni菌体を感作したマウスで顕著に上がっていた。一方、B細胞上のBAFF-Rの発現はいずれの感作でも未感作時に比べてほとんど変化していないのに対し、TACIの発現はC.jejuni LOSや菌体を感作したマウスでは上がっていた。これらの結果から、C.jejuni LOSや菌体はガングリオシドに比べ、Mac-1陽性細胞におけるBAFFの発現やB細胞上のTACIをより強く誘導することがわかった。
(2)「BAFF存在下では自己ガングリオシドに反応して抗体が産生されるか?」に関する中間報告
抗ガングリオシド抗体誘導におけるBAFFの重要性を実証するため、リコンビナントBAFF投与下での感作実験を計画した。その予備実験として、リコンビナントBAFFを投与し血中濃度をモニターしたが、BAFFの効果を期待できる濃度を維持することが困難であることが判明した。
そこで、Garvan Institute of Medical ResearchのMacKay博士からBAFFトランスジェニックマウスの供与を受け、繁殖中である。
(3)GM1糖鎖を認識する免疫グロブリン遺伝子の単離に関する中間報告
ハイブリドーマGB2(抗GM1抗体)の免疫グロブリン重鎖、軽鎖遺伝子を単離した。

Research Products

• [Journal Article] Recognition characteristics of monoclonal antibodies that are cross-reactive with gangliosides and lipo-oligosaccharide from Campylobacter jejni strains associated with Guillain-Barre and Fisber syndromes. (2007)
  • Author(s): Houliston RS
  • Journal Title: Biochemistry 46 Pages: 36-44
• [Journal Article] Leukocyte and complement activation by GM1-specific antibodies is associated with acute motor axonal neuropathy in rabbits. (2007)
  • Author(s): Van Sorge NM
  • Journal Title: J Neuroimmunol 182 Pages: 116-123
• [Journal Article] Ganglioside-specific IgG and IgA recruit leukocyte effector functions in Guillain-Barre syndrome. (2007)
  • Author(s): Van Sorge NM
  • Journal Title: J Neuroimmunol 182 Pages: 177-184
• [Journal Article] Treatment of Miller Fisher syndrome and other related disorders. Treatment for Fisher syndrome, Bickerstaffs brainstem encephalitis and related disorders. (2007)
  • Author(s): Overell J
  • Journal Title: Cochrane Database Syst Rev 1(CD004761)
• [Journal Article] Comprehensive analysis of bacterial risk factors for the development of Guillain-Barre syndrome after Campylobacter jejuni enteritis. (2006)
  • Author(s): Koga M
  • Journal Title: J Infect Dis 193 Pages: 547-555
• [Journal Article] Rhinolalia after diarrhea : a sole motor symptom occurring in post-infectiousneuropathy associated with anti-ganglioside antibodies. (2006)
  • Author(s): Kamitani T
  • Journal Title: Eur J Newrol 13 Pages: 203-204
• [Journal Article] Isolated abducens nerve palsy as a regional variant of Guillain-Barre syndrome. (2006)
  • Author(s): Tatsumoto M
  • Journal Title: J Newrol Sci 243 Pages: 35-38
• [Journal Article] Electrophysiological subtypes and prognosis of childhood Guillain-Barre syndrom in Japan. (2006)
  • Author(s): Nagasawa K
  • Journal Title: Muscle Nerve 33 Pages: 766-770
• [Journal Article] Identification of a sialate O-acetyltransferase from Campylobacter jejuni : demonstration of direct transfer to the C-9 position of terminal α-2,8-linked sialic acid. (2006)
  • Author(s): Houliston RS
  • Journal Title: J Biol Chem 281 Pages: 11480-11486
• [Journal Article] Severe cranial nerve involvement in a patient with monoclonal anti-MAG/SGPG IgM antibody and localized hard palate amyloidosis. (2006)
  • Author(s): Yoshida T
  • Journal Title: J Neurol Sci 244 Pages: 167-171
• [Journal Article] Campylobacter coli enteritis and Guillain-Barre syndrome : no evidence of molecular mimicry and serological relationship. (2006)
  • Author(s): Funakoshi K
  • Journal Title: J Neurol Sci 246 Pages: 163-168
• [Journal Article] Spectrum of neurological diseases associated with antibodies to minor gangliosides GM1b and GalNAc-GD1a. (2006)
  • Author(s): Tatsumoto M
  • Journal Title: J Neuroimmunol 177 Pages: 201-208
• [Journal Article] Ganglioside mimicry as a cause of Guillain-Barre syndrome. (2006)
  • Author(s): Komagamine T
  • Journal Title: CNS ＆ Neurological Disorders- Drug Targets 5 Pages: 391-400
• [Journal Article] Rituximab therapy in chronic inflammatory demyelinating polyradiculoneuropathy with anti-SGPG IgM antibody. (2006)
  • Author(s): Gono T
  • Journal Title: J Clin Neurosci 13 Pages: 683-687
• [Journal Article] Bacterial infections in Guillain-Barre and Fisher syndromes. (2006)
  • Author(s): Yuki N
  • Journal Title: Curr Opin Newrol 19 Pages: 451-457
• [Journal Article] Relationship of bacterial strains to clinical syndromes of Campylobacter-associated neuropathies. (2006)
  • Author(s): Kimoto K
  • Journal Title: Neurology 67 Pages: 1837-1843
• [Journal Article] High affinity of anti-GM1 antibodies associated with disease onset in experimental neuropathy. (2006)
  • Author(s): Comin R
  • Journal Title: J Neurosci Res 84 Pages: 1085-1090