eterogeneity and continuum of clinical features in autoimmune autonomic ganglionopathy

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09695
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kumamoto University
• Principal Investigator: Nakane Shunya 熊本大学, 医学部附属病院, 特任教授 (70398022)
• Co-Investigator(Kenkyū-buntansha): 樋口 理 独立行政法人国立病院機構長崎川棚医療センター(臨床研究部), その他の研究科, 研究員(移行) (50361720)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 自己免疫性自律神経節障害 / 抗自律神経節アセチルコリン受容体抗体

Outline of Final Research Achievements

The clinical associations of anglionic acetylcholine receptor (gAChR) have not yet been described fully. It is not known whether central nervous system (CNS) involvement and endocrine disorders are the extra-autonomic features of autoimmune autonomic ganglionopathy (AAG), or whether it is related to circulating anti-gAChR antibodies (Abs). We identified prospectively 179 Abs-positive AAG patients in Japan. Luciferase immunoprecipitation systems were conducted to detect anti-gAChR Abs. Patients with AAG demonstrated widespread autonomic dysfunction. In particular, orthostatic hypotension and lower gastrointestinal tract dysfunction were frequently observed. Seropositive AAG patients showed a range of clinical features including CNS involvement (33%), endocrine disorders (15%), other autoimmune disease (30%), and tumors (10%). And most showed marked improvement in the clinical status and the levels of anti-gAChR Abs with immunotherapies.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

自己免疫性自律神経節障害は自律神経系が免疫異常の標的となる比較的新しい疾患概念である．本症では抗自律神経節アセチルコリン受容体抗体は病原性自己抗体として病態の鍵となる役割を果たす．我々は2012年にこの自己抗体測定を本邦で初めて可能とし，日本における自己免疫性自律神経節障害症例の調査に努めてきた．本症は自律神経系外の症候（中枢神経系障害，感覚障害，内分泌障害）や併存症（膠原病など），小児症例が存在することが判ってきた．この「多様性」が本症の診断しにくさ，難治化につながっていることがわかった．また慢性疲労症候群など本症と類似の症候を呈する疾患群との異同の解明も今後の研究上の重要な課題である．