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Mashup Score: 21Resident Memory-like CD8+ T Cells Are Involved in Chronic Inflammatory and Neurodegenerative Diseases in the CNS - 6 month(s) ago
Background and Objectives Resident memory T (Trm) cells are a unique population that can survive and function in a compartmentalized tissue with inflammatory potential. We aim to investigate the alteration of Trm population in acute/chronic inflammatory and neurodegenerative diseases in the CNS. Methods The frequencies of CD4+ and CD8+ T cells expressing both CD69 and CD103, the markers for Trm cells, were quantified in the peripheral blood and CSF (n = 80 and 44, respectively) in a cross-sectional manner. The transcriptional profile of Trm-like population in the CSF was further analyzed using a public single-cell dataset. Results The frequency of CD69+CD103+CD8+ T cells was strikingly higher in the CSF than in the peripheral blood (among memory fraction, 13.5% vs 0.11%, difference (mean [SE]): 13.4% [2.9]). This CD69+CD103+CD8+ T-cell population was increased in the CSF from patients with chronic inflammatory diseases including multiple sclerosis and with neurodegenerative diseases su
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Mashup Score: 76
Objectives To assess the frequency and types of neuronal and glial (neural) antibodies in children with suspected autoimmune encephalitis (AE). Methods Patients younger than 18 years with suspected AE other than acute disseminated encephalomyelitis, whose serum or CSF samples were examined in our center between January 1, 2011, and April 30, 2022, were included in this study. Samples were systematically examined using brain immunohistochemistry; positive immunostaining was further investigated with cell-based assays (CBA), immunoblot, or live neuronal immunofluorescence. Results Of 2,750 children, serum or CSF samples of 542 (20%) showed brain immunoreactivity, mostly (>90%) against neural cell surface antigens, and 19 had antibodies only identified by CBA. The most frequent targets were N-methyl-d-aspartate receptor (NMDAR, 76%) and myelin oligodendrocyte glycoprotein (MOG, 5%), followed by glutamic acid decarboxylase 65 (2%) and γ-aminobutyric acid A receptor (2%). Antibodies against
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Mashup Score: 15Peptides From the Variable Domain of Immunoglobulin G as Biomarkers in Chronic Inflammatory Demyelinating Polyradiculoneuropathy - 6 month(s) ago
Background and Objectives Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinically heterogeneous immune-mediated disease. Diagnostic biomarkers for CIDP are currently lacking. Peptides derived from the variable domain of circulating immunoglobulin G (IgG) have earlier been shown to be shared among patients with the same immunologic disease. Because humoral immune factors are hypothesized to be involved in the pathogenesis of CIDP, we evaluated IgG variable domain–derived peptides as diagnostic biomarkers in CIDP (primary objective) and whether IgG-derived peptides could cluster objective clinical entities in CIDP (secondary objective). Methods IgG-derived peptides were determined in prospectively collected sera of patients with CIDP and neurologic controls by means of mass spectrometry. Peptides of interest were selected through statistical analysis in a discovery cohort followed by sequence determination and confirmation. Diagnostic performance was evaluated fo
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Mashup Score: 70
Objectives We describe 2 patients with glial fibrillary acidic protein (GFAP) autoimmunity secondary to aseptic viral meningitis or meningoencephalomyelitis. Methods This study involved a retrospective chart review. Results Two female patients, 45 and 55 years of age, developed aseptic meningoencephalomyelitis or meningitis; in one patient, it was likely caused by herpes simplex virus 2. The patients were recovering from the infectious condition when they, 51 and 5 days after onset, had new symptoms with detection of GFAP antibodies in the CSF; CSF and serum samples from the initial lumbar punctures had been negative for GFAP antibodies. Both patients recovered with steroid treatment (in one case, plus rituximab; in the other, plus azathioprine) including resolution of MRI and CSF abnormalities. Discussion These 2 patients had GFAP autoimmunity secondary to viral meningoencephalomyelitis or meningitis. This suggests that GFAP astrocytopathy might not always be a primary disease entity;
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Mashup Score: 90Increased Intracranial Pressure in Pediatric Myelin Oligodendrocyte Glycoprotein Antibody–Associated Disease - 7 month(s) ago
Background and Objectives Elevated intracranial pressure (ICP) in myelin oligodendrocyte glycoprotein (MOG) antibody–associated disease (MOGAD) has been largely unexplored. The objectives of this study were to determine the frequency of increased ICP in MOGAD and its association with disease course and outcomes and to highlight cases requiring medical and/or surgical management of increased ICP. Methods In this retrospective, single-center cohort study, we examined the clinical and paraclinical data from the initial presentation and follow-up data of children diagnosed with MOGAD. In those with opening pressure (OP) measurements, univariate analyses were used to evaluate factors associated with increased ICP, which was defined as OP > 28 cm H2O. We also present a case series of patients with or without OP measurement who required medical and/or surgical management of increased ICP. Results Of 86 children with MOGAD, 43 (50.0%) had an OP recorded and 7 (8.1%) required ICP management. In
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This single-center cohort study of pediatric #MOGAD describes the frequency of increased intracranial pressure using lumbar puncture opening pressure measurements and evaluates its association with disease course and outcome. Read the open access article: https://t.co/gXclQ3EfDN https://t.co/puRF4gyB4e
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Mashup Score: 36Immune Checkpoint Inhibition–Related Myasthenia-Myositis-Myocarditis Responsive to Complement Blockade - 7 month(s) ago
Objective Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but come with immune-related adverse events (irAEs) that provide a novel challenge for treating physicians. Neuromuscular irAEs, including myositis, myasthenia gravis (MG), and demyelinating polyradiculoneuropathy, lead to significant morbidity and mortality. Methods We present a case of severe myasthenia-myositis-myocarditis overlap in a patient receiving ICIs for breast cancer. Clinical findings were recorded. Results A 47-year-old woman developed tetraparesis, dysphagia, and muscle pain during ICI treatment. MG with a thymoma had been diagnosed earlier. Neuromuscular overlap irAEs with cardiac affection was confirmed, and ICI treatment was discontinued. Given a lack of clinical response to standard therapies, a muscle biopsy was performed demonstrating complement deposition. Eculizumab treatment led to rapid improvement in muscle strength and cardiac function. Discussion Neuromuscular irAEs are associat
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Mashup Score: 68Antibody-Negative Autoimmune Encephalitis - 7 month(s) ago
Background and Objectives Autoimmune encephalitis (AE) refers to a heterogenous group of inflammatory CNS diseases. Subgroups with specified neural autoantibodies are more homogeneous in presentation, trigger factors, outcome, and response to therapy. However, a considerable fraction of patients has AE features but does not harbor detectable autoantibodies and is referred to as antibody-negative AE. Our aim was to describe clinical features, trigger factors, treatments, and outcome of a cohort of comprehensively tested antibody-negative AE patients. Methods This retrospective monocentric study recruited adult patients whose serum and/or CSF was sent to our tertiary center for neural antibody testing between 2011 and 2020, who entered the diagnostic algorithm as possible antibody-negative AE and had the following: (1) probable antibody-negative AE, definite antibody-negative acute disseminated encephalomyelitis (ADEM), or definite autoimmune limbic encephalitis (LE) according to diagnos
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This study outlines the clinical presentation of antibody-negative autoimmune encephalitis (AE), warns of the considerable mortality, and highlights the importance of comprehensive antibody testing in cases with suspected antibody-negative AE. Learn more: https://t.co/zLgawU1PqO https://t.co/lk9QbIw9hW
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Mashup Score: 29Long-term Effects of IL-6 Receptor Blockade Therapy on Regulatory Lymphocytes and Neutrophils in Neuromyelitis Optica Spectrum Disorder - 7 month(s) ago
Background and Objectives Neuromyelitis optica spectrum disorder (NMOSD) is a disabling autoimmune neurologic disease. Anti–IL-6 receptor (IL-6R) therapy prevents relapses in patients with anti–aquaporin 4 (AQP4)-IgG-positive NMOSD; however, it remains unclear how cellular immune components are altered by anti–IL-6R therapy. In this study, we examined the long-term effects of the anti–IL-6R monoclonal antibody tocilizumab (TCZ) on immune cell profiles in patients with NMOSD. Methods Monthly IV injections of TCZ (8 mg/kg) were administered as an add-on therapy to 19 anti–AQP4-IgG-positive patients, who had been refractory to corticosteroids and immunosuppressive drugs. Peripheral blood was collected before infusion of TCZ for flow cytometry analysis of lymphocyte subsets. Seven patients provided whole blood samples for gene expression profiles. Results Patients with NMOSD had reduced numbers of lymphocyte subsets with regulatory functions, including transitional B cells, CD56high NK cel
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Mashup Score: 56Chronic Enterovirus Meningoencephalitis in Prolonged B-Cell Depletion After Rituximab Therapy - 7 month(s) ago
Objectives Persistent impaired immunity is possible even years after B-cell depleting therapies. This may favor the occurrence of infections, including infectious meningitis and encephalitis. In this study, we report a case of chronic enterovirus meningoencephalitis in prolonged B-cell depletion years after rituximab therapy. Methods This is a case report from a German academic hospital. In addition to repeated clinical examinations, repeated brain MRI and extended CSF and laboratory diagnostics were performed. We used the CARE checklist when writing our report. Results A 38-year-old man presented with high fever (>40°C), severe headache, and progressive neurologic and cognitive deficits. As result of previous lymphoma therapy with rituximab years ago, prolonged B-cell aplasia was detected. To restore humoral immunity, the patient received repeated infusions of immunoglobulins. In the end, a complete restitution of the physical and mental condition was achieved with the established the
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Mashup Score: 1mRNA COVID-19 Vaccination Does Not Exacerbate Symptoms or Trigger Neural Antibody Responses in Multiple Sclerosis - 8 month(s) ago
Background and Objective In people with multiple sclerosis (pwMS), concern for potential disease exacerbation or triggering of other autoimmune disorders contributes to vaccine hesitancy. We assessed the humoral and T-cell responses to SARS-CoV-2 after mRNA vaccination, changes in disease activity, and development of antibodies against central or peripheral nervous system antigens. Methods This was a prospective 1-year longitudinal observational study of pwMS and a control group of patients with other inflammatory neurologic disorders (OIND) who received an mRNA vaccine. Blood samples were obtained before the first dose (T1), 1 month after the first dose (T2), 1 month after the second dose (T3), and 6 (T4), 9 (T5), and 12 (T6) months after the first dose. Patients were assessed for the immune-specific response, annualized relapse rate (ARR), and antibodies to onconeuronal, neural surface, glial, ganglioside, and nodo-paranodal antigens. Results Among 454 patients studied, 390 had MS (2
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This study found that an increase in CD69+CD103+CD8+ resident memory-like T cell population in the CSF is related with both chronic neuroinflammatory & some neurodegenerative diseases in the CNS, suggesting a partially shared pathology in these diseases. https://t.co/DWMNZ2ahcy https://t.co/jFX9Mmue45