Update in autoimmune and paraneoplastic myelopathies: Newly described antigen targets and antibody testing

Passeri, Michlene; Matthews, Elizabeth; Kammeyer, Ryan; Piquet, Amanda L.

doi:10.3389/fneur.2022.972143

Cited by 8 publications

(7 citation statements)

References 65 publications

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“…Another possibility is that AQP4-IgG is not the main pathogenic antibody but it might be induced by other underlying pathogenic antibody–antigen reactions. According to Passeri, some newly described auto-antibodies (GFAP-IgG, anti-collapsin response-mediator protein-5, anti-amphiphysin, anti-neuronal nuclear antibody-1, DPPX-IgG, GAD65-IgG, anti-Yo, anti-Ri, and others) can also mimic NMOSD ( 15 ). Unfortunately, only a few common antibodies were tested in our cases.…”

Section: Discussionmentioning

confidence: 99%

Neuromyelitis optica spectrum disorders associated with AQP4-positive-cancer—A case series

et al. 2022

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Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune, astrocytopathic diseases affecting the central nervous system(CNS), especially the central optic nerve and spinal cord. Aquaporin 4-immunoglobulin G (AQP4-IgG) is the dominant pathogenic antibody and can be detected in about 80% of patients with NMOSD. Although only a few cases were reported on NMOSD associated with cancer, they demonstrated the potential paraneoplastic link between cancer and NMOSD. In the present study, we report three NMOSD cases associated with cancer, which are teratoma and lung adenocarcinoma, teratoma, and transverse colon adenocarcinoma, respectively. Pathological staining of tumor sections revealed a high AQP4 expression. After tumor removal, all cases were stable and suffered no further relapses, which revealed the potential paraneoplastic mechanism between cancer and NMOSD. One of our patient's serum AQP4-IgG was transiently slightly elevated even though AQP4 was highly expressed in tumor cells, which indicates that AQP4 is not the main pathogenic antibody but might be induced by other underlying pathogenic antibody–antigen reactions.

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Section: Discussionmentioning

confidence: 99%

Neuromyelitis optica spectrum disorders associated with AQP4-positive-cancer—A case series

et al. 2022

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“…Blood and CSF laboratory studies are critical for establishing an accurate diagnosis of inflammatory myelopathy, not only for determining the role of inflammation as a pathogenic mechanism but also for providing a specific diagnosis in some types of myelitis. The discovery of specific pathogenic antibodies that target neural and glial antigens such as aquaporin 4, MOG, glial fibrillary acidic protein (GFAP), and other antigens linked to paraneoplastic disorders (eg, collapsin response mediator protein-5 [CRMP5]) [25][26][27] can be used as biomarkers of disease and define the subgroup of myelitis associated with autoimmune neurologic disorders. Testing of these autoantibodies should be centered on serologic studies rather than CSF because such autoantibodies are less frequent in CSF samples.…”

Section: Biomarkers In Autoimmune Inflammatory Myelopathiesmentioning

confidence: 99%

Clinical Approach to Myelopathy Diagnosis

Pardo

2024

CONTINUUM: Lifelong Learning in Neurology

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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 discovery of biomarkers of disease, such as anti–aquaporin 4 and anti–myelin oligodendrocyte glycoprotein antibodies involved in myelitis and other immune-related mechanisms, the emergence and identification of infectious disorders that target the spinal cord, and better recognition of myelopathies associated with vascular pathologies have expanded our knowledge about the broad clinical spectrum of myelopathies. ESSENTIAL POINTS Myelopathies include a group of inflammatory and noninflammatory disorders of the spinal cord that exhibit a wide variety of motor, sensory, gait, and sensory disturbances and produce major neurologic disability. Both inflammatory and noninflammatory myelopathies comprise a broad spectrum of pathophysiologic mechanisms and etiologic factors that lead to specific clinical features and presentations. Knowledge of the clinical variety of myelopathies and understanding of strategies for the precise diagnosis, identification of etiologic factors, and implementation of therapies can help improve outcomes.

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“…Autoimmune and paraneoplastic disorders targeting glia comprise a broad class of disease stimulated by autoreactive immune cells. 183 The autoantibodies involved in these disorders vary widely and result either in direct antibody-mediated toxicity or indirect T-cell-mediated autoimmunity. The clinical outcomes of these disorders also vary widely and can include demyelination and white matter loss (as well as cortical pathology) with psychosis, movement abnormalities, and cognitive difficulties.…”

Section: Astrocyte-targeted Autoimmune and Paraneoplastic Statesmentioning

confidence: 99%

“…Autoimmune and paraneoplastic disorders targeting glia comprise a broad class of disease stimulated by autoreactive immune cells 183 . The autoantibodies involved in these disorders vary widely and result either in direct antibody‐mediated toxicity or indirect T‐cell‐mediated autoimmunity.…”

Section: Astrocytic Dysfunction As the Basis For Neurobehavioral Diso...mentioning

confidence: 99%

“…The autoantibodies involved in these disorders vary widely and result either in direct antibody‐mediated toxicity or indirect T‐cell‐mediated autoimmunity. The clinical outcomes of these disorders also vary widely and can include demyelination and white matter loss (as well as cortical pathology) with psychosis, movement abnormalities, and cognitive difficulties 183 . While many autoimmune disorders directly target oligodendrocyte antigens—multiple sclerosis (MS) being prototypic—ample evidence now exists of both primary and paraneoplastic autoimmune disorders that directly target astrocytes.…”

Section: Astrocytic Dysfunction As the Basis For Neurobehavioral Diso...mentioning

confidence: 99%

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Astrocytes as master modulators of neural networks: Synaptic functions and disease‐associated dysfunction of astrocytes

Stogsdill

Harwell

Goldman

2023

Annals of the New York Academy of Sciences

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Astrocytes are the most abundant glial cell type in the central nervous system and are essential to the development, plasticity, and maintenance of neural circuits. Astrocytes are heterogeneous, with their diversity rooted in developmental programs modulated by the local brain environment. Astrocytes play integral roles in regulating and coordinating neural activity extending far beyond their metabolic support of neurons and other brain cell phenotypes. Both gray and white matter astrocytes occupy critical functional niches capable of modulating brain physiology on time scales slower than synaptic activity but faster than those adaptive responses requiring a structural change or adaptive myelination. Given their many associations and functional roles, it is not surprising that astrocytic dysfunction has been causally implicated in a broad set of neurodegenerative and neuropsychiatric disorders. In this review, we focus on recent discoveries concerning the contributions of astrocytes to the function of neural networks, with a dual focus on the contribution of astrocytes to synaptic development and maturation, and on their role in supporting myelin integrity, and hence conduction and its regulation. We then address the emerging roles of astrocytic dysfunction in disease pathogenesis and on potential strategies for targeting these cells for therapeutic purposes.

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Update in autoimmune and paraneoplastic myelopathies: Newly described antigen targets and antibody testing

Cited by 8 publications

References 65 publications

Neuromyelitis optica spectrum disorders associated with AQP4-positive-cancer—A case series

Neuromyelitis optica spectrum disorders associated with AQP4-positive-cancer—A case series

Clinical Approach to Myelopathy Diagnosis

Astrocytes as master modulators of neural networks: Synaptic functions and disease‐associated dysfunction of astrocytes

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