Glial Fibrillary Acidic Protein Autoantibody Research Articles

Magnetic Resonance Imaging Characteristics of Autoimmune Glial Fibrillary Acidic Protein (GFAP) Astrocytopathy: A Pediatric Series in Southwest China.

To investigate and summarize the magnetic resonance imaging (MRI) manifestations of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy in children. We retrospectively analyzed data from 17 pediatric patients with autoimmune GFAP astrocytopathy confirmed by the detection of GFAP autoantibodies in cerebrospinal fluid in our single-center. Furthermore, we reviewed current literature and summarized previous findings on the MRI characteristics of this disease in children. In these 17 patients, the clinical manifestations and results of CSF analysis were suggestive of autoimmune disorder, with a good improvement. The lesions on MRI were most commonly located in the bilateral basal ganglia (70.6%), thalamus (64.7%), cerebral white matter (29.4%). 93.3% of the cerebral lesions were relatively scattered and small, 80% of the spinal lesions presented as longitudinally extensive ones. Both periventricular radial linear (PVRL) (53.8%) and punctate or linear enhancement in basal ganglia and thalamus (53.8%) were commonly observed, followed by the leptomeningeal enhancement (46.2% in the brain and 62.5% in the spinal cord). We then included 55 pediatric patients with MRI data from current literature in our analysis (n = 72, 44 males). Our results revealed similar MRI findings but the enhancement pattern between our series and previously published cases, that is, leptomeningeal enhancement in the brain 46.2% vs 31.4%, in spinal cord 62.5% vs 18.4%, and PVRL enhancement 53.8% vs 11.2%. There were no detailed reports on punctate or linear enhancement. The MRI characteristics of autoimmune GFAP astrocytopathy in children could be suggestive. Scattered and small lesions (especially punctate or linear) in the bilateral thalamus, basal ganglia, and white matter, as well as longitudinally extensive spinal cord lesions (if present), with punctate, PVRL and leptomeningeal enhancement might be a distinct indication for the early diagnosis of this disorder.

Plasma autoantibodies to glial fibrillary acidic protein (GFAP) react with brain areas according to Braak staging of Parkinson’s disease

Idiopathic Parkinson’s disease (PD) is characterized by a progredient degeneration of the brain, starting at deep subcortical areas such as the dorsal motor nucleus of the glossopharyngeal and vagal nerves (DM) (stage 1), followed by the coeruleus–subcoeruleus complex; (stage 2), the substantia nigra (SN) (stage 3), the anteromedial temporal mesocortex (MC) (stage 4), high-order sensory association areas and prefrontal fields (HC) (stage 5) and finally first-order sensory association areas, premotor areas, as well as primary sensory and motor field (FC) (stage 6). Autoimmunity might play a role in PD pathogenesis. Here we analyzed whether anti-brain autoantibodies differentially recognize different human brain areas and identified autoantigens that correlate with the above-described dissemination of PD pathology in the brain. Brain tissue was obtained from deceased individuals with no history of neurological or psychiatric disease and no neuropathological abnormalities. Tissue homogenates from different brain regions (DM, SN, MC, HC, FC) were subjected to SDS-PAGE and Western blot. Blots were incubated with plasma samples from 30 PD patients and 30 control subjects and stained with anti-IgG antibodies to detect anti-brain autoantibodies. Signals were quantified. Prominent autoantigens were identified by 2D-gel-coupled mass spectrometry sequencing. Anti-brain autoantibodies are frequent and occur both in healthy controls and individuals with PD. Glial fibrillary acidic protein (GFAP) was identified as a prominent autoantigen recognized in all plasma samples. GFAP immunoreactivity was highest in DM areas and lowest in FC areas with no significant differences in anti-GFAP autoantibody titers between healthy controls and individuals with PD. The anti-GFAP autoimmunoreactivity of different brain areas correlates with the dissemination of histopathological neurodegeneration in PD. We hypothesize that GFAP autoantibodies are physiological but might be involved as a cofactor in PD pathogenesis secondary to a leakage of the blood–brain barrier.

Evaluation of cell-based and tissue-based immunofluorescent assays for detection of glial fibrillary acidic protein autoantibodies in the cerebrospinal fluid of dogs with meningoencephalitis of unknown origin and other central nervous system disorders.

To evaluate whether cell-based and tissue-based immunofluorescent assays (IFAs) run in parallel could be used to detect glial fibrillary acidic protein (GFAP) autoantibodies in the CSF of dogs with meningoencephalitis of unknown origin (MUO) and other CNS disorders. 15 CSF samples obtained from dogs with presumed MUO (n = 5), CNS disease other than MUO (5), and idiopathic epilepsy (5). All CSF samples underwent parallel analysis with a cell-based IFA that targeted the α isoform of human GFAP and a tissue-based IFA that involved mouse brain cryosections. Descriptive data were generated. Only 1 CSF sample yielded mildly positive results on the cell-based IFA; that sample was from 1 of the dogs with presumed MUO. The remaining 14 CSF samples tested negative on the cell-based IFA. All 15 CSF samples yielded negative results on the tissue-based IFA. Results suggested that concurrent use of a cell-based IFA designed to target the human GFAP-α isoform and a tissue-based IFA that involved mouse tissue cryosections was inadequate for detection of GFAP autoantibodies in canine CSF samples. Given that GFAP autoantibodies were likely present in the CSF samples analyzed, these findings suggested that epitopes differ substantially between canine and human GFAP and that canine GFAP autoantibody does not bind to mouse GFAP. Without a positive control, absence of GFAP autoantibody in this cohort cannot be ruled out. Further research is necessary to develop a noninvasive and sensitive method for diagnosis of MUO in dogs.

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.

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy: A Review of the Literature.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is an autoimmune disease of the nervous system first defined in 2016. GFAP autoantibody, especially IgG that binds to GFAPα, has been reported in the cerebrospinal fluid (CSF) and serum of patients with GFAP astrocytopathy. The positive predictive value of GFAP antibody in the CSF is higher than in the serum. Tissue-based assay (TBA) and cell-based assay (CBA) are both recommended methods for the detection of GFAP antibody. GFAP astrocytopathy is accompanied by neoplasms, but the relationship between virus infection and GFAP astrocytopathy is unclear. GFAP antibody itself does not induce pathological changes; it is only a biomarker for the process of immune inflammation. The pathology of GFAP astrocytopathy in humans is heterogeneous. GFAP astrocytopathy is commonly diagnosed in individuals over 40 years old and most patients have an acute or subacute onset. Clinical manifestations include fever, headache, encephalopathy, involuntary movement, myelitis, and abnormal vision. Lesions involve the subcortical white matter, basal ganglia, hypothalamus, brainstem, cerebellum, and spinal cord. The characteristic MRI feature is brain linear perivascular radial gadolinium enhancement in the white matter perpendicular to the ventricle. Currently, there are no uniform diagnostic criteria or consensus for GFAP astrocytopathy and coexisting neural autoantibodies detected in the same patient make the diagnosis difficult. A standard treatment regimen is yet to be developed. Most GFAP astrocytopathy patients respond well to steroid therapy although some patients are prone to relapse or even die.

Increased Levels of Circulating Glial Fibrillary Acidic Protein and Collapsin Response Mediator Protein-2 Autoantibodies in the Acute Stage of Spinal Cord Injury Predict the Subsequent Development of Neuropathic Pain.

Neuropathic pain develops in 40-70% of spinal cord injury (SCI) patients and markedly compromises quality of life. We examined plasma from SCI patients for autoantibodies to glial fibrillary acidic protein (GFAP) and collapsin response mediator protein-2 (CRMP2) and evaluated their relationship to the development of neuropathic pain. In study 1, plasma samples and clinical data from 80 chronic SCI patients (1-41 years post-SCI) were collected and screened for GFAP autoantibodies (GFAPab). Results from study 1 indicated that GFAPab were present in 34 of 80 (42.5%) patients, but circulating levels did not correlate with the occurrence of neuropathic pain. In study 2, longitudinal plasma samples and clinical data were collected from 38 acute SCI patients. The level of GFAPab measured at 16 ± 7 days post-SCI was found to be significantly higher in patients that subsequently developed neuropathic pain (within 6 months post-SCI) than patients who did not (T = 219; p = 0.02). In study 3, we identified CRMP2 as an autoantibody target (CRMP2ab) in 23% of acute SCI patients. The presence of GFAPab and/or CRMP2ab increased the odds of subsequently developing neuropathic pain within 6 months of injury by 9.5 times (p = 0.006). Our results suggest that if a causal link can be established between these autoantibodies and the development of neuropathic pain, strategies aimed at reducing the circulating levels of these autoantibodies may have therapeutic value.

Glial fibrillary acidic protein (GFAP) is a novel biomarker for the prediction of autoimmune diabetes.

Glial fibrillary acidic protein (GFAP) is expressed in peri-islet Schwann cells, as well as in glia cells, and has been reported to be an autoantigen candidate for type 1 diabetes mellitus (T1DM). We confirmed that the production of the autoantibodies GFAP and glutamic acid decarboxylase 65 (GAD65) was increased and inversely correlated with the concentration of secreted C peptide in female nonobese diabetic mice (T1DM model). Importantly, the development of T1DM in female nonobese diabetic mice at 30 wk of age was predicted by the positive GFAP autoantibody titer at 17 wk. The production of GFAP and GAD65 autoantibodies was also increased in KK-Ay mice [type 2 diabetes mellitus (T2DM) model]. In patients with diabetes mellitus, GFAP autoantibody levels were increased in patients with either T1DM or T2DM, and were significantly associated with GAD65 autoantibodies but not zinc transporter 8 autoantibodies. Furthermore, we identified a B-cell epitope of GFAP corresponding to the GFAP autoantibody in both mice and patients with diabetes. Thus, these results indicate that autoantibodies against GFAP could serve as a predictive marker for the development of overt autoimmune diabetes.-Pang, Z., Kushiyama, A., Sun, J., Kikuchi, T., Yamazaki, H., Iwamoto, Y., Koriyama, H., Yoshida, S., Shimamura, M., Higuchi, M., Kawano, T., Takami, Y., Rakugi, H., Morishita, R., Nakagumi, H. Glial fibrillary acidic protein (GFAP) is a novel biomarker for the prediction of autoimmune diabetes.

GFAP Antibody Detection Using Interdigital Coplanar Waveguide Immunosensor

Glioma is the most common primary brain tumor with its early detection remaining a challenge. Autoantibodies against glial fibrillary acidic protein (GFAP) have shown the highest differential expression compared with the other glioma expressed autoantibodies. In this paper, an immunosensor to detect GFAP antibody levels is developed using an interdigital coplanar waveguide (ID-CPW). The ID-CPW is fabricated on an SiO2/Si substrate with the CPW and inter-digital electrode conducting layers made using Cr/Au. The sensor is functionalized, and protein extracted from astrocytes is immobilized on the surface. Sensitivity and dynamic range are ascertained using varying the concentrations of a commercial, polyclonal antibody to GFAP. The electrical detection of antigen-antibody binding is performed in both dry and wet environments across the 1–25-GHz range. Our results show that the proposed sensor can detect antibodies to GFAP to a minimum concentration of 2.9 pg/ml with a turnaround time in less than 3 h. Our electrical measurements indicate an improved sensitivity compared with the state-of-the-art optical detection methods. The immunosensor, developed to detect antibody against GFAP, is the first to show the applicability in the detection of glioma using the GFAP autoantibodies.

Serum GFAP autoantibody as an ELISA-detectable glioma marker

Glioma is the most common primary brain tumor, yet the high cost of diagnostic imaging has made early detection of asymptomatic glioma a formidable challenge. Thus, the development of a convenient, sensitive, and cost-effective diagnostic strategy, such as enzyme-linked immunosorbent assay (ELISA) based on glioma-specific and World Health Organization (WHO) grade-specific autoantibody serum markers, is necessary. To this end, a comparative proteomic analysis based on two-dimensional western blotting was carried out with the sera of glioma patients and normal controls. Of the 11 novel glioma-expressed autoantibodies, the autoantibody against glial fibrillary acidic protein (GFAP) showed the highest differential expression. To investigate the potential clinical utility of the GFAP autoantibody as an early diagnostic marker for glioma, an ELISA-based assay was developed and validated with sera from glioma patients with WHO grades II (n = 19), III (n = 17), and IV (n = 24). The GFAP autoantibody level directly correlated with WHO grade and tumor volume. Sera from patients of non-glioma brain tumors, as well as non-brain tumors, showed much lower levels of GFAP autoantibody than those of the glioma patients, indicating that elevated GFAP autoantibody is specific to glioma patients. Analysis of the receiver operating characteristics curve suggested that the new ELISA has good distinguishing power and sensitivity for diagnosing glioma patients. This is the first ELISA assay developed for an autoantibody of a glioma antigen and may prove valuable for the clinical detection of glioma.

How Relevant are GFAP Autoantibodies in Autism and Tourette Syndrome?

Controversy exists over the role of autoantibodies to central nervous system antigens in autism and Tourette Syndrome. We investigated plasma autoantibody titers to glial fibrillary acidic protein (GFAP) in children with classic onset (33) and regressive onset (26) autism, controls (25, healthy age- and gender-matched) and individuals with Tourette Syndrome (24) by enzyme-linked immunosorbent assays. We found a significant difference in autoantibody titers to GFAP, not accounted for by age, between the Tourette (significantly lower) and regressive autism groups. However, no differences were found between: classic/regressive; classic/controls; classic/Tourette; regressive/controls; or controls/Tourette. Autoantibody responses against GFAP are unlikely to play a pathogenic role in autism or Tourette Syndrome.

Biochemical markers related to Alzheimer's dementia in serum and cerebrospinal fluid.

The diagnosis of Alzheimer's disease (AD) is currently based on clinical and neuropsychological examination. To date there is no blood test available that can discriminate dementia patients from healthy individuals. In the present paper, an overview of the current state of knowledge on biologic markers in serum (plasma) and CSF is presented. The combination of characteristic plaque markers tau and amyloid bèta may constitute a specific and sensitive CSF marker for AD. Glial fibrillary acidic protein and antibodies in CSF may be a marker for severe neurodegeneration. CSF concentrations of the oxidative stress markers 3-nitrotyrosine, 8-hydroxy-2'-deoxyguanosine and isoprostanes are increased in AD patients. Serum 24S-OH-cholesterol may be an early whereas glial fibrillary acidic protein autoantibody level may be a late marker for neurodegeneration. To date, serum alpha(1)-Antichymotripsin concentration is the most convincing marker for CNS inflammation. Increased serum homocysteine concentrations have also been consistently reported in AD. In summary, a large overlap in mean concentrations has been observed in studies comparing AD patients with healthy controls for single markers. These studies together support the theory of testing several serum markers in combination for the diagnosis of AD.