Adaptive Immunity Is the Key to the Understanding of Autoimmune and Paraneoplastic Inflammatory Central Nervous System Disorders

Weissert, Robert

doi:10.3389/fimmu.2017.00336

Cited by 27 publications

(19 citation statements)

References 158 publications

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“…B cells are a type of immune cell that can amplify the immune effect of T cells. B cells, being APCs, have the ability to present auto-antigens to CD4 + T-cells and promote Th1 and Th17 responses through their surface markers (Weissert, 2017). Some B cells undergo a proliferative phase and develop into plasma cells, which secrete myelin-specific antibodies.…”

Section: B Cellsmentioning

confidence: 99%

Inflammatory Role of TLR-MyD88 Signaling in Multiple Sclerosis

Chen

Chu

et al. 2020

Front. Mol. Neurosci.

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Multiple sclerosis (MS) is a neuro-autoimmune and neurodegenerative disorder leading to chronic inflammation, demyelination, axonal, and neuronal loss in the central nervous system (CNS). Despite intense research efforts, the pathogenesis of MS still remains unclear. Toll-like receptors (TLRs) are a family of type I transmembrane receptors that play a crucial role in the innate immune response. Myeloid differentiation factor 88 (MyD88) is the adaptor of major TLRs. It has been widely considered that the TLR-MyD88 signaling pathway plays an important role in the occurrence and development of autoimmune disease. Data have revealed that the TLR-MyD88 signaling may be involved in the pathogenesis of MS and experimental autoimmune encephalomyelitis (EAE), an animal model for MS, by regulating the antigen presentation of dendritic cells, the integrity of blood-brain barrier (BBB), and the activation of T cells and B cells. Here, we summarize the role of TLRs and MyD88 in MS and discuss the possible therapies that are based on these molecules.

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Section: B Cellsmentioning

confidence: 99%

Inflammatory Role of TLR-MyD88 Signaling in Multiple Sclerosis

Chen

Chu

et al. 2020

Front. Mol. Neurosci.

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“…But the underlying causes for the pathogenic pathways leading to the antibodies accessing the CNS and the associated immune response are, as yet, poorly understood. The role of T-cells has not yet been fully established in detail ( 3 , 4 ). Different mechanisms have been proposed, one including various infectious triggers which “prime” the immune system by activating T or/and B cells against similar epitopes by way of molecular mimicry, as in the case of Herpes simplex virus-encephalitis associated with NMDA-R-encephalitis ( 5 , 6 ).…”

Section: Introductionmentioning

confidence: 99%

Systematic Review: Syndromes, Early Diagnosis, and Treatment in Autoimmune Encephalitis

2018

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In recent years, new antibodies have been discovered which mediate autoimmune encephalitis. This immunological response can be triggered by an infection or a tumor. Classical onconeuronal antibodies are directed against intracellular neuronal agents but recently, a novel group of antibodies to neuronal cell-surface and synaptic antigens associated with different CNS-syndromes, has been discovered. Interestingly, the syndromes in this group can be successfully treated with immunotherapy and frequently do not have underlying tumors. The aim of this review is to describe the current state of knowledge about autoimmune encephalitis, in order to provide clinicians with a concise, up-to-date overview. Thus, a comprehensive literature search was performed in medical databases. The literature was carefully studied and new findings focusing on the symptoms, diagnosis and treatment were summarized and interpreted. Even though it might be challenging in some cases, the awareness of certain symptom constellations and demographic information, in combination with laboratory- and MRI-results, allows clinicians to make the diagnosis of probable autoimmune encephalitis at an early stage. Treatment can therefore be initiated faster, which significantly improves the outcome. Further investigations could define the underlying pathogenic mechanisms. Randomized controlled trials, paired with increasing clinical experience, will be necessary to improve the identification of affected patients, treatment strategies, and outcomes in the years to come.

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“… 1 – 3 In multiple sclerosis (MS), intrathecal immunoglobulin (Ig) production by clonally expanded and locally supported plasma cells remains a hallmark diagnostic finding, and ab depositions along with complement activation can be found in areas of active CNS demyelination. 4 Despite exhaustive investigations, no common autoantigen has been identified so far, 5 likely relating to the fact that MS is a heterogeneous disorder and may comprise several disease entities. 6 Based on the leading pathology of demyelination, possible autoantigens have been primarily projected into the myelin sheath and the oligodendrocyte.…”

Section: Introductionmentioning

confidence: 99%

Defining distinct features of anti-MOG antibody associated central nervous system demyelination

Weber

Derfuss

Metz

et al. 2018

Ther Adv Neurol Disord

137

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Extensive research over the last decades basically failed to identify a common cause of noninfectious inflammatory central nervous system (CNS) demyelinating disease. To a great extent, this may reflect that the group of inflammatory CNS demyelinating disorders likely contains multiple pathogenetically distinct disease entities. Indeed, the greatest success so far in deciphering the pathogenesis of a CNS demyelinating disorder resulted from the discovery of anti-aquaporin (AQP)-4 antibodies (ab), which allowed progressive delineation of neuromyelitis optica (NMO), formerly considered a variant of the most common CNS demyelinating disorder, multiple sclerosis (MS), as a distinct disease. Nowadays, AQP-4+ NMO is considered an autoimmune astrocytopathy, in which CNS demyelination occurs only as a consequence of a primary destruction of astrocytes. Delineating these patients concomitantly revealed that not all patients presenting with clinically NMO-suggestive disease phenotype express AQP-4 ab, which created the pathogenetically undefined category of NMO spectrum disorders (NMOSD). Recent investigations discovered that a subgroup of these AQP-4– NMOSD patients produce an ab response against myelin oligodendrocyte glycoprotein (MOG), a molecule expressed on the outer lamella of the myelin sheath. Using pathophysiologically meaningful cell-based assays, this humoral response is extremely rare in adult MS and absent in classical AQP-4+ NMO, sharply differentiating the evolving group from both established disorders. In this review, we summarize available clinical, immunological and histopathological data on patients with MOG+ CNS demyelinating disease. By comparing this clearly distinct cohort to AQP-4+ NMO as well as MS, we propose that MOG+ CNS demyelinating disease represents a distinct novel disease entity. In addition to its diagnostic value, we furthermore provide mechanistic insight on how this peripheral anti-MOG ab response may be of pathogenetic relevance in triggering acute flares of inflammatory CNS demyelination.

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Adaptive Immunity Is the Key to the Understanding of Autoimmune and Paraneoplastic Inflammatory Central Nervous System Disorders

Cited by 27 publications

References 158 publications

Inflammatory Role of TLR-MyD88 Signaling in Multiple Sclerosis

Inflammatory Role of TLR-MyD88 Signaling in Multiple Sclerosis

Systematic Review: Syndromes, Early Diagnosis, and Treatment in Autoimmune Encephalitis

Defining distinct features of anti-MOG antibody associated central nervous system demyelination

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