Glycolipids shielding target gangliosides: determinants of pathogenesis and clinical presentation of Guillain-Barre syndrome

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07437
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Yamaguchi University
• Principal Investigator: KOGA Michiaki 山口大学, 大学院医学系研究科, 准教授 (60383014)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ギラン・バレー症候群 / ガングリオシド / 自己抗体

Outline of Final Research Achievements

Several gangliosides have been identified as target epitopes of autoantibodies in Guillain-Barre syndrome, and anti-ganglioside antibodies (Abs) are considered to be involved in its pathogenesis. However, clinical pictures of patients with same anti-ganglioside Ab pattern considerably varies from case to case, and the mechanism by which the same Abs can produce a variety of clinical manifestations has not been clarified. In this study, the hypothesis that shielding of the target gangliosides by other glycolipids that adjacently expressed is the cause of the diverse clinical features was examined, focusing on the association between anti-GT1a Abs and bulbar palsy. The results failed to prove the hypothesis, but identified several glycolipid candidates that forms a complex with GT1a to create a new target for bulbar palsy. The viewpoint that multiple antigens create novel target epitopes by forming complex would be important for clarifying the pathogenesis of Ab-mediated diseases.

Free Research Field

脳神経内科（神経免疫学、末梢神経学）

Academic Significance and Societal Importance of the Research Achievements

自己抗体介在性の難病は数多くあるが、自己抗体がどのような機序で臓器障害をきたすか十分に明らかにされていないことが多い。そのような現状は、標的抗原候補を一つずつ解析していることに起因しており、今回の検討で明らかとなったように複数の抗原が複合体を形成することで標的抗原を作り出しているという観点が病態解明の鍵となることが本研究により示唆された。