Related Experiment Video
Updated: Oct 16, 2026
Experimental Approaches for Biochemical Analysis of Glial Fibrillary Acidic Protein and Its Disease-associated Variants
Published on: November 28, 2025
Treatment-refractory autoimmune glial fibrillary acidic protein astrocytopathy: Clinical features, predictive models,
Shifeng Zhang1, Huilu Li2, Haiyan Yao3
1Department of Geriatrics, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510630, China; Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Key Clinical Specialty (Clinical Medicine Research Institute), The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Background And Objectives:
A subset of glial fibrillary acidic protein astrocytopathy experiences treatment-refractory disease course, yet the clinical and immunological features defining this subgroup remain incompletely characterized.
Methods:
Patients were classified as treatment-refractory (n = 23) or treatment-responsive (n = 30). Clinical, imaging, and outcomes were compared. For subgroup analyses, refractory patients were divided into three groups: no immunoadsorption/plasma exchange (IA/PE) (n = 9), IA/PE monotherapy (n = 4), and IA/PE plus rituximab (n = 10), with functional outcomes compared across groups. Immunoglobulin G (IgG) from refractory patients was applied to a passive transfer mouse model, and single-cell RNA sequencing was performed to explore underlying pathogenic mechanisms.
Results:
The treatment-refractory group had higher proportion of the meningoencephalomyelitis phenotype (82.6% vs. 53.3%, P = 0.026) and more frequent disturbances of consciousness (65.2% vs. 30.0%, P = 0.011), paraplegia (78.3% vs. 33.3%, P = 0.001), and peripheral nervous system involvement (89.5% vs. 22.2%, P < 0.001). Refractory patients had elevated cerebrospinal fluid glial fibrillary acidic protein and neurofilament light chain levels. Refractory patients more frequently exhibited spinal cord lesions involving three or more segments (65.2% vs. 21.4%, P = 0.002). Disability at last follow-up was greater in the refractory group (median modified Rankin Scale score 3 vs. 1, P < 0.0001). Firth penalized regression model identified peripheral nervous system involvement as the independent predictor of treatment refractoriness (odds ratio = 10.74, P = 0.006). Among refractory patients, the IA/PE-plus-rituximab group had significantly lower long-term mRS scores than the no-IA/PE group (adjusted P = 0.031). GFAPA-IgG from refractory patients induced CD45+ cell infiltration in mouse brain. Single cell analysis demonstrated activation of complement and inflammatory pathways, with astrocytes adopting a pro inflammatory state.
Conclusion:
Treatment refractory disease is marked by severe central and peripheral nervous system injury. Convergent clinical and experimental evidence provides a rationale for B cell targeted therapies.
