Aquaporin-4 antibodies

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder characterized by relapses of inflammation and demyelination primarily affecting the optic nerve and the spinal cord. C5 complement inhibition is an effective therapeutic approach in the treatment of NMOSD. In this systematic review and meta-analysis, we aimed to determine the role of C5 inhibitors in the treatment of patients with seropositive anti-aquaporin-4 antibody (AQP4+IgG) NMOSD. METHODS: This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline...

A rapidly expanding repertoire of neural antibody biomarkers exists for autoimmune central nervous system disorders. Following clinical recognition of an autoimmune CNS disorder, the detection of a neural antibody facilitates diagnosis and informs prognosis and management. This review considers the phenotypes, diagnostic assay methodologies, and clinical utility of neural antibodies in autoimmune CNS disorders. Autoimmune CNS disorders may present with a diverse range of clinical features. Clinical phenotype should inform the neural antibodies selected for testing via the use of phenotype-specific panels...

Neuromyelitis optica spectrum disorder (NMOSD) is a rare demyelinating disease of the central nervous system primarily affecting the optic nerves, spinal cord, and brainstem. Viral infection may trigger NMOSD. Here, we report the case of a 34-year-old female presenting with a range of symptoms including nausea, vomiting, dysphagia, choking, and fatigue with unsteady gait, diplopia, hearing loss, left-sided facial paralysis, breathing difficulties, and hoarseness of voice. Her HBV DNA concentration, as determined by quantitative PCR analysis, exceeded 5×107 IU/ml in serum and 4...

We describe a patient with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) with unique features, including concurrent transverse myelitis. A 2-year-old previously healthy girl had clinical findings consistent with AESD, occurring in association with influenza A infection. The posterior brain regions were most severely affected, resulting in cortical blindness. She also developed bilateral limb weakness, and spine MRI revealed transverse myelitis in the cervical region. She was treated acutely with intravenous methylprednisolone...

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy caused by the autoantibody of aquaporin-4 (AQP4). Herein, we report a case of Tolosa-Hunt syndrome presenting with abducens palsy and AQP4 antibodies. This was a rare case of AQP4-immunoglobulin G seropositivity in a patient with Tolosa-Hunt syndrome. Our findings may expand the clinical phenotype of NMOSD and indicate that clinicians should consider testing for AQP4 antibodies in patients with Tolosa-Hunt syndrome.

BACKGROUND: Optic neuritis (ON) prognosis is influenced by various factors including attack severity, underlying aetiologies, treatments and consequences of previous episodes. This study, conducted on a large cohort of first ON episodes, aimed to identify unique prognostic factors for each ON subtype, while excluding any potential influence from pre-existing sequelae. METHODS: Patients experiencing their first ON episodes, with complete aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibody testing, and clinical data for applying multiple sclerosis (MS) diagnostic criteria, were enrolled...

BACKGROUND/AIM: With the popularity of endothelial keratoplasty (EK) procedures, Descemet membrane (DM) EK and pre-Descemet EK, considerable work has been done on understanding the posterior corneal anatomy. Most of the information available relates to the central cornea. We evaluated the peripheral cornea to explore the immunohistological and anatomical relationship between the pre-Descemet layer (PDL), DM and trabecular meshwork (TM). METHODS: Six donor human sclerocorneal discs were studied...

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy of the central nervous system, mediated by antibodies against aquaporin-4 water channel protein (AQP4-Abs), resulting in damage of astrocytes with subsequent demyelination and axonal damage. Extracellular communication through astrocyte-derived extracellular vesicles (ADEVs) has received growing interest in association with astrocytopathies. However, to what extent ADEVs contribute to NMOSD pathogenesis remains unclear. Here, through proteomic screening of patient-derived ADEVs, we observed an increase in apolipoprotein E (APOE)-rich ADEVs in patients with AQP4-Abs-positive NMOSD...

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an immune-mediated neuroinflammatory disease of the central nervous system. Patients typically present with sensory deficits, weakness, and incontinence. This is a case of a 43-year-old female with diabetes mellitus admitted for acute onset leg weakness and stool incontinence. Spinal MRI imaging revealed transverse myelitis, and her lab work was significant for an anti-aquaporin 4 (AQP4) antibody titer of 1:2,560. Initial treatment consisted of a high-dose steroid taper and plasmapheresis...

BACKGROUND: Anti-myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOGAD) is a type of acquired demyelinating disease that is distinct from multiple sclerosis (MS) and aquaporin-4 antibody neuromyelitis optica spectrum disorder (AQP4-NMOSD). Leptomeningeal enhancement (LME) has been reported in children and adults with MOGAD, and in adults with MS and AQP4-NMOSD, but less is known about LME in pediatric-onset MS (POMS) and pediatric AQP4-NMOSD. Here we compare the rates of LME in children with MOGAD, POMS, and AQP4-NMOSD...

Aquaporin Z (AqpZ), a bacterial water channel, forms a tetrameric complex and, like many other membrane proteins, activity is regulated by lipids. Various methods have been developed to facilitate structure determination of membrane proteins, such as the use of antibodies. Here, we graft onto AqpZ the ALFA tag (AqpZ-ALFA), an alpha helical epitope, to make use of the high-affinity anti-ALFA nanobody (nB). Native mass spectrometry reveals the AqpZ-ALFA fusion forms a stable, 1:1 complex with nB. Single-particle cryogenic electron microscopy studies reveal the octameric (AqpZ-ALFA)4 (nB)4 complex forms a dimeric assembly and the structure was determined to 1...

PURPOSE: To assess the retinal structural and microvascular change in aquaporin-4 antibody (AQP4) positive neuromyelitis optica spectrum disorder (NMOSD) patients and the correlation with clinical features. METHODS: A cross-sectional study was performed with optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) to measure retinal structure and microvascular parameters in AQP4 positive NMOSD patients. RESULTS: Sixty-two NMOSD patients (44 eyes with ON, NMOSD+ON; 77 eyes without ON, NMOSD-ON) and 62 healthy controls (HC, 124 eyes) were included...

PURPOSE: Despite mounting evidence indicating that aquaporin-4 antibody-positive optic neuritis (AQP4-ON) presents a less favorable prognosis than other types of optic neuritis, there exists substantial heterogeneity in the prognostic outcomes within the AQP4-ON cohort. Considering the persistent debate over the role of MRI in assessing the prognosis of optic neuritis, we aim to investigate the correlation between the MRI appearance and long-term visual prognosis in AQP4-ON patients. METHODS: We retrospectively reviewed the ophthalmological and imaging data of AQP4-ON patients admitted to our Neuro-ophthalmology Department from January 2015 to March 2018, with consecutive follow-up visits for a minimum of 3 years...

OBJECTIVE: To assess the pharmacokinetics and pharmacodynamics of the long-acting terminal complement 5 (C5) inhibitor ravulizumab in adults with anti-aquaporin-4 antibody-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) in the phase 3, open-label CHAMPION-NMOSD trial (NCT04201262). METHODS: Patients aged 18 years or older received a weight-based intravenous loading dose of ravulizumab (2,400-3,000 mg) on day 1, followed by weight-based maintenance doses (3,000-3,600 mg) on day 15 and once every 8 weeks thereafter...

OBJECTIVE: Aquaporin-4-antibody-seropositive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorder (MOGAD) are relapsing neuroinflammatory diseases, frequently leading to chronic pain. In both diseases, the spinal cord (SC) is often affected by myelitis attacks. We hypothesized that regional SC volumes differ between AQP4-IgG + NMOSD and MOGAD and that pain intensity is associated with lower SC volumes...

OBJECTIVES: Data on peripheral blood mononuclear cells (PBMCs) characteristics of aquaporin-4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are lacking. In this study, we describe the whole PBMCs landscape of the above diseases using cytometry by time-of-flight mass spectrometry (CyTOF). METHODS: The immune cell populations were phenotyped and clustered using CyTOF isolated from 27 AQP4-IgG seropositive NMOSD, 11 MOGAD patients, and 15 healthy individuals...

OBJECTIVE: Immune-mediated myelopathies are conditions in which the immune system attacks the spinal cord. This article describes the distinguishing characteristics of immune-mediated myelopathies and treatment strategies for patients affected by these disorders. LATEST DEVELOPMENTS: New biomarkers, such as aquaporin 4 and myelin oligodendrocyte glycoprotein antibodies, in the blood and spinal fluid have led to the identification of antigen-specific immune-mediated myelopathies and approved therapies to prevent disease progression...

OBJECTIVE: This article describes an integrative strategy to evaluate patients with suspected myelopathy, provides advice on diagnostic approach, and outlines the framework for the etiologic diagnosis of myelopathies. LATEST DEVELOPMENTS: Advances in diagnostic neuroimaging techniques of the spinal cord and improved understanding of the immune pathogenic mechanisms associated with spinal cord disorders have expanded the knowledge of inflammatory and noninflammatory myelopathies...

The influx of pathogenic aquaporin-4 antibodies (AQP4-Abs) across the blood-spinal cord barrier (BSCB) is crucial for the development and exacerbation of neuromyelitis optica (NMO). We examined whether prophylactic intravenous administration of anti-repulsive guidance molecule-a antibodies (RGMa-Abs) has disease-modifying effects on BSCB dysfunction using an NMO model elicited by peripheral administration of AQP4-Abs to rats. RGMa-Ab treatment attenuated the acute exacerbation of perivascular astrocytopathy in the spinal cord and clinical symptoms, which were highly correlated with neurofilament light chain levels in both the cerebrospinal fluid (CSF) and serum...

BACKGROUND Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSDs) are 2 similar but distinct diseases. These diseases were difficult to distinguish from each other until aquaporin-4-IgG (AQP-4-IgG) was discovered. The accurate identification of these 2 diseases is crucial for appropriate drug treatment in clinical practice. Herein, we report a case of AQP-4-IgG seroconversion with magnetic resonance imaging (MRI) findings suggestive of MS. CASE REPORT A 54-year-old woman developed weakness in her right lower extremity that gradually returned to normal 4 years ago...