The clinical significance of S100B, APP, and CHI3L1 in autoimmune GFAP astrocytopathy

Background Autoimmune glial fibrillary acidic protein astrocytopathy (A-GFAP-A) is a recently defined immune-mediated disorder of the central nervous system (CNS). At present, diagnosis relies primarily on the detection of GFAP-IgG in cerebrospinal fluid (CSF); however, the limited specificity of this biomarker restricts its clinical utility. This study aimed to investigate the expression profiles and clinical relevance of additional protein biomarkers in A-GFAP-A. Methods A total of 19 patients with A-GFAP-A, 28 patients with neuromyelitis optica spectrum disorder (NMOSD), 12 patients with non-inflammatory neurological diseases (NINDC), and 12 healthy controls (HC) were enrolled. Serum and CSF levels of S100 calcium-binding protein B (S100B), amyloid precursor protein (APP), and chitinase-3-like protein 1 (CHI3L1) were quantitatively measured using enzyme-linked immunosorbent assay (ELISA). Disease severity was assessed using the Expanded Disability Status Scale (EDSS). Correlations between biomarker levels and clinical parameters were analyzed to evaluate their diagnostic and pathophysiological significance. Results Serum S100B levels were significantly higher in the A-GFAP-A group than in the NMOSD group ( p < 0.01), whereas CSF S100B levels were lower than those in NMOSD but remained higher than in the NINDC group ( p < 0.05). Serum APP concentrations were markedly elevated in A-GFAP-A compared with both NMOSD and HC ( p < 0.05 and p < 0.001, respectively). CSF APP levels did not differ significantly between A-GFAP-A and NMOSD but were significantly higher than in NINDC ( p < 0.001). CSF CHI3L1 was specifically and significantly increased in A-GFAP-A ( p < 0.01) and differed markedly from NINDC ( p < 0.01). Correlation analysis revealed a significant positive correlation between serum S100B and EDSS score (r = 0.642, p = 0.013). GFAP-IgG titers were strongly correlated with both serum and CSF APP levels (serum: r = −0.676, p = 0.008; CSF: r = 0.826, p = 0.001). Conclusion Serum S100B and APP, as well as CSF APP and CHI3L1, show potential as auxiliary diagnostic biomarkers for A-GFAP-A. These biomarkers may contribute to differential diagnosis and provide insights into disease mechanisms, thereby supporting more precise clinical management.