Advances in the pathogenic mechanisms of anti-glutamic acid decarboxylase antibody-associated neuroimmune diseases
10.3760/cma.j.cn113694-20250314-00134
- VernacularTitle:抗谷氨酸脱羧酶抗体相关神经免疫疾病的致病机制研究进展
- Author:
Lin BAI
1
;
Yang YU
;
Hongzhi GUAN
Author Information
1. 中国医学科学院北京协和医院神经科，北京 100730
- Publication Type:Journal Article
- Keywords:
Glutamate decarboxylase;
Neuroimmune disorders;
Antigen-specific T cells;
Cellular immunity
- From:
Chinese Journal of Neurology
2025;58(11):1221-1228
- CountryChina
- Language:Chinese
-
Abstract:
The pathogenic mechanisms underlying neuroimmune disorders associated with anti-glutamic acid decarboxylase (GAD) antibodies remain incompletely elucidated. This article systematically reviews the immunopathological mechanisms of this disease. In humoral immunity, anti-GAD antibodies target intracellular antigens and induce neuronal dysfunction, yet the mechanisms of antibody penetration across cell membranes remain undefined, and validated animal models confirming their pathogenicity are lacking. In cellular immunity, histopathological studies demonstrate T-lymphocyte infiltration in the central nervous system (CNS) of patients, while GAD antigen-specific T cells have been detected in peripheral blood and cerebrospinal fluid. However, the antigen specificity of CNS-infiltrating T cells and their potential association with GAD reactivity remain unclarified. Additionally, the CNS migration routes, functional phenotypes of these T cells, and their synergistic interplay with humoral immune responses require further investigation. Future research should focus on: (1) resolving the transmembrane mechanisms of anti-GAD antibodies; (2) defining the CNS trafficking pathways and functional roles of GAD antigen-specific T cells; (3) establishing reliable animal models to recapitulate disease-specific immune cascades. Elucidating these mechanisms will advance the development of precise diagnostic and therapeutic strategies.
