scholarly journals Myelin oligodendrocyte glycoprotein antibody-associated disease: an immunopathological study

Brain ◽  
2020 ◽  
Vol 143 (5) ◽  
pp. 1431-1446 ◽  
Author(s):  
Yoshiki Takai ◽  
Tatsuro Misu ◽  
Kimihiko Kaneko ◽  
Norio Chihara ◽  
Koichi Narikawa ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Humoral Immunity ◽  
Demyelinating Disease ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Demyelinating Diseases ◽  
Perivascular Spaces ◽  
Clinical Diagnoses ◽  
Demyelinating Lesions ◽  
Oligoclonal Igg ◽  
Aqp4 Antibody

Abstract Conformation-sensitive antibodies against myelin oligodendrocyte glycoprotein (MOG) are detectable in patients with optic neuritis, myelitis, opticomyelitis, acute or multiphasic disseminated encephalomyelitis (ADEM/MDEM) and brainstem/cerebral cortical encephalitis, but are rarely detected in patients with prototypic multiple sclerosis. So far, there has been no systematic study on the pathological relationship between demyelinating lesions and cellular/humoral immunity in MOG antibody-associated disease. Furthermore, it is unclear whether the pathomechanisms of MOG antibody-mediated demyelination are similar to the demyelination patterns of multiple sclerosis, neuromyelitis optica spectrum disorders (NMOSD) with AQP4 antibody, or ADEM. In this study, we immunohistochemically analysed biopsied brain tissues from 11 patients with MOG antibody-associated disease and other inflammatory demyelinating diseases. Patient median onset age was 29 years (range 9–64), and the median interval from attack to biopsy was 1 month (range 0.5–96). The clinical diagnoses were ADEM (n = 2), MDEM (n = 1), multiple brain lesions without encephalopathy (n = 3), leukoencephalopathy (n = 3) and cortical encephalitis (n = 2). All these cases had multiple/extensive lesions on MRI and were oligoclonal IgG band-negative. Most demyelinating lesions in 10 of 11 cases showed a perivenous demyelinating pattern previously reported in ADEM (153/167 lesions) and a fusion pattern (11/167 lesions) mainly in the cortico-medullary junctions and white matter, and only three lesions in two cases showed confluent demyelinated plaques. In addition, 60 of 167 demyelinating lesions (mainly in the early phase) showed MOG-dominant myelin loss, but relatively preserved oligodendrocytes, which were distinct from those of AQP4 antibody-positive NMOSD exhibiting myelin-associated glycoprotein-dominant oligodendrogliopathy. In MOG antibody-associated diseases, MOG-laden macrophages were found in the perivascular spaces and demyelinating lesions, and infiltrated cells were abundant surrounding multiple blood vessels in and around the demyelinating lesions, mainly consisting of macrophages (CD68; 1814 ± 1188 cells/mm2), B cells (CD20; 468 ± 817 cells/mm2), and T cells (CD3; 2286 ± 1951 cells/mm2), with CD4-dominance (CD4+ versus CD8+; 1281 ± 1196 cells/mm2 versus 851 ± 762 cells/mm2, P < 0.01). Humoral immunity, evidenced by perivascular deposits of activated complements and immunoglobulins, was occasionally observed in some MOG antibody-associated demyelinating lesions, and the frequency was much lower than that in AQP4 antibody-positive NMOSD. Subpial lesions with perivenous demyelination were observed in both ADEM and cortical encephalitis. Our study suggests that ADEM-like perivenous inflammatory demyelination with MOG-dominant myelin loss is a characteristic finding of MOG antibody-associated disease regardless of whether the diagnostic criteria of ADEM are met. These pathological features are clearly different from those of multiple sclerosis and AQP4 antibody-positive NMOSD, suggesting an independent autoimmune demyelinating disease entity.

scholarly journals Anti-Myelin Oligodendrocyte Glycoprotein and Human Leukocyte Antigens as Markers in Pediatric and Adolescent Multiple Sclerosis: on Diagnosis, Clinical Phenotypes, and Therapeutic Responses

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Maria P. Gontika ◽  
Maria C. Anagnostouli
Keyword(s):  
Multiple Sclerosis ◽  
Early Onset ◽  
Demyelinating Disease ◽  
Age Of Onset ◽  
Genetic Locus ◽  
Human Leukocyte ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Demyelinating Diseases ◽  
Disease Course ◽  
Clinical Phenotypes

Early-onset (pediatric and adolescent) multiple sclerosis (MS) is a well-established demyelinating disease that accounts for approximately 3-5% of all MS cases. Thus, identifying potential biomarkers that can reflect the pathogenic mechanisms, disease course and prognosis, and therapeutic response in such patients is of paramount importance. Myelin oligodendrocyte glycoprotein (MOG) has been regarded as a putative autoantigen and autoantibody target in patients with demyelinating diseases for almost three decades. However, recent studies have suggested that antibodies against MOG represent a distinct clinical entity of dominantly humoral profile, with a range of clinical phenotypes closely related to the age of onset, specific patterns of disease course, and responses to treatment. Furthermore, the major histocompatibility complex (MHC)—which has been regarded as the “gold standard” for attributing genetic burden in adult MS since the early 1970s—has also emerged as the primary genetic locus in early-onset MS, particularly with regard to the human leukocyte antigen (HLA) alleles DRB1⁎1501 and DRB1⁎0401. Recent studies have investigated the potential interactions among HLA, MOG, and environmental factors, demonstrating that early-onset MS is characterized by genetic, immunogenetic, immunological, and familial trait correlations. In this paper, we review recent evidence regarding HLA-genotyping and MOG antibodies—the two most important candidate biomarkers for early-onset MS—as well as their potential application in the diagnosis and treatment of MS.

Diagnosis of Multiple Sclerosis

2021 ◽  
pp. 540-547
Author(s):  
W. Oliver Tobin
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Demyelinating Disease ◽  
Acute Disseminated Encephalomyelitis ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Spectrum Disorder ◽  
Demyelinating Diseases ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
The Central Nervous System

Multiple sclerosis is the most common idiopathic inflammatory demyelinating disease of the central nervous system (CNS), with a prevalence of 1 in 500 to 1 in 2,000 people, depending on geography and various other factors. Idiopathic inflammatory demyelinating diseases are a group of related disorders that include acute disseminated encephalomyelitis, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein–immunoglobulin G–associated CNS demyelinating disease.

scholarly journals Theiler's Virus Infection: a Model for Multiple Sclerosis

2004 ◽  
Vol 17 (1) ◽  
pp. 174-207 ◽  
Author(s):  
Emilia L. Oleszak ◽  
J. Robert Chang ◽  
Herman Friedman ◽  
Christos D. Katsetos ◽  
Chris D. Platsoucas
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Molecular Mimicry ◽  
Experimental Models ◽  
Demyelinating Diseases ◽  
Acute Disease ◽  
Theiler's Virus ◽  
Spinal Cord Atrophy ◽  
Demyelinating Lesions ◽  
Mononuclear Cell Infiltrates

SUMMARY Both genetic background and environmental factors, very probably viruses, appear to play a role in the etiology of multiple sclerosis (MS). Lessons from viral experimental models suggest that many different viruses may trigger inflammatory demyelinating diseases resembling MS. Theiler's virus, a picornavirus, induces in susceptible strains of mice early acute disease resembling encephalomyelitis followed by late chronic demyelinating disease, which is one of the best, if not the best, animal model for MS. During early acute disease the virus replicates in gray matter of the central nervous system but is eliminated to very low titers 2 weeks postinfection. Late chronic demyelinating disease becomes clinically apparent approximately 2 weeks later and is characterized by extensive demyelinating lesions and mononuclear cell infiltrates, progressive spinal cord atrophy, and axonal loss. Myelin damage is immunologically mediated, but it is not clear whether it is due to molecular mimicry or epitope spreading. Cytokines, nitric oxide/reactive nitrogen species, and costimulatory molecules are involved in the pathogenesis of both diseases. Close similarities between Theiler's virus-induced demyelinating disease in mice and MS in humans, include the following: major histocompatibility complex-dependent susceptibility; substantial similarities in neuropathology, including axonal damage and remyelination; and paucity of T-cell apoptosis in demyelinating disease. Both diseases are immunologically mediated. These common features emphasize the close similarities of Theiler's virus-induced demyelinating disease in mice and MS in humans.

scholarly journals Multiple Sclerosis in Malaysia: Demographics, Clinical Features, and Neuroimaging Characteristics

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
S. Viswanathan ◽  
N. Rose ◽  
A. Masita ◽  
J. S. Dhaliwal ◽  
S. D. Puvanarajah ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Demyelinating Disease ◽  
Age At Onset ◽  
Positive Family History ◽  
Disease Onset ◽  
Demyelinating Diseases ◽  
Lesion Length ◽  
Relapsing Remitting ◽  
Spectrum Disorders

Background. Multiple sclerosis (MS) is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country.Objectives. To investigate the spectrum of multiple sclerosis in Malaysia.Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia.Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald’s criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders.Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here.

Recent advances on immunosuppressive drugs and remyelination enhancers for the treatment of multiple sclerosis

2021 ◽  
Vol 27 ◽  
Author(s):  
Jennifer Cadenas-Fernández ◽  
Pablo Ahumada-Pascual ◽  
Luis Sanz Andreu ◽  
Ana Velasco
Keyword(s):  
Multiple Sclerosis ◽  
Intracellular Signaling ◽  
Demyelinating Disease ◽  
Lipid Synthesis ◽  
Immunosuppressive Drugs ◽  
Nerve Fibers ◽  
Myelin Sheaths ◽  
Demyelinating Lesions ◽  
The Central Nervous System ◽  
Lipid Structures

: Mammalian nervous systems depend crucially on myelin sheaths covering the axons. In the central nervous system, myelin sheaths consist of lipid structures which are generated from the membrane of oligodendrocytes (OL). These sheaths allow fast nerve transmission, protect axons and provide them metabolic support. In response to specific traumas or pathologies, these lipid structures can be destabilized and generate demyelinating lesions. Multiple sclerosis (MS) is an example of a demyelinating disease in which the myelin sheaths surrounding the nerve fibers of the brain and spinal cord are damaged. MS is the leading cause of neurological disability in young adults in many countries, and its incidence has been increasing in recent decades. Related to its etiology, it is known that MS is an autoimmune and inflammatory CNS disease. However, there are no effective treatments for this disease and the immunomodulatory therapies that currently exist have proven limited success since they only delay the progress of the disease. Nowadays, one of the main goals in the MS research is to find treatments which allows the recovery of neurological disabilities due to demyelination. To this end, different approaches, such as modulating intracellular signaling or regulating the lipid metabolism of OLs, are being considered. Here, in addition to immunosuppressive or immunomodulatory drugs that reduce the immune response against myelin sheaths, we review a diverse group of drugs that promotes endogenous remyelination in MS patients and whose use may be interesting as potential therapeutic agents in MS disease. To this end, we compile specific treatments against MS that are currently in the market with remyelination strategies which have entered into human clinical trials for future reparative MS therapies. The method used in this study is a systematic literature review on PubMed, Web of Science and Science Direct databases up to May 31, 2020. To narrow down the search results in databases, more specific keywords, such as, “myelin sheath”, “remyelination”, “demyelination”, “oligodendrocyte” and “lipid synthesis” were used to focus the search. We favoured papers published after January, 2015, but did not exclude earlier seminal papers.

Еarly diagnosis of multiple sclerosis: experience with the use of class G oligoclonal immunoglobulin

2021 ◽  
Vol 26 (3) ◽  
pp. 34-39
Author(s):  
Z. A. Goncharova ◽  
Y. Y. Pogrebnova ◽  
N. M. Yarosh ◽  
S. M.M. Sehweil
Keyword(s):  
Multiple Sclerosis ◽  
Early Diagnosis ◽  
Literature Review ◽  
Demyelinating Disease ◽  
Mcdonald Criteria ◽  
Mri Features ◽  
Oligoclonal Igg ◽  
Relationship Of ◽  
The Relationship

The article presents the literature review and our experience in early diagnosis of multiple sclerosis based on the updated McDonald criteria of 2017. The study included 256 patients with clinic symptoms of probable idiopathic infl ammatory demyelinating disease, including rare and atypical forms of demyelination. As a result of the study the sensitivity and specifi city of the determination of oligoclonal immunoglobulin G in the population of Rostov-on-Don was described for the fi rst time, including dependence of the duration of the disease. The relationship of clinical and MRI features of the fi rst attack of the disease with the probability of determining oligoclonal IgG in the cerebrospinal fl uid is refl ected

Multiple sclerosis and other demyelinating diseases

2011 ◽  
Author(s):  
Alastair Compston
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Past History ◽  
Central Pontine Myelinolysis ◽  
Clinical Manifestations ◽  
Nerve Impulse ◽  
Demyelinating Diseases ◽  
Clinical Neurology ◽  
Disease Heterogeneity ◽  
Axonal Dysfunction

The oligodendrocyte–myelin unit subserves saltatory conduction of the nerve impulse in the healthy central nervous system. At one time, many disease processes were thought exclusively to target the structure and function of myelin. Therefore, they were designated ‘demyelinating diseases’. But recent analyses, based mainly on pathological and imaging studies, (re)emphasize that axons are also directly involved in these disorders during both the acute and chronic phases. Another ambiguity is the extent to which these are inflammatory conditions. Here, distinctions should be made between inflammation, as a generic process, and autoimmunity in which rather a specific set of aetiological and mechanistic conditions pertain. And there are differences between disorders that are driven primarily by immune processes and those in which inflammation occurs in response to pre-existing tissue damage.With these provisos, the pathological processes of demyelination and associated axonal dysfunction often account for episodic neurological symptoms and signs referable to white matter tracts of the brain, optic nerves, or spinal cord when these occur in young people. This is the clinical context in which the possibility of ‘demyelinating disease’ is usually considered by physicians and, increasingly, the informed patient. Neurologists will, with appropriate cautions, also be prepared to diagnose demyelinating disease in older patients presenting with progressive symptoms implicating these same pathways even when there is no suggestive past history. Both in its typical and atypical forms multiple sclerosis remains by far the commonest demyelinating disease. But acute disseminated encephalomyelitis, the leucodystrophies, and central pontine myelinolysis also need to be considered in particular circumstances; and multiple sclerosis itself has a differential diagnosis in which the relapsing-remitting course is mimicked by conditions not associated with direct injury to the axon–glial unit. Since our understanding of the cause, pathogenesis and features of demyelinating disease remains incomplete, classification combines aspects of the aetiology, clinical features, pathology, and laboratory components. Whether the designation ‘multiple sclerosis’ encapsulates one or more conditions is now much debated. We anticipate that a major part of future studies in demyelinating disease will be further to resolve this question of disease heterogeneity leading to a new taxonomy based on mechanisms rather than clinical empiricism. But, for now, the variable ages of onset, unpredictable clinical course, protean clinical manifestations, and non-specific laboratory investigations continue to make demyelinating disease one of the more challenging diagnostic areas in clinical neurology.

scholarly journals Myelin oligodendrocyte glycoprotein antibodies in pathologically proven multiple sclerosis: frequency, stability and clinicopathologic correlations

2007 ◽  
Vol 13 (1) ◽  
pp. 7-16 ◽  
Author(s):  
S J Pittock ◽  
M Reindl ◽  
S Achenbach ◽  
T Berger ◽  
W Bruck ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Western Blot ◽  
Demyelinating Disease ◽  
Clinical Course ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Poor Agreement ◽  
Predictive Role ◽  
Mog Antibodies ◽  
Serial Measurements

Controversy exists regarding the pathogenic or predictive role of anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in patients with multiple sclerosis (MS). Four immunopathological patterns (IP) have been recognized in early active MS lesions, suggesting heterogeneous pathogenic mechanisms. Whether MOG antibodies contribute to this pathological heterogeneity and potentially serve as biomarkers to identify specific pathological patterns is unknown. Here we report the frequencies of antibodies to human recombinant MOG (identified by Western blot and enzymelinked immunoabsorbent assay (ELISA)) in patients with pathologically proven demyelinating disease, and investigate whether antibody status is associated with clinical course, HLA-DR2 genotype, IP or treatment response to plasmapheresis. The biopsy cohort consisted of 72 patients: 12 pattern I, 43 pattern II and 17 pattern III. No association was found between MOG antibody status and conversion to clinically definite MS, DR-2 status, IP or response to plasmapheresis. There was poor agreement between Western blot and ELISA (kappa=0.07 for MOG IgM). Fluctuations in antibody seropositivity were seen for 3/4 patients tested serially by Western blot. This study does not support a pathologic pattern-specific role for MOG-antibodies. Variable MOG-antibody status on serial measurements, coupled with the lack of Western blot and ELISA correlations, raises concern regarding the use of MOG-antibody as an MS biomarker and underscores the need for methodological consensus.

scholarly journals Hypoperfusion of the Cerebral White Matter in Multiple Sclerosis: Possible Mechanisms and Pathophysiological Significance

2008 ◽  
Vol 28 (10) ◽  
pp. 1645-1651 ◽  
Author(s):  
Jacques De Keyser ◽  
Christel Steen ◽  
Jop P Mostert ◽  
Marcus W Koch
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Adrenergic Receptors ◽  
Perfusion Magnetic Resonance Imaging ◽  
Cerebral White Matter ◽  
Perivascular Spaces ◽  
Axonal Loss ◽  
Normal Appearing White Matter ◽  
Demyelinating Lesions ◽  
The Central Nervous System

Multiple sclerosis (MS) is a disease of the central nervous system characterized by patchy areas of demyelination, inflammation, axonal loss and gliosis, and a diffuse axonal degeneration throughout the so-called normal-appearing white matter (NAWM). A number of recent studies using perfusion magnetic resonance imaging in both relapsing and progressive forms of MS have shown a decreased perfusion of the NAWM, which does not appear to be secondary to axonal loss. The reduced perfusion of the NAWM in MS might be caused by a widespread astrocyte dysfunction, possibly related to a deficiency in astrocytic β2-adrenergic receptors and a reduced formation of cAMP, resulting in a reduced uptake of K+ at the nodes of Ranvier and a reduced release of K+ in the perivascular spaces. Pathologic and imaging studies suggest that ischemic changes might be involved in the development of a subtype of focal demyelinating lesions (type III lesions), and there appears to exist a relationship between decreased white matter perfusion and cognitive dysfunction in patients with MS.

Aquaporin-4 autoimmune syndrome and anti-aquaporin-4 antibody-negative opticospinal multiple sclerosis in Japanese

2009 ◽  
Vol 15 (7) ◽  
pp. 834-847 ◽  
Author(s):  
T Matsushita ◽  
N Isobe ◽  
T Matsuoka ◽  
N Shi ◽  
Y Kawano ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Serum Antibody ◽  
Demyelinating Diseases ◽  
Aquaporin 4 ◽  
Immunological Parameters ◽  
Antibody Positivity ◽  
Antibody Titers ◽  
Ifn Γ ◽  
Aqp4 Antibody

Background Antibodies to aquaporin-4 (AQP4) are found in a fraction of Japanese opticospinal multiple sclerosis (OSMS) patients. However, it remains unknown whether anti-AQP4 antibody-positive and negative OSMS patients possess an identical disease. Objective The objective of the current study was to clarify immunological differences between the two groups of patients. Methods We studied the serum antibody titers against AQP4 in 191 patients with idiopathic central nervous system demyelinating diseases and clarified their relationships with immunological parameters. Results Anti-AQP4 antibody positivity rate was higher in patients with OSMS (21/58, 36.2%), idiopathic recurrent myelitis (4/17, 23.5%), and recurrent optic neuritis (7/26, 26.9%), than in conventional MS (CMS) patients (6/90, 6.7%) and patients with other diseases (0/87). Anti-AQP4 antibody titer was significantly higher in patients with SS-A/B antibodies than in those without them. Anti-AQP4 antibody-negative OSMS patients showed significantly higher CD4+IFN-γ+IL-4−T cell percentages and intracellular IFN-γ/IL-4 ratios than anti-AQP4 antibody-positive patients, anti-AQP4 antibody-negative CMS patients, and healthy controls, and CD4+IFN-γ+IL-4−T cell percentages were negatively correlated with anti-AQP4 antibody titers. Conclusion Anti-AQP4 antibody-positive patients are immunologically distinct from anti-AQP4 antibody-negative OSMS patients owing to a Th2 shift in the former group in comparison to a Th1 shift in the latter.

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