Astrocytic damage in glial fibrillary acidic protein astrocytopathy during initial attack.

OBJECTIVE: Determination of glial fibrillary acidic protein (GFAP), aquaporin 4 (AQP4), and myelin oligodendrocyte glycoprotein (MOG) levels in cerebrospinal fluid (CSF), and astrocytic damage analysis in patients with GFAP astrocytopathy (GFAP-A) and other conditions. METHODS: GFAP, AQP4, and MOG levels in CSF were detected via enzyme-linked immunosorbent assays. Anti-GFAP, anti-AQP4, and anti-MOG IgGs were detected via indirect immunofluorescence assays. RESULTS: In 32 GFAP-Astrocytopathy patients, CSF GFAP was significantly higher during acute exacerbation than it was in patients with MOG encephalomyelitis, multiple sclerosis, autoimmune encephalitis, and an "other inflammatory neurological disorders" group (all p < 0.0001). CSF GFAP levels were slightly higher in the GFAP-A group than in an anti-AQP4 IgG-positive neuromyelitis optica spectrum disorder group (p = 0.012). There were no significant differences between the CSF MOG and AQP4 levels in the GFAP-A group and those of other groups. CSF GFAP levels were significantly reduced after steroid treatment (p = 0.011). CSF GFAP levels differed significantly in GFAP-Astrocytopathy patients with and without encephalitis (p = 0.016). In GFAP-Astrocytopathy patients, CSF GFAP was correlated with Expanded Disability Status Scale (EDSS) score during attack (r = 0.545, p = 0.001). In follow-up examinations however, in GFAP-Astrocytopathy patients CSF GFAP level was not correlated with EDSS score 6 months later. CONCLUSIONS: CSF GFAP level and pathological examination of GFAP-Astrocytopathy patients revealed astrocyte damage. CSF GFAP level was associated with steroid treatment at the acute stage, therefore CSF GFAP may be a sensitive biomarker with respect to the effects of therapy during the acute stage.

Screening for autoantibodies in inflammatory neurological syndrome using fluorescence pattern in a tissue-based assay: Cerebrospinal fluid findings from 793 patients.

BACKGROUND: To evaluate indirect immunofluorescence patterns of auto-antibodies and the targeting antigens to Immunoglobulin Gs (IgGs) in the cerebrospinal fluid (CSF) by a tissue-based assay(TBA). METHODS: CSF samples were collected from 793 patients. Auto-antibody levels were measured via an immunofluorescence assay. RESULTS: 110 (13.9%) CSF samples with a specific response were confirmed. Of these, 37 showed a neuronal pattern, 57 an astrocyte pattern, 7 a neuronal and astrocyte pattern, and 9 samples showed an oligodendrocyte pattern. In the neuronal antibody group, 16 patients had NMDAR-IgGs, 3 had LGi1-IgGs, 2 had AMPA2-IgGs, 2 had GAD65-IgGs, 1 patient had GABA-IgGs, and 1 patient had overlapping NMDAR-IgGs and AQP4-IgGs. Of the unidentified neuronal antibodies, two were cellular surface antibodies, three were cellular surface and cytoplasm antibodies, three were cytoplasm antibodies, and four were nuclear and cytoplasm antibodies. Among the 57 patients with the astrocyte pattern, 28 patients were positive for AQP4-IgGs, 21 were positive for GFAP-IgGs, 5 patients had overlapping AQP4 and GFAP-IgGs, and 3 patients had an unidentified antigen. Seven patients showed neuronal and astrocyte patterns simultaneously; four of them had unknown neuronal antibodies. In the patients with an oligodendrocyte pattern, one was positive for MOG-IgGs and four for MBP-IgGs. CONCLUSIONS: The TBA is helpful for diagnosing autoimmune neurological syndrome, especially in patients with unknown antibodies and antigens. Presence of unidentified antibodies against neuronal or glial cells could be an interesting finding, but should be investigated in future studies which incorporate parallel serum samples at an appropriate IgG dilution.