Glial Fibrillary Acidic Protein Antibodies Research Articles

Comparative Brain Microanatomical and Neurochemical Alterations Following the Administration of Seven Oral Artemisinin-Based Combination Therapies in Swiss Mice

Over a decade after artemisinin-based combination therapy (ACT) approval as the most preferred anti-malarial drug. Seven ACTs can be sourced as over-the-counter medications in most African pharmacies without prescription. A comparative neurotoxicity of these ACTs was investigated in an in vivo experimental model. Swiss mice numbering 40, weighing 18 - 26 g were allotted to eight groups (n = 5). Group 1 (normal control [NC]), received distilled water 10 mL, while groups 2 to 8 were administered (5.71 mg artesunate+amodiaquine [AA]); (19.29 mg artesunate+mefloquine [AM]); (10.36 mg artesunate+sulfadoxine+pyrimethamine [ASP]); (19.29 mg artesunate+pyronaridine [APy]); (12.5 mg artemisinin+piperaquine [AP]); (15.42 mg dihydroartemisinin+piperaquine [DP]); and (8 mg artemether+lumefantrine [AL]) per kg body weights, respectively orally for 3 days, but for 2 days in group 6. Animals were sacrificed 24 hrs after last administration under ketamine anaesthesia (100 mg/kg, i.p), and excised brains were evaluated for neurochemical and neurohistological alterations. Oxidative stress markers: malondialdehyde and reduced glutathione significantly (p < 0.05) increased as well as antioxidant enzymes glutathione peroxidase, catalase, superoxide dismutase in ACT-administered groups compared to NC. Neurohistology of hippocampal cornu ammonis 1 (CA1) and cerebellum demonstrated vacuolations, neuronal hypertrophy and atrophy pyramidal, and Purkinje neurons. Immunohistochemistry with glial fibrillary acidic protein antibody demonstrated mild to mostly severe astrogliosis in the ACT-administered groups. In conclusion, oxidative stress markers and antioxidants were elevated in the order DP>APy>AP>ASP>AA>AL>AM. Together with the neurohistology, neurotoxicity were in the order DP>ASP>APy>AP>AL>AA>AM particularly in the hippocampus compared to the cerebellum. KEYWORDS: Artemisinin-based combination therapies, Cerebellum, CA1 region of the hippocampus, Neurodegeneration, Oxidative stress.

A case of autoimmune glial fibrillary acidic protein astrocytopathy with various symptoms such as optic disc edema and cerebellar ataxia

A 59-year-old man had developed visual abnormality, nausea, headache, and weight loss since three months before. The ophthalmologist found severe optic disc edema in both eyes, and referred him to our hospital. The patient had mild cerebellar ataxia. Increased cerebrospinal fluid pressure, increased protein and cell counts, positive oligoclonal band, and contrast-enhanced head MRI showed multiple linear perivascular radial gadolinium enhancement around bilateral lateral ventricles. His subjective and objective findings significantly improved with steroid treatment. The cerebrospinal fluid was found to be positive for glial fibrillary acidic protein (GFAP) antibodies, and a diagnosis of GFAP astrocytopathy was obtained. When optic edema or radial contrast effects was observed on contrast-enhanced MRI, GFAP astrocytopathy should be considerd. Prompt immunotherapy is required to circumvent the development of permanent visual impairment.

Clinical features and pathogenesis of Glial fibrillary acidic protein (GFAP) antibody-associated disorders

Glial fibrillary acidic protein (GFAP) antibody-associated disorders (AD) were recently proposed to be immune-mediated neurological disorders. The pathogenesis of GFAP antibody-AD is poorly understood. Pathologically, there is a marked infiltration of large numbers of lymphocytes, including CD8+ and CD4+ T cells, into the meningeal and brain parenchyma, especially around the perivascular areas. GFAP-specific cytotoxic T cells are considered to be the effector cells of GFAP antibody-AD. The common phenotype of GFAP antibody-AD includes meningoencephalitis with or without myelitis. During the clinical disease course, patients present with consciousness disturbances, urinary dysfunction, movement disorders, meningeal irritation, and cognitive dysfunction. The detection of GFAP antibodies in the cerebrospinal fluid (CSF) by cell-based assay is essential for a diagnosis of GFAP antibody-AD. The CSF can be examined for lymphocyte-predominant pleocytosis and elevated protein levels. Brain linear perivascular radial enhancement patterns are observed in about half of GFAP antibody-AD patients. Spinal cord magnetic resonance imaging is used to detect longitudinal extensive spinal cord lesions. Although corticosteroid therapy is generally effective, some patients have a poor prognosis and relapse.

A Mild Phenotype of Overlapping Syndrome With Myelin-Oligodendrocyte Glycoprotein and Glial Fibrillary Acidic Protein Immunoglobulin G: Mimicking Viral Meningitis in a Patient.

Glial fibrillary acidic protein (GFAP) astrocytopathy, an autoimmune central nervous system disorder characterized by the development of immunoglobulin G reactive with GFAP, has received growing attention in recent years. It is documented that GFAP-immunoglobulin G and other autoantibodies can be both detected in some patients. However, the coexistence of anti-myelin-oligodendrocyte glycoprotein (MOG) and GFAP antibodies is rarely reported. A 45-year-old man presented with headache, fever, backache, dysuria, tremble of hands, numbness of lower limbs, without diplopia, decreased vision, or other manifestations of optic neuritis. He was initially diagnosed with viral meningitis. After antiviral therapy, his headache, fever, and dysuria were improved, but the tremble of his upper limbs and numbness of his lower limbs still existed. A lumbar puncture was further performed and found both anti-GFAP and anti-MOG antibodies in the cerebrospinal fluid. No evidence of other immune disorders or infectious diseases was revealed. Meanwhile, a magnetic resonance scan showed enhancement of spinal pia mater in cervical, thoracic, and lumbar segments. He was then treated with immunoglobulin (intravenous immunoglobulin) therapy (25 g for 5 d), and steroid pulse therapy (methylprednisolone, 1 g for 5 d), followed by a gradual tapering of oral prednisolone. We reported a case of overlapping anti-GFAP and anti-MOG antibody-associated syndrome. This case enriches our understanding of the clinical manifestations of overlapping syndrome and expands the spectrum of this disorder.

COMPARISION OF THE GLIO-PROTECTIVE EFFECTS OF BIOPOLYMER COATED ELECTROSPUN SCAFFOLDS

Gliosis is a condition that plays a negative role in various neurological pathologies. In this study, it was aimed to obtain and compare the glio-protective effects of electrospun fibrous scaffolds coated by different biopolymers. First, in vitro gliosis model was obtained by inducing U-87 MG cells with LPS and IFN-γ. The optimized model was applied to U-87 MG cells grown on polycaprolactone (PCL), hyaluronic acid (HA) coated, gelatin coated, and collagen coated PCL scaffolds. Immunofluorescent (IF) staining was performed with glial fibrillary acidic protein (GFAP) antibody to determine the level of gliosis. It was found that 5µg/mL LPS concentration induced gliosis and hyaluronic acid-coated PCL scaffolds have shown a protective effect on gliosis.

Exploring Immunohistochemistry in Fish: Assessment of Antibody Reactivity by Western Immunoblotting.

In recent years, research on fish has seen remarkable advancements, especially in aquaculture, ornamental fish industry, and biomedical studies. Immunohistochemistry has become crucial in fish research, aiding in physiological and pathological investigations. However, the use of antibodies originally developed for mammals has raised concerns about their cross-reactivity and specificity in fish. This study systematically evaluated the reactivity of commonly used antibodies for diagnostic purposes, especially in fish pathology, including pan-cytokeratin, vimentin, S-100, glial fibrillary acidic protein, and desmin in the tissue of Sparus aurata, Dicentrarchus labrax, Oncorhynchus mykiss, and Carassius auratus. Western immunoblotting was employed to assess antibody specificity. The results revealed that the pan-cytokeratin and glial fibrillary acidic protein antibodies cross-react with all tested fish species, while S-100 demonstrated specific staining in sea bream, goldfish, and rainbow trout tissues. Conversely, vimentin and desmin antibodies displayed no reactivity. In conclusion, the anti-cytokeratin clone AE1/AE3 and the polyclonal rabbit anti-glial fibrillary acidic protein antibody, which are extensively used in mammals, were validated for fish immunohistochemical studies. Regrettably, D33 anti-desmin and V9 anti-vimentin clones are unsuitable for immunohistochemistry in the tested fish. These findings underscore the need for species-specific antibodies and proper validation for accurate immunohistochemistry analyses in fish research.

Peripheral nervous system involvement accompanies central nervous system involvement in anti-glial fibrillary acidic protein (GFAP) antibody-related disease.

Glial fibrillary acidic protein (GFAP) is expressed by astrocytes in the central nervous system (CNS), but also by immature and regenerative Schwann cells in the peripheral nervous system (PNS). GFAP antibodies (GFAP-Abs) in cerebrospinal fluid (CSF) have been mainly described in patients with meningoencephalomyelitis. We aimed to study PNS symptoms in patients with CSF GFAP-Abs. We retrospectively included all patients tested positive for GFAP-Abs in the CSF by immunohistochemistry and confirmed by cell-based assay expressing human GFAPα since 2017, from two French reference centers. In a cohort of 103 CSF GFAP-Abs patients, 25 (24%) presented with PNS involvement. Among them, the median age at onset was 48years and 14/25 (56%) were female. Abnormal electroneuromyography was observed in 11/25 patients (44%), including eight isolated radiculopathies, one radiculopathy associated with polyneuropathy, one radiculopathy associated with sensory neuronopathy, and one demyelinating polyradiculoneuropathy. Cranial nerve involvement was observed in 18/25 patients (72%). All patients except one had an associated CNS involvement. The first manifestation of the disease concerned the PNS in three patients. First-line immunotherapy was administered to 18/24 patients (75%). The last follow-up modified Rankin Scale was ≤ 2 in 19/23 patients (83%). Patients with PNS involvement had significantly more bladder dysfunction than patients with isolated CNS involvement (68 vs 40.3%, p = 0.031). PNS involvement in GFAP-Abs autoimmunity is heterogeneous but not rare and is mostly represented by acute or subacute cranial nerve injury and/or lower limb radiculopathy. Rarely, PNS involvement can be the first manifestation revealing the disease.

Identifying the building blocks for learning and memory in the carotid body

Glutamate is a major excitatory neurotransmitter with well-established roles for inducing neural plasticity, learning and memory in the central nervous system. In the carotid body, an organ derived in part from the neural crest, evidence suggests glutamatergic signalling is involved in its sensing of hypoxia. We hypothesized that altered glutamatergic signalling may underpin enhanced chemoreflex responses in carotid body in disease states. Therefore, we have initiated an investigation to assess the presence and location of glutamate receptors expressed in the carotid body of Wistar rats. We mined two independent RNA-sequencing (RNAseq) datasets to identify glutamate signalling components. Digital droplet PCR (ddPCR) was performed to validate the expression of selected glutamatergic target genes. Protein localisation was detailed using immunofluorescence and confocal microscopy in 12–16-week-old normotensive male Wistar rats. Neuronal phenotypes were identified using tyrosine hydroxylase (type I or glomus cells) and glial fibrillary acidic protein antibodies (type II cells). In carotid body extracts, RNAseq data revealed the presence of novel glutamatergic signalling components, not previously described. ddPCR analysis confirmed the expression of AMPA, NMDA and excitatory amino acid transporters. Glutamate ionotropic receptor AMPA type subunit 1 ( Gria1) showed co-localisation with the membrane of type I glomus cells. Glutamate ionotropic receptor NMDA type 1 ( Grin1) showed co-localisation with the nuclei membrane [JP1] of glomus cells. NMDA receptor type subunit 2C ( GRIN2C) showed co-localisation with the membranes of both glomus cells and type II cells. Expression of these receptors was not found on all glomus cells within a cluster suggesting functional heterogeneity within the carotid body. Synaptic Ras GTPase-activating protein 1 ( Syngap), a protein that interacts with glutamate synapses involved in learning, was expressed in both plasma and nuclear membranes of glomus cells. The excitatory amino acid transporter 5 ( EAAT5) showed co-localisation with both type I and type II cells. Additionally, we have observed that a local arterial injection of glutamate (via the internal carotid artery) evoked excitatory activity, followed by an inhibitory period as recorded from the carotid sinus nerve. Our results identified expression and location of glutamatergic AMPA and NMDA receptors in the carotid body[JP2]. We also found the presence of excitatory amino acid transporters, and proteins involved in chaperoning glutamate receptors for learning and memory, All told, we have identified the substrate for glutamate as a transmitter in the carotid body. Whether it plays a role in the learning and memory of carotid body function and/or sensitisation in disease remains to be elucidated. Funding: Health Research Council of New Zealand. Nothing to disclose. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Isolated optic neuritis with positive glial fibrillary acidic protein antibody

Background and objectivesAutoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) has been reported as a spectrum of autoimmune, inflammatory central nervous system disorders. Linear perivascular radial gadolinium enhancement patterns on brain magnetic resonance imaging (MRI) are a hallmark of these disorders. GFAP-A is associated with cerebrospinal fluid (CSF) GFAP antibody (GFAP-Ab), while the association with serum GFAP-Ab is less clear. This study aimed to observe the clinical characteristic and MRI changes of GFAP-Ab-positive optic neuritis (ON).MethodsWe performed a retrospective, observational case study at the department of neurology, Beijing Tongren Hospital, from December 2020 to December 2021. The serum of 43 patients and CSF samples of 38 patients with ON were tested for GFAP-Ab by cell-based indirect immune-fluorescence test.ResultsFour patients (9.3%) were detected GFAP-Ab positive, and in three out of the four patients, GFAP-Abs were detected only in serum. All of them demonstrated unilateral optic neuritis. Three patients (1, 2, and 4) experienced severe visual loss (best corrected visual acuity ≤ 0.1). Two patients (2 and 4) had experienced more than one episode of ON at the time of sampling. MRI showed optic nerve hyperintensity on T2 FLAIR images in all GFAP-Ab positive patients, and orbital section involvement was the most common. During follow-up (mean 4.5 ± 1 months), only Patient 1 had a recurrent ON, and no patient developed new other neurological events or systemic symptoms.ConclusionGFAP-Ab is rare in patients with ON and may manifest as isolated, relapsing ON. This supports the notion that the GFAP-A spectrum should comprise isolated ON.

Clinical features and biomarkers of acute encephalitis with claustrum sign (P5-5.027)

<h3>Objective:</h3> To determine clinical features and biomarkers of acute encephalitis with claustrum sign on brain MRI and to clarify the pathogenetic mechanism. <h3>Background:</h3> The claustrum sign has been described as reversible bilateral claustrum MRI hyperintensity on a T2-weighted MRI image. This finding has been reported in acute encephalitis, including acute necrotizing encephalopathy, febrile infection–related epilepsy syndrome, a subcategory of new-onset refractory status epilepticus. <h3>Design/Methods:</h3> We retrospectively analyzed the clinical features and cerebrospinal fluid (CSF) findings of three patients with acute encephalitis with claustrum sign. <h3>Results:</h3> All patients had prior symptoms suspected of infection, including fever, cough, and general fatigue. Two patients had meningeal signs and refractory status epilepticus. One patient had pyramidal signs and tremor. Claustrum sign was noted at 8, 28, and 52 days after the onset. In CSF, a glial fibrillary acidic protein (GFAP) antibody was detected in one patient with pyramidal signs and tremor. The other two patients had no antineuronal antibodies detected by tissue-based immunofluorescence assay using frozen rat brain sections. Compared with GFAP antibody-negative patients, GFAP antibody-positive patients had increased levels of CSF cell counts (antibody-positive vs antibody-negative; 127/μL vs 13 and 32/μL), protein concentrations (157 mg/dL vs 39 and 58 mg/dL), and tumor necrosis factor α (25.3 pg/mL vs 2.82 and 2.95 pg/mL). Interleukin 6 (IL-6) in CSF with GFAP antibody-negative patients was significantly higher than those with antibody-positive patients (195 and 609 pg/mL vs. 19.2 pg/mL). All patients required ventilator management and received immunotherapies. Two GFAP antibody-negative patients had improved, but a GFAP antibody-positive patient had died due to pneumonia. <h3>Conclusions:</h3> Acute encephalitis with claustrum sign is associated with at least increased levels of IL6 and GFAP antibody (i.e., GFAP astrocytopathy). In addition to CSF cytokine measurements, it is considered that GFAP antibody measurements should be performed in this disorder. <b>Disclosure:</b> Dr. Shimohata has nothing to disclose. Akira Takekoshi has nothing to disclose. Kimihiko Kaneko has nothing to disclose. Juichi Fujimori has nothing to disclose. Dr. Ioku has nothing to disclose. Keisuke Imai has nothing to disclose. Dr. Kimura has nothing to disclose.

GFAP astrocytopathy presenting after COVID-19 infection with meningoencephalomyelitis and good recovery with immunotherapy (P14-4.001)

<h3>Objective:</h3> To describe a case of post-COVID-19 GFAP astrocytopathy presenting with meningoencephalomyelitis. <h3>Background:</h3> Glial fibrillary acidic protein (GFAP) astrocytopathy is a newly described autoimmune disorder that presents with meningoencephalitis, myelitis and cerebellar dysfunction. Differential diagnosis includes inflammatory, neoplastic and infectious etiologies. GFAP astrocytopathy associated meningoencephalomyelitis is a rare, but treatable neurologic sequela of COVID-19. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 62-year-old man presented with progressive confusion, recurrent falls, and weight loss with initial symptom onset during COVID-19 infection 6 weeks prior. MRI showed patchy parenchymal and ependymal enhancement in the brainstem and temporal lobe as well as T2 hyperintensity throughout the cervical and thoracic cord consistent with transverse myelitis. Four lumbar punctures demonstrated elevated protein between 100–200 mg/dl and significant lymphocytic pleocytosis with 300–600 nucleated cells. Extensive infectious work-up was negative. Malignancy work-up showed PET-CT avidity in the spinal cord and positive MYD88 mutation in the CSF, possibly indicating a lymphoproliferative condition. However, CSF cytology, CSF flow cytometry and a bone marrow biopsy showed no evidence of malignancy on repeated testing. CSF autoimmune encephalopathy panel demonstrated high titers of GFAP antibodies. Initial treatment included pulse-dose steroids and IVIG with minimal improvement in cognition. He was then treated with pulse-dose steroids and rituximab with markedly improved cognition, motor function and appetite. Subsequent 2-month MRI demonstrated partial resolution of his cerebral and spinal lesions. <h3>Conclusions:</h3> Subacute meningoencephalitis, with or without myelitis, is a typical presentation of GFAP astrocytopathy. Other symptoms include ataxia, blurred vision with optic disc edema, dysautonomia, seizures, area postrema syndrome and psychiatric symptoms. Most patients have a steroid responsive monophasic course, but approximately 20% of patients have relapsing disease. GFAP astrocytopathy should be on the differential for meningoencephalomyelitis, especially with infectious prodrome, such as COVID-19 infection. Early recognition and treatment can lead to improvement of neurologic deficits and a good outcome. <b>Disclosure:</b> Dr. Song has nothing to disclose. Dr. Oetjen has nothing to disclose. Dr. Harrold has nothing to disclose. Dr. Dietrich has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Dietrich has received publishing royalties from a publication relating to health care. Kien-Ninh Ly has nothing to disclose. Dr. Venna has nothing to disclose.

Sudden Death in Autoimmune GFAP Astrocytopathy (P5-5.020)

<h3>Objective:</h3> To describe a rare fatal outcome in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. <h3>Background:</h3> Our patient was a 42 year old healthy woman who presented with 3 months of low back pain, bilateral upper extremity postural tremor, neck pain which progressed to 1 week of confusion and memory impairment. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> Neurologic exam revealed impaired attention, 3+ deep tendon reflexes throughout, bilateral upper extremity postural tremor and narrow based gait. MRI Brain showed abnormal, diffuse and relatively symmetric periventricular linear enhancement with associated subependymal enhancement. MRI C-spine demonstrated longitudinally extensive T2 FLAIR hyperintensity extending from C2–T2. Lumbar puncture showed opening pressure of 19 cm H2O with lymphocytic pleocytosis. She was treated with 5 days of pulse-dose corticosteroids with significant neurologic improvement and was discharged on prednisone taper. She was at her neurological baseline at Neuroimmunology clinic a week after the discharge. In the interim, CSF studies returned positive for GFAP antibody. Two weeks after the visit, she had new-onset word-finding difficulties, forgetfulness and intermittent staring spells. She was started on prednisone 60 mg daily and had repeat lumbar puncture at the office. Four to five hours after the lumbar puncture, she developed worsening confusion and bilateral upper extremity shaking. She was brought to our ED where her exam revealed dilated pupils with minimal reaction to light. CT head and CTA of the head and neck showed diffuse cerebral edema with absent cortical blood flow. Death by neurologic criteria was met the next day. <h3>Conclusions:</h3> Autoimmune GFAP astrocytopathy has an overall favorable prognosis. Our patient had a fatal outcome secondary to cerebral herniation following lumbar puncture, similar to the first reported fatal case. These two cases suggest that autoimmune GFAP astrocytopathy may present with diffuse cerebral edema and caution should be taken when performing lumbar punctures when this disease is suspected or diagnosed. <b>Disclosure:</b> Dr. Mahat has nothing to disclose. Dr. Dermigny has nothing to disclose. Dr. Alzyoud has nothing to disclose. Dr. Pilato has nothing to disclose.

Nanoporous Carbon Immunosensor for Highly Accurate and Sensitive Clinical Detection of Glial Fibrillary Acidic Protein in Traumatic Brain Injury, Stroke, and Spinal Cord Injury.

Elevated glial fibrillary acidic protein (GFAP) in the blood serum is one of the promising bodily fluid markers for the diagnosis of central nervous system (CNS) injuries, including traumatic brain injury (TBI), stroke, and spinal cord injury (SCI). However, accurate and point-of-care (POC) quantification of GFAP in clinical blood samples has been challenging and yet to be clinically validated against gold-standard assays and outcome practices. This work engineered and characterized a novel nanoporous carbon screen-printed electrode with significantly increased surface area and conductivity, as well as preserved stability and anti-fouling properties. This nano-decorated electrode was immobilized with the target GFAP antibody to create an ultrasensitive GFAP immunosensor and quantify GFAP levels in spiked samples and the serum of CNS injury patients. The immunosensor presented a dynamic detection range of 100 fg/mL to 10 ng/mL, a limit of detection of 86.6 fg/mL, and a sensitivity of 20.3 Ω mL/pg mm2 for detecting GFAP in the serum. Its clinical utility was demonstrated by the consistent and selective quantification of GFAP comparable to the ultrasensitive single-molecule array technology in 107 serum samples collected from TBI, stroke, and SCI patients. Comparing the diagnostic and prognostic performance of the immunosensor with the existing clinical paradigms confirms the immunosensor's accuracy as a potential complement to the existing imaging diagnostic modalities and presents a potential for rapid, accurate, cost-effective, and near real-time POC diagnosis and prognosis of CNS injuries.

Detection and significance of glial fibrillary acidic protein antibody in autoimmune astocytopathy and related diseases

: Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is an antibody-related astrocytic disease for which a specific GFAP antibody serves as a biological marker. Indeed, cerebral spinal fluid positive and/or seropositivity for GFAP is an important basis for its diagnosis. However, because patients with autoimmune encephalitis or demyelinating diseases can have a similar antibody profile, termed overlapping autoimmune syndrome, it remains a challenge for clinicians to diagnose and suitably classify autoimmune GFAP-A. To further understand the significance of GFAP antibody detection in neuroimmune diseases, this article discusses GFAP antibodies in autoimmune GFAP-A, progress for detection of GFAP antibodies, diagnostic significance of GFAP antibodies in prototypical disease, as well as overlapping syndrome.

Detection and significance of glial fibrillary acidic protein antibody in autoimmune astocytopathy and related diseases.

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is an antibody-related astrocytic disease for which a specific GFAP antibody serves as a biological marker. Indeed, cerebral spinal fluid positive and/or seropositivity for GFAP is an important basis for its diagnosis. However, because patients with autoimmune encephalitis or demyelinating diseases can have a similar antibody profile, termed overlapping autoimmune syndrome, it remains a challenge for clinicians to diagnose and suitably classify autoimmune GFAP-A. To further understand the significance of GFAP antibody detection in neuroimmune diseases, this article discusses GFAP antibodies in autoimmune GFAP-A, progress for detection of GFAP antibodies, diagnostic significance of GFAP antibodies in prototypical disease, as well as overlapping syndrome.

Duodenal alpha-Synuclein Pathology and Enteric Gliosis in Advanced Parkinson's Disease.

The role of the gut-brain axis has been recently highlighted as a major contributor to Parkinson's disease (PD) physiopathology, with numerous studies investigating bidirectional transmission of pathological protein aggregates, such as α-synuclein (αSyn). However, the extent and the characteristics of pathology in the enteric nervous system have not been fully investigated. We characterized αSyn alterations and glial responses in duodenum biopsies of patients with PD by employing topography-specific sampling and conformation-specific αSyn antibodies. We examined 18 patients with advanced PD who underwent Duodopa percutaneous endoscopic gastrostomy and jejunal tube procedure, 4 untreated patients with early PD (disease duration <5 years), and 18 age- and -sex-matched healthy control subjects undergoing routine diagnostic endoscopy. A mean of four duodenal wall biopsies were sampled from each patient. Immunohistochemistry was performed for anti-aggregated αSyn (5G4) and glial fibrillary acidic protein antibodies. Morphometrical semiquantitative analysis was performed to characterize αSyn-5G4+ and glial fibrillary acidic protein-positive density and size. Immunoreactivity for aggregated α-Syn was identified in all patients with PD (early and advanced) compared with controls. αSyn-5G4+ colocalized with neuronal marker β-III-tubulin. Evaluation of enteric glial cells demonstrated an increased size and density when compared with controls, suggesting reactive gliosis. We found evidence of synuclein pathology and gliosis in the duodenum of patients with PD, including early de novo cases. Future studies are required to evaluate how early in the disease process duodenal pathology occurs and its possible contribution to levodopa effect in chronic patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Glial fibrillary acidic protein astrocytopathy and tuberculous meningoencephalitis occurring in a patient with Legionella pneumonia: a case report

BackgroundAutoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a recently identified recurrent meningoencephalomyelitis with GFAP immunoglobulin G presence in the serum or cerebrospinal fluid (CSF) as a specific biomarker. GFAP astrocytopathy is closely associated with the occurrence of some tumors and often coexists with other antibodies, such as the N-methyl-D-aspartate receptor and aquaporin-4 antibodies. However, GFAP astrocytopathy complicated by central nervous system infection is rare.Case presentationHere, we present the case of a patient admitted to a local hospital due to a prominent fever and cough. The patient had a 1-month history of headaches before admission that were not considered serious at the time. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid revealed a high sequence number of Legionella pneumophila and a few mycobacteria. His cough and fever improved significantly after antibiotic treatment. Still, a slight headache remained. Subsequently, his condition worsened, and he visited our hospital with a disturbance of consciousness. Mycobacterium tuberculosis was detected with mNGS of the CSF, while the CSF and serum were also positive for GFAP antibodies. Following anti-tuberculosis and steroid therapy, the patient’s symptoms improved, and he tested negative for the GFAP antibody.ConclusionThis is the first reported case of GFAP astrocytopathy complicated by tuberculous meningoencephalitis. Due to overlaps in the clinical manifestations of the two diseases, GFAP astrocytopathy is sometimes misdiagnosed as tuberculous meningoencephalitis. Therefore, in addition to ensuring careful identification of the two diseases, clinicians need to be aware of their possible co-existence.

Clinical characteristic of myelin oligodendrocyte glycoprotein antibody associated cortical encephalitis in adults and outcomes following glucocorticoid therapy.

To describe the clinical and radiological features, as well as outcomes following glucocorticoid therapy and recurrence in adults suffering from cortical encephalitis associated with myelin oligodendrocyte glycoprotein (MOG) antibody. The clinical information of nine adult patients suffering from cortical encephalitis associated with MOG antibody admitted to the Affiliated Brain Hospital of Nanjing Medical University from 2020 to 2022 was systematically reviewed. The clinical symptoms, laboratory data, imaging results, outcomes following glucocorticoid therapy and recurrence were evaluated. A total of 9 patients positive for MOG antibody and suffering from cortical encephalitis were included in our study (55.6% men, median age 29 years, 15-57 years). The most common clinical symptoms included headache (77.8%), fever (66.7%), and generalized seizures (55.6%). Some patients also experienced limb shaking (22.2%), leg numbness (22.2%), transient motor aphasia (11.1%), and vision loss (11.1%). The main features of cerebrospinal fluid () examination were increased intracranial pressure, pleocytosis, and elevated cerebrospinal fluid (CSF) protein. In addition, N-methyl-D-aspartate receptor (NMDAR) and MOG antibodies were found in the CSF of 3 patients, and NMDAR, MOG, and glial fibrillary acidic protein antibodies were found in the CSF of 1 patient. All patients were subjected to magnetic resonance imaging (MRI) and the images of eight of them showed T2 and/flair image hyperintense lesions, three showed meningeal or lesion enhancement and four showed white matter lesions, which were mostly located in the midline structures (75%). All patients received glucocorticoid therapy in the acute phase and in remission, and eight of them received an intravenous high dose of methylprednisolone, including one patient who received a simultaneous immunoglobulin therapy. One patient was treated with low-dose prednisolone tablets. Seven (77.8%) patients were wholly recovered at discharge, and 2 (22.2%) patients were left with slight symptoms. During the median 9-month follow-up (range: 2-36 months), 2 (22.2%) patients developed recurrence. The clinical manifestations of adult MOG antibody-associated cortical encephalitis were significantly different from those of the typical MOG antibody-associated disease (MOGAD). Patients in the acute phase of the disease were prone to show signs similar to central nervous system infection, requiring clinicians to have the ability to recognize the disease to avoid misdiagnosis. In addition, seizures were common in MOG antibody-related encephalitis, and the type of seizures was age-related. Brain MRI results showed that the distribution of cerebral cortex lesions was closely related to the classification of cortical encephalitis. Based on the patient's response to the treatment, glucocorticoid therapy was effective against MOG antibody-associated cortical encephalitis, which is consistent with the treatment response and clinical prognosis of MOGAD. Therefore, our opinion was that MOG antibody might be the "responsible antibody" in MOG antibody-associated cortical encephalitis, although further studies are needed to confirm this hypothesis.

Ultrasensitive Determination of Glial-Fibrillary-Acidic-Protein (GFAP) in Human Serum-Matrix with a Label-Free Impedimetric Immunosensor

In this work, immobilizing anti-GFAP antibodies via covalent attachment onto L-cysteine/gold nanoparticles that were modified with screen-printed carbon electrodes (Anti-GFAP/L-cys/AuNps/SPCE) resulted in the development of a sensitive label-free impedance immunosensor for the detection of Glial Fibrillary Acidic Protein (GFAP). The immunosensor's stepwise construction was studied using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). L-cysteine was chosen as the linker between GFAP antibodies and Au NPs/SPCE because it enables the guided and stable immobilization of GFAP antibodies, thus resulting in increased immunosensor sensitivity. As a redox probe, 5 mM of [Fe(CN)6]3-/4- was used to measure the electron-transfer resistance (Ret), which was raised by the binding of antigens to the immobilized anti-GFAP on the surface of the modified electrode. A linear correlation between Rct and GFAP concentration was achieved under optimum conditions in the range of 1.0-1000.0 pg/mL, with an extraordinarily low detection limit of 51.0 fg/mL. The suggested immunosensor was successfully used to detect the presence of GFAP in human blood serum samples, yielding good findings. As a result, the proposed platform may be utilized to monitor central nervous system injuries.

Glial Fibrillary Acidic Protein (GFAP) Antibody-Associated Astrocytopathy in Systemic Sarcoidosis

Objective To report two cases of glial fibrillary acidic protein (GFAP) antibody-associated meningoencephalitis in patients with biopsy-proven systemic sarcoidosis. Background GFAP astrocytopathy is an autoimmune neurologic disease first defined in 2016. To our knowledge, no association with systemic sarcoidosis has been previously reported. Design/Methods Case Series Results Patient 1 is a 47-year-old woman with pre-existing pulmonary sarcoidosis treated with steroids and methotrexate with remission 6 years prior. She subsequently developed new-onset epilepsy, progressive ataxia and vertical diplopia. GFAP antibodies were positive in the cerebrospinal fluid (CSF) by cell-based assay (CBA). Body PET scan showed diffuse FDG avidity in her lungs, spleen, and lymph nodes, suggesting simultaneous reactivation of her systemic sarcoidosis. She was treated with steroids followed by infliximab with resolution of her symptoms. Patient 2 is a 58-year-old man with known pulmonary sarcoidosis, who was off immunosuppression at the time of his presentation but had received steroids 17 years prior. He presented with progressive apathy, memory disturbance, dysarthria, and gait instability. MRI revealed widespread T2 hyperintensities. GFAP antibodies were positive in CSF on CBA and confirmed by tissue-based immunofluorescence assay. He received steroids with initial response but relapsed after steroid discontinuation. He improved after restarting steroids and was subsequently transitioned to infliximab with sustained neurologic recovery. Conclusions Sarcoidosis is a poorly understood multi-system disorder that is presumably an immune-mediated response to yet unidentified antigen(s). It is known to co-exist with other autoimmune diseases, with autoimmune thyroiditis being most common. GFAP astrocytopathy is also poorly understood. GFAP is found intracellularly and similar to other antibody-mediated diseases against intracellular epitopes, the antibodies are believed to be a biomarker of underlying autoimmunity but not directly pathogenic. We report these cases to highlight a potential association between production of intrathecal GFAP antibodies and systemic sarcoidosis, which may provide insights into the pathogenesis of these two diseases.