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Serological biomarkers in autoimmune GFAP astrocytopathy.

ABSTRACT: Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a newly defined meningoencephalomyelitis. The pathogenesis of GFAP-A is not well understood. The present study measured the expression levels of 200 serological cytokines in GFAP-A patients, NMOSD patients and healthy controls (HCs). The correlations between serum cytokine levels and clinical information in GFAP-A patients were analyzed. A total of 147 serological proteins were differentially expressed in GFAP-A patients compared to HCs, and 33 of these proteins were not observed in NMOSD patients. Serum levels of EG-VEGF negatively correlated with GFAP antibody titers, MIP-3 alpha positively correlated with clinical severity in GFAP-A patients, and LIGHT positively correlated with WBC counts and protein levels in the CSF of GFAP-A patients. These results suggest that GFAP and AQP4 astrocytopathy share some common pathology related to TNF signaling. Serum MIP 3 alpha may be a biomarker to assess clinical severity and a potential target for therapy of autoimmune GFAP astrocytopathy.

SUBMITTER: Fu CC

PROVIDER: S-EPMC9378990 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Serological biomarkers in autoimmune GFAP astrocytopathy.

Fu Cong-Cong CC Huang Lu L Xu Lu-Fen LF Jiang Li-Hong LH Li Hui-Lu HL Liao Sha S Yue Jiajia J Lian Chun C Yang Xin-Guang XG Long You-Ming YM

Frontiers in immunology 20220802

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a newly defined meningoencephalomyelitis. The pathogenesis of GFAP-A is not well understood. The present study measured the expression levels of 200 serological cytokines in GFAP-A patients, NMOSD patients and healthy controls (HCs). The correlations between serum cytokine levels and clinical information in GFAP-A patients were analyzed. A total of 147 serological proteins were differentially expressed in GFAP-A patients compa ...[more]

PMID: 35983033

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Project description:ObjectiveThe objective of this study is to investigate the presence of astrocyte antibodies in patients, excluding aquaporin-4 or glial fibrillary acidic protein (GFAP) antibodies, while evaluating associated biomarkers and pathologies.MethodsPatient serum and cerebrospinal fluid (CSF) were tested for antibodies using tissue- and cell-based assays. Neurofilament light chain (NFL) and GFAP in the CSF were detected using single-molecule array (SIMOA).Results116 patients accepted SIMOA. Fifteen functional neurological disorders patients without antibodies were designated as controls. Thirty-five patients were positive for astrocyte antibodies (Anti-GFAP: 7; Anti-AQP4: 7; unknown antibodies: 21, designed as the double-negative group, DNAP). The most frequent phenotype of DNAP was encephalitis (42.9%), followed by myelitis (23.8%), movement disorders (19.0%), and amyotrophic lateral sclerosis-like (ALS-like) disease (14.2%). The levels of CSF GFAP and NFL in DNAP were higher than in the control (GFAP: 1967.29 [776.60-13214.47] vs 475.38 [16.80-943.60] pg/mL, p < 0.001; NFL: 549.11 [162.08-2462.61] vs 214.18 [81.60-349.60] pg/mL, p = 0.002). GFAP levels decreased in DNAP (n = 5) after immunotherapy (2446.75 [1583.45-6277.33] vs 1380.46 [272.16-2005.80] pg/mL, p = 0.043), while there was no difference in NFL levels (2273.78 [162.08-2462.61] vs 890.42 [645.06-3168.06] pg/mL, p = 0.893). Two brain biopsy patterns were observed: one exhibited prominent tissue proliferation and hypertrophic astrocytes, with local loss of astrocytes, while the other showed severe astrocyte depletion with loss of neurofilaments around the vessels. Eighteen patients received immunotherapy, and improved except one with ALS-like symptoms. We identified anti-vimentin in this patient.DiscussionThere are unidentified astrocyte antibodies. The manifestations of double-negativity are heterogeneous; nevertheless, the pathology and biomarkers remain consistent with astrocytopathy. Immunotherapy is effective.

Project description:Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a recently discovered autoimmune inflammatory disease of the central nervous system. It presents with a variety of clinical symptoms, including fever, seizures, psychiatric symptoms, limber weakness, and sensory symptoms. However, the symptoms of sleep disorders have not been sufficiently addressed. Here, we report a case of GFAP-A in which the patient complained of excessive daytime sleepiness and an excessive need for sleep. Our patient was a 58-year-old male who experienced excessive daytime sleepiness for 50 days following SARS-CoV-2 infection. He was diagnosed with coronavirus disease 2019 on June 1st. On the 7th of June, he experienced excessive daytime sleepiness, nausea, reduced food intake, lower limb weakness, and dysuria. Subsequently, his sleepiness significantly deteriorated on July 21st. Five months prior, the patient underwent laparoscopic partial right nephrectomy for clear-cell renal cell carcinoma. Brain MRI revealed abnormal hyperintense lesions in the pontine brain and around the mesencephalic aqueduct on T2 and T2-fluid attenuated inversion recovery (T2-FLAIR) sequences However, these lesions did not exhibit any pathological enhancement. Spinal cord MRI revealed lesions in the C6-C7 and T2-T3 segments on the T2 sequence. His Epworth Sleepiness Scale (ESS) score was 16 (reference range, <10), and 24-hour polysomnography supported the diagnosis of rapid-eye-movement sleep disorder and severe sleep apnea-hypopnea syndrome. Glial fibrillary acidic protein IgG antibodies were detected in the cerebrospinal fluid (1:32, cell-based assay) but not in the serum. The level of hypocretin in the cerebrospinal fluid was 29.92 pg/mL (reference range ≥110 pg/mL), suggesting narcolepsy type 1. After treatment with corticosteroids for approximately 1 month, the patient showed considerable clinical and radiological improvement, as well as an increase in hypocretin levels. Although repeated polysomnography and multiple sleep latency tests suggested narcolepsy, his ESS score decreased to 8. Our findings broaden the range of clinical manifestations associated with GFAP-A, thereby enhancing diagnostic and therapeutic strategies for this disease. Additionally, our results indicate a potential common autoimmune mechanism involving GFAP-A and orexin system dysregulation, warranting further investigation.

Project description:ObjectiveAutoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a novel steroid sensitive autoimmune disease, without a diagnostic consensus. The purpose of this study was to improve early GFAP-A diagnosis by increasing awareness of key clinical characteristics and imaging manifestations.MethodsMedical records of 13 patients with anti-GFAP antibodies in serum or cerebrospinal fluid (CSF) were reviewed for cross-sectional and longitudinal analysis of clinical and magnetic resonance imaging (MRI) findings.ResultsThe predominant GFAP-A clinical manifestations are limb weakness/numbness and fever. GFAP-A has a propensity in the early stage for meningeal and leptomeningeal lesions on the brainstem surface, with a typical pattern of periventricular linear radial and leptomeningeal enhancement. The clinical manifestations and leptomeningeal enhancement were rapidly alleviated after treatment with high doses of corticosteroids or/and intravenous immunoglobulin, although, there are patients who may present with increased brain parenchymal lesions. On 3T MRI, the spinal cord demonstrated extensive longitudinal T2-weighted hyper-intensity, central distribution, and gray matter involvement. Optic nerve involvement in some patients was also noted with optic nerve swelling and abnormal enhancement. In addition to the classic reversible splenium of corpus callosum syndrome (type I), this study found the much rarer type II with diffusion restriction on DWI (Diffusion Weighted Imaging) in the corpus callosum. Positive anti-GFAP antibodies in serum or cerebrospinal fluid (CSF) are important for GFAP-A diagnosis with overlapping antibodies commonly noted. This study found anti-GM3 antibodies, a rare finding also previously reported.ConclusionThis study correlates GFAP-A clinical and imaging features, noting a "delay" phenomenon between clinical manifestations, treatment response, and radiographic MRI findings. MRI T2-FLAIR brainstem hyperintensity and T2-FLAIR gadolinium enhanced images, and subtraction techniques were valuable for early lesion detection and accurate diagnosis.

Project description:BackgroundThe phenotype of peripheral neuropathy (PN) associated with glial fibrillary acidic protein-immunoglobulin G (GFAP-IgG) has not been well described.ObjectivesThe aim of this study was to report the frequency, clinical, and electrophysiological characteristics of PN in GFAP-IgG-positive patients.DesignThis study is a single-center retrospective observational study.Data sources and methodsGFAP-IgG-positive patients with PN were retrospectively identified from the Huashan Hospital Autoimmune Encephalitis Cohort between 2017 and 2021. Eight patients who presented with PN from other published studies were also included in the analysis. The clinical and electrophysiological characteristics of GFAP-IgG-related PN were described.ResultsA total of 21 (31%) patients (7 females, 14 males; M age: 42 ± 16 years) from a cohort of 68 GFAP-IgG-positive patients presented with PN. Twenty of 21 patients had symmetrical weakness. Sensory and autonomic symptoms were present in 16 and 15 patients, respectively. Lower extremities were the most frequently involved regions for both motor (20/21) and sensory (15/21) symptoms. Moreover, 13 patients (4 females, 9 males; M age: 43 ± 13 years) had electrodiagnostic study data, and 12 of 13 patients had abnormal findings. Regarding clinical features, motor nerve fibers were predominantly involved (12/13), and symmetric lower extremities (12/13) were the most commonly affected regions. Axonal neuropathy is the typical underlying pathophysiologic process of PN. All 21 patients responded to immunotherapy. However, four patients with tetraplegia had poor outcomes, and PN was the major determinant of their long-term disability. Most cases (6/8) from the literature presented with similar clinical and electrophysiological features to those from our cohort.ConclusionPeripheral nerves could be involved in autoimmune GFAP astrocytopathy. Predominant motor axonal neuropathy mainly involving the lower extremities is the most common PN phenotype in this disorder. GFAP-IgG-related PN is responsive to immunotherapy.RegistrationChinese Clinical Trial Registry: ChiCTR2000029115 (http://www.chictr.org).

Project description:BackgroundWe examined spatial patterns of brain atrophy after mild, moderate, and severe traumatic brain injury (TBI), the relationship between progression of brain atrophy with initial traumatic axonal injury (TAI), cognitive outcome, and with serum biomarkers of brain injury.MethodsA total of 143 patients with TBI and 43 controls were studied cross-sectionally and longitudinally up to 5 years with multiple assessments, which included brain magnetic resonance imaging, cognitive testing, and serum biomarkers.ResultsTBI patients showed progressive volume loss regardless of injury severity over several years, and TAI was independently associated with accelerated brain atrophy. Cognitive performance improved over time. Higher baseline serum neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were associated with greater rate of brain atrophy over 5 years.DiscusssionSpatial patterns of atrophy differ by injury severity and TAI is associated with the progression of brain atrophy. Serum NfL and GFAP show promise as non-invasive prognostic biomarkers of progressive neurodegeneration in TBI.HighlightsIn this longitudinal study of patient with mild, moderate, and severe traumatic brain injury (TBI) who were assessed with paired magnetic resonance imaging (MRI), blood biomarkers, and cognitive assessments, we found that brain atrophy after TBI is progressive and continues for many years even after a mild head trauma without signs of brain injury on conventional MRI. We found that spatial pattern of brain atrophy differs between mild, moderate, and severe TBI, where in patients with mild TBI , atrophy is mainly seen in the gray matter, while in those with moderate to severe brain injury atrophy is predominantly seen in the subcortical gray matter and whiter matter. Cognitive performance improves over time after a TBI. Serum measures of neurofilament light or glial fibrillary acidic protein are associated with progression of brain atrophy after TBI.

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Serological biomarkers in autoimmune GFAP astrocytopathy.

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Serological biomarkers in autoimmune GFAP astrocytopathy.

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