Patients with suspected benign tumors and glial fibrillary acidic protein autoantibody: an analysis of five cases.

Aim: To investigate the clinical features of five glial fibrillary acidic protein (GFAP) antibody positive patients with suspected benign tumors and explore its underlying pathogenesis. Materials and methods: Overall, 1018 serum and cerebrospinal fluid (CSF) samples were tested by indirect immunofluorescence assay and data from five patients with suspected tumors and positive for GFAP autoantibody in the CSF were analyzed retrospectively. Results: The positive rate of GFAP antibody in the serum and CSF was 3.93% by indirect immunofluorescence assay. Tumors were diagnosed before or after neurologic onset in 5 of 40 patients (12.5%) and no deterioration of the tumors was found during the long-term follow-up. Of the five patients, one patient suffered a thyroid nodule, one patient had a small nodule in the left lung, two patients suffered meningiomas, and one patient had a suspicious eosinophilic granuloma. Conclusion: GFAP autoimmunity may be a paraneoplastic immune response with a low frequency of tumor in Chinese patients with GFAP astrocytopathy.

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.

Autoimmune inflammatory meningoencephalitis in a patient negative for glial fibrillary acidic protein-specific immunoglobulin G.

BACKGROUND: In this study, we describe clinical findings in a patient with autoimmune inflammatory meningoencephalitis who was negative for antibodies against glial fibrillary acidic protein (GFAP-IgG). METHODS: Serum and cerebral spinal fluid (CSF) samples were collected from the patient as part of a study of 520 patients with neurological syndromes. Antibodies against GFAP and other proteins associated with neurological disorders were measured by rat brain- and cell-based indirect immunofluorescence assays. RESULTS: A 42-year-old female was diagnosed with autoimmune inflammatory meningoencephalitis. She experienced a subacute and relapsing course with decreased vision, fever, headache, ataxia, hemiplegia, and disturbance of consciousness. Brain magnetic resonance imaging showed extensive lesions in the white matter along the ventricle, brainstem, right internal capsule, and meninges. The patient responded well to steroid treatment. Examination of CSF revealed a normal white blood cell count and protein level. Serum and CSF were negative for GFAP-specific antibodies and all other autoantibodies tested. Immunohistochemical staining of a brain biopsy collected during relapse revealed chronic inflammation and severe edema. Extensive and strong staining of CD163+ macrophages were evident throughout the lesions; however, CD3+ cells were rare and CD138+ and CD20+ cells were absent. CONCLUSION: We describe a case of subacute corticosteroid-responsive nonvasculitic autoimmune inflammatory meningoencephalitis in the absence of GFAP-IgG. The pathological features were distinct from those of patients with GFAP-IgG-positive meningoencephalitis, suggesting that nonvasculitic autoimmune inflammatory meningoencephalitis is a heterogeneous neurological syndrome.

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.

Glutamic Acid Decarboxylase Antibody in a Patient with Myelitis: A Retrospective Study.

OBJECTIVE: The aim of this study was to evaluate the positive rate of serum glutamic acid decarboxylase (GAD) autoantibody in patients with myelitis and to describe the clinical findings in patients with positive GAD antibody. METHODS: Serum samples were collected from 390 patients with myelitis, including 210 patients positive for aquaporin 4 (AQP4) antibody and 180 patients negative for AQP4. GAD65 antibody was measured by an indirect immunofluorescence assay. RESULTS: Only 1 serum and cerebral spinal fluid sample from 390 patients (0.26%) was positive for anti-GAD antibodies. The patient was a female with relapsing myelitis and a thymic mass. Thymic resection was undertaken, and pathological examination revealed a benign thymic cyst. Extensive infiltration of lymphocytes positive for CD3, CD4, CD8 and CD20 was found. Immunohistochemistry showed positive expression of GAD65 in the cyst. CONCLUSIONS: Although serum GAD65 antibodies were present in a patient, it is not recommended to routinely screen for GAD65 antibodies in patients with myelitis because of their rare occurrence. However, screening for GAD65 antibodies should be considered in patients who have been diagnosed with cancer or a thymic abnormality.

Overlapping Autoimmune Syndromes in Patients With Glial Fibrillary Acidic Protein Antibodies.

BACKGROUND: Glial fibrillary acidic protein (GFAP) astrocytopathy, an autoimmune central nervous system disorder with a specific GFAP-IgG, often coexists with other antibodies. OBJECTIVE: The aim of this article was to study overlapping syndromes in autoimmune GFAP astrocytopathy. METHODS: Antibody was detected by indirect immunofluorescence assay. Patient data were analyzed retrospectively. RESULTS: Thirty patients with positive GFAP-IgG were included, of whom 10 were defined as overlapping syndrome. Four patients with positive aquaporin-4 (AQP4)-IgG, two with N-methyl-d-aspartate receptor-IgG, three with unknown neuronal antibodies, and one with double AQP4 and myelin oligodendrocyte glycoprotein-IgG were identified. GFAP-IgG and other specific antibodies occurred simultaneously at the initial attack in eight patients. The main symptoms included fever, headache, ataxia, psychosis, hypersomnia, dyskinesia, dementia, seizure, myelitis, and optical symptoms. Brain magnetic resonance imaging in four patients revealed characteristic radial enhancing patterns in the white matter. Cortical abnormalities were found in four patients. Other brain abnormalities occurred in the hypothalamus, midbrain, pons, medulla, cerebellum, and meninges. Six patients exhibited lesions in the spinal cord. In a subgroup study, patients with overlapping syndrome were younger at onset than those with non-overlapping syndrome. CONCLUSION: Overlapping antibodies are common in GFAP astrocytopathy.