43 results on '"Reindl, Markus"'
Search Results
2. Blood parameters in pediatric myelin oligodendrocyte glycoprotein antibody-associated disorders.
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Peternell, Alina, Lechner, Christian, Breu, Markus, Preisel, Martin, Schimmel, Mareike, Eisenkölbl, Astrid, Zobel, Joachim, Wendel, Eva-Maria, Reindl, Markus, Rostásy, Kevin, and Baumann, Matthias
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MYELIN oligodendrocyte glycoprotein ,NEUROMYELITIS optica ,LEUKOCYTE count ,POSTVACCINAL encephalitis ,PLATELET lymphocyte ratio - Abstract
Patients with myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) clinically present e.g. with acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), transverse myelitis (TM) or aquaporin-4-IgG (AQP4-IgG) negative neuromyelitis optica spectrum disorders (NMOSD)-like phenotypes. We aimed to analyze and compare blood parameters in children with MOGAD, AQP4-IgG-positive NMOSD (hence NMOSD), multiple sclerosis (MS) and healthy controls (HC). We evaluated differences in complete blood counts (CBC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and C-reactive protein (CRP) between these four groups and within the groups between clinical attack, acute treatment and remission. Our cohort consisted of 174 children and adolescents with a total of 550 timepoints: 66 patients had MOGAD (202 timepoints), 11 NMOSD (76 timepoints), 58 MS (219 timepoints) and 39 were HC (53 timepoints). At clinical attack, leukocyte counts were elevated in MOGAD compared to remission (p < 0.001) and compared to all other groups (p < 0.001). NLR was high in MOGAD and NMOSD, and PLR was high in NMOSD, however, after correction for multiple testing these findings did not remain significant. While glucocorticoids caused an increase of leukocyte counts and NLR in NMOSD and MS, these values remained stable during acute treatment in MOGAD. In remission, NLR normalized in MOGAD, while it stayed high in NMOSD. PLR increased in NMOSD and was significantly higher compared to all other groups. Some blood parameters, mainly leukocyte and differential counts, might help clinicians to evaluate disease activity, differentiate relapses from pseudo-relapses and even distinguish between different disease entities. • Leukocyte and differential counts show differences between pediatric patients with MOGAD, AQP4-ab positive NMOSD and MS. • Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio differ between the groups and between acute attack/remission. • These parameters might help clinicians to evaluate disease activity and even distinguish between different disease entities. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Cell-based assays for the detection of MOG antibodies: a comparative study
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Gastaldi, Matteo, Scaranzin, Silvia, Jarius, Sven, Wildeman, Brigitte, Zardini, Elisabetta, Mallucci, Giulia, Rigoni, Eleonora, Vegezzi, Elisa, Foiadelli, Thomas, Savasta, Salvatore, Banfi, Paola, Versino, Maurizio, Benedetti, Luana, Novi, Giovanni, Mancardi, Margherita Maria, Giacomini, Thea, Annovazzi, Pietro, Baroncini, Damiano, Ferraro, Diana, Lampasona, Vito, Reindl, Markus, Waters, Patrick, and Franciotta, Diego
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- 2020
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4. Basic CSF parameters and MRZ reaction help in differentiating MOG antibody-associated autoimmune disease versus multiple sclerosis.
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Vlad, Benjamin, Reichen, Ina, Neidhart, Stephan, Hilty, Marc, Lekaditi, Dimitra, Heuer, Christine, Eisele, Amanda, Ziegler, Mario, Reindl, Markus, Lutterotti, Andreas, Regeniter, Axel, and Jelcic, Ilijas
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MYELIN sheath diseases ,MULTIPLE sclerosis ,MYELIN oligodendrocyte glycoprotein ,AUTOIMMUNE diseases ,CENTRAL nervous system diseases ,DEMYELINATION - Abstract
Background: Myelin oligodendrocyte glycoprotein antibody-associated autoimmune disease (MOGAD) is a rare monophasic or relapsing inflammatory demyelinating disease of the central nervous system (CNS) and can mimic multiple sclerosis (MS). The variable availability of live cell-based MOG-antibody assays and difficulties in interpreting low-positive antibody titers can complicate diagnosis. Literature on cerebrospinal fluid (CSF) profiles in MOGAD versus MS, one of the most common differential diagnoses, is scarce. We here analyzed the value of basic CSF parameters to i) distinguish different clinical MOGAD manifestations and ii) differentiate MOGAD from MS. Methods: This is retrospective, single-center analysis of clinical and laboratory data of 30 adult MOGAD patients and 189 adult patients with relapsing-remitting multiple sclerosis. Basic CSF parameters included CSF white cell count (WCC) and differentiation, CSF/serum albumin ratio (Q
Alb ), intrathecal production of immunoglobulins, CSF-restricted oligoclonal bands (OCB) and MRZ reaction, defined as intrathecal production of IgG reactive against at least 2 of the 3 viruses measles (M), rubella (R) and varicella zoster virus (Z). Results: MOGAD patients with myelitis were more likely to have a pleocytosis, a QAlb elevation and a higher WCC than those with optic neuritis, and, after review and combined analysis of our and published cases, they also showed a higher frequency of intrathecal IgM synthesis. Compared to MS, MOGAD patients had significantly more frequently neutrophils in CSF and WCC>30/µl, QAlb >10x10-3 , as well as higher mean QAlb values, but significantly less frequently CSF plasma cells and CSF-restricted OCB. A positive MRZ reaction was present in 35.4% of MS patients but absent in all MOGAD patients. Despite these associations, the only CSF parameters with relevant positive likelihood ratios (PLR) indicating MOGAD were QAlb >10x10-3 (PLR 12.60) and absence of CSF-restricted OCB (PLR 14.32), whereas the only relevant negative likelihood ratio (NLR) was absence of positive MRZ reaction (NLR 0.00). Conclusion: Basic CSF parameters vary considerably in different clinical phenotypes of MOGAD, but QAlb >10x10-3 and absence of CSF-restricted OCB are highly useful to differentiate MOGAD from MS. A positive MRZ reaction is confirmed as the strongest CSF rule-out parameter in MOGAD and could be useful to complement the recently proposed diagnostic criteria. [ABSTRACT FROM AUTHOR]- Published
- 2023
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5. Immunohistochemistry
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Höftberger, Romana, Mader, Simone, Reindl, Markus, Deisenhammer, Florian, editor, Sellebjerg, Finn, editor, Teunissen, Charlotte E, editor, and Tumani, Hayrettin, editor
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- 2015
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6. MRI of the first event in pediatric acquired demyelinating syndromes with antibodies to myelin oligodendrocyte glycoprotein
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Baumann, Matthias, Grams, Astrid, Djurdjevic, Tanja, Wendel, Eva-Maria, Lechner, Christian, Behring, Bettina, Blaschek, Astrid, Diepold, Katharina, Eisenkölbl, Astrid, Fluss, Joel, Karenfort, Michael, Koch, Johannes, Konuşkan, Bahadir, Leiz, Steffen, Merkenschlager, Andreas, Pohl, Daniela, Schimmel, Mareike, Thiels, Charlotte, Kornek, Barbara, Schanda, Kathrin, Reindl, Markus, and Rostásy, Kevin
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- 2018
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7. Humoral signatures of MOG-antibody-associated disease track with age and disease activity
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Spatola, Marianna, Chuquisana, Omar, Jung, Wonyeong, Lopez, Joseph A., Wendel, Eva-Maria, Ramanathan, Sudarshini, Keller, Christian W., Hahn, Tim, Meinl, Edgar, Reindl, Markus, Dale, Russell C., Wiendl, Heinz, Lauffenburger, Douglas A., Rostásy, Kevin, Brilot, Fabienne, Alter, Galit, Lünemann, Jan, and Universitäts- und Landesbibliothek Münster
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humoral signatures ,myelin oligodendrocyte glycoprotein ,MOGAD ,antibody ,Fc gamma receptors ,demyelination ,610 Medicine and health ,Medicine and health ,ddc:610 ,General Biochemistry, Genetics and Molecular Biology - Abstract
Myelin oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated disease (MOGAD) is an inflammatory demyelinating disease of the CNS. Although MOG is encephalitogenic in different mammalian species, the mechanisms by which human MOG-specific Abs contribute to MOGAD are poorly understood. Here, we use a systems-level approach combined with high-dimensional characterization of Ab-associated immune features to deeply profile humoral immune responses in 123 patients with MOGAD. We show that age is a major determinant for MOG-antibody-related immune signatures. Unsupervised clustering additionally identifies two dominant immunological endophenotypes of MOGAD. The pro-inflammatory endophenotype characterized by increased binding affinities for activating Fcγ receptors (FcγRs), capacity to activate innate immune cells, and decreased frequencies of galactosylated and sialylated immunoglobulin G (IgG) glycovariants is associated with clinically active disease. Our data support the concept that FcγR-mediated effector functions control the pathogenicity of MOG-specific IgG and suggest that FcγR-targeting therapies should be explored for their therapeutic potential in MOGAD., Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster).
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- 2023
8. Serum neurofilament light-chain levels in children with monophasic myelin oligodendrocyte glycoprotein-associated disease, multiple sclerosis, and other acquired demyelinating syndrome.
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Wendel, Eva-Maria, Bertolini, Annikki, Kousoulos, Lampros, Rauchenzauner, Markus, Schanda, Kathrin, Wegener-Panzer, Andreas, Baumann, Matthias, Reindl, Markus, Otto, Markus, and Rostásy, Kevin
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DEMYELINATION ,MULTIPLE sclerosis ,POSTVACCINAL encephalitis ,MYELIN oligodendrocyte glycoprotein ,CYTOPLASMIC filaments ,MYELITIS ,MONOCLONAL gammopathies - Abstract
Objective: To assess the diagnostic and prognostic potential of serum neurofilament light chain (sNfL) in children with first acquired demyelinating syndrome (ADS). Methods: We selected 129 children with first ADS including 19 children with myelin oligodendrocyte glycoprotein (MOG)-antibody associated disease (MOGAD), 36 MOG/AQP4-seronegative ADS, and 74 with multiple sclerosis (MS) from the BIOMARKER study cohort. All children had a complete set of clinical, radiological, laboratory data and serum for NfL measurement using a highly sensitive digital ELISA (SIMOA). A control group of 35 children with non-inflammatory neurological diseases was included. sNfL levels were compared across patient groups according to clinical, laboratory, neuroradiological features and outcome after 2 years. Results: sNfL levels were significantly increased in MOGAD, seronegative ADS and MS compared to controls (p -value < 0.001), in particular in children with an acute disseminated encephalomyelitis (ADEM)-like magnetic resonance imaging (MRI) pattern (p < 0.001) or longitudinally extensive myelitis (p < 0.01). In pediatric MS, elevated sNfL levels were significantly associated with higher numbers of cerebral (p < 0.001) and presence of spinal (p < 0.05) MRI lesions at baseline and predicted a higher number of relapses (p < 0.05). Conclusion: sNfL levels are significantly elevated in all three studied pediatric ADS subtypes indicating neuroaxonal injury. In pediatric MS high levels of sNfL are associated with risk factors for disease progression. [ABSTRACT FROM AUTHOR]
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- 2022
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9. Complement Activation Is a Prominent Feature of MOGAD.
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Keller, Christian W., Lopez, Joseph A., Wendel, Eva‐Maria, Ramanathan, Sudarshini, Gross, Catharina C., Klotz, Luisa, Reindl, Markus, Dale, Russell C., Wiendl, Heinz, Rostásy, Kevin, Brilot, Fabienne, and Lünemann, Jan D.
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NEUROMYELITIS optica ,COMPLEMENT activation ,MYELIN oligodendrocyte glycoprotein ,CHILD patients ,ADULTS ,COMPLEMENT inhibition - Abstract
Myelin oligodendrocyte glycoprotein (MOG)‐antibody (Ab)–associated diseases (MOGADs) account for a substantial proportion of pediatric and adult patients who present with acquired demyelinating disorders. Its pathogenesis and optimal therapy are incompletely understood. We profiled systemic complement activation in adult and pediatric patients with MOGAD compared with patients with relapse‐onset multiple sclerosis, patients with neuromyelitis optica spectrum disorder, and pediatric control and adult healthy donors. Proteins indicative of systemic classical and alternative complement activation were substantially increased in patients with MOGAD compared to control groups. Elevated levels were detected in both adult and pediatric cases and across all clinical syndromes. Complement inhibition should be explored for its therapeutic merit in patients with MOGAD. ANN NEUROL 2021;90:976–982 [ABSTRACT FROM AUTHOR]
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- 2021
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10. Human antibodies against the myelin oligodendrocyte glycoprotein can cause complement-dependent demyelination
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Peschl, Patrick, Schanda, Kathrin, Zeka, Bleranda, Given, Katherine, Böhm, Denise, Ruprecht, Klemens, Saiz, Albert, Lutterotti, Andreas, Rostásy, Kevin, Höftberger, Romana, Berger, Thomas, Macklin, Wendy, Lassmann, Hans, Bradl, Monika, Bennett, Jeffrey L, Reindl, Markus, University of Zurich, and Reindl, Markus
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Adult ,Male ,Adolescent ,2804 Cellular and Molecular Neuroscience ,610 Medicine & health ,Mice, Transgenic ,lcsh:RC346-429 ,Antibodies ,Mice ,Young Adult ,Organ Culture Techniques ,immune system diseases ,Cerebellum ,Animals ,Humans ,MOG ,Child ,lcsh:Neurology. Diseases of the nervous system ,Aged ,Organotypic slice culture ,2403 Immunology ,EAE ,Research ,Neuromyelitis Optica ,2800 General Neuroscience ,Infant ,hemic and immune systems ,Complement System Proteins ,Middle Aged ,10040 Clinic for Neurology ,nervous system diseases ,Rats ,HEK293 Cells ,nervous system ,Myelin oligodendrocyte glycoprotein ,Rats, Inbred Lew ,2808 Neurology ,Child, Preschool ,Neuromyelitis optica spectrum disorders ,Female ,Myelin-Oligodendrocyte Glycoprotein ,Demyelinating Diseases - Abstract
Background Antibodies to the myelin oligodendrocyte glycoprotein (MOG) are associated with a subset of inflammatory demyelinating diseases of the central nervous system such as acute disseminated encephalomyelitis and neuromyelitis optica spectrum disorders. However, whether human MOG antibodies are pathogenic or an epiphenomenon is still not completely clear. Although MOG is highly conserved within mammals, previous findings showed that not all human MOG antibodies bind to rodent MOG. We therefore hypothesized that human MOG antibody-mediated pathology in animal models may only be evident using species-specific MOG antibodies. Methods We screened 80 human MOG antibody-positive samples for their reactivity to mouse and rat MOG using either a live cell-based assay or immunohistochemistry on murine, rat, and human brain tissue. Selected samples reactive to either human MOG or rodent MOG were subsequently tested for their ability to induce complement-mediated damage in murine organotypic brain slices or enhance demyelination in an experimental autoimmune encephalitis (EAE) model in Lewis rats. The MOG monoclonal antibody 8-18-C5 was used as a positive control. Results Overall, we found that only a subset of human MOG antibodies are reactive to mouse (48/80, 60%) or rat (14/80, 18%) MOG. Purified serum antibodies from 10 human MOG antibody-positive patients (8/10 reactive to mouse MOG, 6/10 reactive to rat MOG), 3 human MOG-negative patients, and 3 healthy controls were tested on murine organotypic brain slices. Purified IgG from one patient with high titers of anti-human, mouse, and rat MOG antibodies and robust binding to myelin tissue produced significant, complement-mediated myelin loss in organotypic brain slices, but not in the EAE model. Monoclonal 8-18-C5 MOG antibody caused complement-mediated demyelination in both the organotypic brain slice model and in EAE. Conclusion This study shows that a subset of human MOG antibodies can induce complement-dependent pathogenic effects in a murine ex vivo animal model. Moreover, a high titer of species-specific MOG antibodies may be critical for demyelinating effects in mouse and rat animal models. Therefore, both the reactivity and titer of human MOG antibodies must be considered for future pathogenicity studies. Electronic supplementary material The online version of this article (10.1186/s12974-017-0984-5) contains supplementary material, which is available to authorized users.
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- 2017
11. Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease and Varicella Zoster Virus Infection - Frequency of an Association.
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Di Pauli, Franziska, Morschewsky, Paul, Berek, Klaus, Auer, Michael, Bauer, Angelika, Berger, Thomas, Bsteh, Gabriel, Rhomberg, Paul, Schanda, Kathrin, Zinganell, Anne, Deisenhammer, Florian, Reindl, Markus, and Hegen, Harald
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MYELIN oligodendrocyte glycoprotein ,VARICELLA-zoster virus ,HERPES zoster ,VIRUS diseases ,NEUROMYELITIS optica ,TRANSVERSE myelitis - Abstract
To determine whether there is a correlation between myelin oligodendrocyte glycoprotein (MOG) antibody-associated diseases and varicella zoster virus (VZV) infection. We provide a case report and performed a study to determine the frequency of MOG antibodies (MOG-IgG) in neurological VZV infections. Patients admitted to the Medical University of Innsbruck from 2008–2020 with a diagnosis of a neurological manifestation of VZV infection (n=59) were included in this study; patients with neuroborreliosis (n=34) served as control group. MOG-IgG was detected using live cell-based assays. In addition, we performed a literature review focusing on MOG and aquaporin-4 (AQP4) antibodies and their association with VZV infection. Our case presented with VZV-associated longitudinally extensive transverse myelitis and had MOG-IgG at a titer of 1:1280. In the study, we did not detect MOG-IgG in any other patient neither in the VZV group (including 15 with VZV encephalitis/myelitis) nor in the neuroborreliosis group. In the review of the literature, 3 cases with MOG-IgG and additional 9 cases with AQP4 IgG associated disorders in association with a VZV infection were identified. MOG-IgG are rarely detected in patients with VZV infections associated with neurological diseases. [ABSTRACT FROM AUTHOR]
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- 2021
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12. Frequency of myelin oligodendrocyte glycoprotein antibodies in a large cohort of neurological patients.
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Held, Friederike, Kalluri, Sudhakar Reddy, Berthele, Achim, Klein, Ana-Katharina, Reindl, Markus, and Hemmer, Bernhard
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MYELIN oligodendrocyte glycoprotein ,NEUROMYELITIS optica ,IMMUNOGLOBULINS ,ADULTS ,IMMUNOGLOBULIN G - Abstract
Background: Myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOG-AD) is recognized as a distinct nosological entity. IgG antibodies against MOG (MOG-Ab) overlap with neuromyelitis optica spectrum disorders (NMOSD) phenotype in adults. However, an increasing number of clinical phenotypes have been reported to be associated with MOG-Ab. Objective: To investigate the seroprevalence of MOG-Ab under consideration of demographics, disease entities and time course in a large cohort of unselected neurological patients. Methods: Blood samples of 2.107 consecutive adult neurologic patients admitted to our department between 2016-2017 were tested for MOG-Ab using a cell-based assay. MOG-Ab persistence was analyzed in follow-up samples. External validation was performed in two independent laboratories. Results: We found MOG-Ab in 25 of 2.107 (1.2%) patients. High antibody ratios were mostly associated with NMOSD and MOG-AD phenotype (5/25). Low ratios occurred in a wide range of neurological diseases, predominantly in other demyelinating CNS diseases (5/25) and stroke (6/25). MOG-Ab persistence over time was not confined to NMOSD and MOG-AD phenotype. Conclusion: The present study demonstrates the occurrence of MOG-Ab in a wide range of neurological diseases. Only high MOG-Ab ratios were associated with a defined clinical phenotype, but low MOG-Ab ratios were not. The diagnostic value of low MOG-Ab is thus highly limited. [ABSTRACT FROM AUTHOR]
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- 2021
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13. Age-dependent favorable visual recovery despite significant retinal atrophy in pediatric MOGAD: how much retina do you really need to see well?
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Havla, Joachim, Pakeerathan, Thivya, Schwake, Carolin, Bennett, Jeffrey L., Kleiter, Ingo, Felipe-Rucián, Ana, Joachim, Stephanie C., Lotz-Havla, Amelie S., Kümpfel, Tania, Krumbholz, Markus, Wendel, Eva M., Reindl, Markus, Thiels, Charlotte, Lücke, Thomas, Hellwig, Kerstin, Gold, Ralf, Rostasy, Kevin, and Ayzenberg, Ilya
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MYELIN oligodendrocyte glycoprotein ,OPTICAL coherence tomography ,VISUAL evoked potentials ,ATROPHY ,OPTIC neuritis - Abstract
Background: To investigate age-related severity, patterns of retinal structural damage, and functional visual recovery in pediatric and adult cohorts of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) optic neuritis (ON).Methods: All MOGAD patients from the 5 participating centers were included. Patients with initial manifestation <18 years were included in the pediatric (MOGADped) cohort and patients with ≥18 years in the adult (MOGADadult) cohort. For patients with MOGAD ON, examinations at least ≥6 months after ON onset were included in the analyses. Using spectral domain optical coherence tomography (SD-OCT), we acquired peripapillary retinal nerve fiber layer thickness (pRNFL) and volumes of combined ganglion cell and inner plexiform layer (GCIPL). High- and 2.5% low-contrast visual acuity (HCVA, LCVA) and visual-evoked potentials (VEP) were obtained.Results: Twenty MOGADped (10.3±3.7 years, 30 MOGAD ON eyes) and 39 MOGADadult (34.9±11.6 years, 42 MOGAD ON eyes) patients were included. The average number of ON episodes per ON eye was similar in both groups (1.8±1.3 and 2.0±1.7). In both pediatric and adult MOGAD, ON led to pronounced neuroaxonal retinal atrophy (pRNFL: 63.1±18.7 and 64.3±22.9 μm; GCIPL: 0.42±0.09 and 0.44±0.13 mm3, respectively) and moderate delay of the VEP latencies (117.9±10.7 and 118.0±14.5 ms). In contrast, visual acuity was substantially better in children (HCVA: 51.4±9.3 vs. 35.0±20.6 raw letters, p=0.001; LCVA: 22.8±14.6 vs. 13.5±16.4, p=0.028). Complete visual recovery (HCVA-logMAR 0.0) occurred in 73.3% of MOGADped and 31% MOGADadults ON eyes, while 3.3% and 31% demonstrated moderate to severe (logMAR > 0.5) visual impairment. Independent of retinal atrophy, age at ON onset significantly correlated with visual outcome.Conclusion: Pediatric MOGAD ON showed better visual recovery than adult MOGAD ON despite profound and almost identical neuroaxonal retinal atrophy. Age-related cortical neuroplasticity may account for the substantial discrepancy between structural changes and functional outcomes. [ABSTRACT FROM AUTHOR]- Published
- 2021
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14. Antibodies to MOG in CSF only: pathological findings support the diagnostic value.
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Carta, Sara, Höftberger, Romana, Bolzan, Anna, Bozzetti, Silvia, Bonetti, Bruno, Scarpelli, Mauro, Ottaviani, Sarah, Ghimenton, Claudio, Alberti, Daniela, Schanda, Kathrin, Reindl, Markus, Marignier, Romain, Ferrari, Sergio, and Mariotto, Sara
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CEREBROSPINAL fluid examination ,OLIGODENDROGLIA ,IMMUNOGLOBULINS ,MYELIN oligodendrocyte glycoprotein ,CENTRAL nervous system ,SPINAL cord ,NEUROLOGICAL disorders - Abstract
Scarce pathological brain evaluations confirmed the distinct entity of MOG-Abs-associated disorders (MOGAD), characterised by relative axonal sparing, perivenous, subpial, cortical and confluent primary demyelination, reactive gliosis, and inflammatory infiltrates predominantly constituted by granulocytes, macrophages, and CD4 + T cells [[2], [6]]. Spinal cord MRI showed multiple short T2-hyperintense lesions involving the spinal cord from the cranio-cervical junction to T12 and a central tumefactive lesion extending longitudinally from T9 to the conus (Fig. Antibodies to myelin oligodendrocyte glycoprotein (MOG-Abs) define a distinct entity of inflammatory CNS diseases, commonly presenting with subacute optic neuritis and/or myelitis in adults and encephalomyelitis in children [[5]]. We herein report the first autoptic findings of brain, spinal cord, nerve roots, and leptomeninges of a patient with MOG-Abs positivity in CSF only. [Extracted from the article]
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- 2021
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15. Serum GFAP and NfL as disease severity and prognostic biomarkers in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder.
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Schindler, Patrick, Grittner, Ulrike, Oechtering, Johanna, Leppert, David, Siebert, Nadja, Duchow, Ankelien S., Oertel, Frederike C., Asseyer, Susanna, Kuchling, Joseph, Zimmermann, Hanna G., Brandt, Alexander U., Benkert, Pascal, Reindl, Markus, Jarius, Sven, Paul, Friedemann, Bellmann-Strobl, Judith, Kuhle, Jens, and Ruprecht, Klemens
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NEUROMYELITIS optica ,GLIAL fibrillary acidic protein ,MYELIN oligodendrocyte glycoprotein ,PROGNOSIS - Abstract
Background: Neuromyelitis optica spectrum disorder (NMOSD) is a frequently disabling neuroinflammatory syndrome with a relapsing course. Blood-based disease severity and prognostic biomarkers for NMOSD are a yet unmet clinical need. Here, we evaluated serum glial fibrillary acidic protein (sGFAP) and neurofilament light (sNfL) as disease severity and prognostic biomarkers in patients with aquaporin-4 immunoglobulin (Ig)G positive (AQP4-IgG+) NMOSD.Methods: sGFAP and sNfL were determined by single-molecule array technology in a prospective cohort of 33 AQP4-IgG+ patients with NMOSD, 32 of which were in clinical remission at study baseline. Sixteen myelin oligodendrocyte glycoprotein IgG-positive (MOG-IgG+) patients and 38 healthy persons were included as controls. Attacks were recorded in all AQP4-IgG+ patients over a median observation period of 4.25 years.Results: In patients with AQP4-IgG+ NMOSD, median sGFAP (109.2 pg/ml) was non-significantly higher than in MOG-IgG+ patients (81.1 pg/ml; p = 0.83) and healthy controls (67.7 pg/ml; p = 0.07); sNfL did not substantially differ between groups. Yet, in AQP4-IgG+, but not MOG-IgG+ patients, higher sGFAP was associated with worse clinical disability scores, including the Expanded Disability Status Scale (EDSS, standardized effect size = 1.30, p = 0.007) and Multiple Sclerosis Functional Composite (MSFC, standardized effect size = - 1.28, p = 0.01). While in AQP4-IgG+, but not MOG-IgG+ patients, baseline sGFAP and sNfL were positively associated (standardized effect size = 2.24, p = 0.001), higher sNfL was only non-significantly associated with worse EDSS (standardized effect size = 1.09, p = 0.15) and MSFC (standardized effect size = - 1.75, p = 0.06) in patients with AQP4-IgG+ NMOSD. Patients with AQP4-IgG+ NMOSD with sGFAP > 90 pg/ml at baseline had a shorter time to a future attack than those with sGFAP ≤ 90 pg/ml (adjusted hazard ratio [95% confidence interval] = 11.6 [1.3-105.6], p = 0.03). In contrast, baseline sNfL levels above the 75th age adjusted percentile were not associated with a shorter time to a future attack in patients with AQP4-IgG+ NMOSD.Conclusion: These findings suggest a potential role for sGFAP as biomarker for disease severity and future disease activity in patients with AQP4-IgG+ NMOSD in phases of clinical remission. [ABSTRACT FROM AUTHOR]- Published
- 2021
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16. Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders
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Mader Simone, Gredler Viktoria, Schanda Kathrin, Rostasy Kevin, Dujmovic Irena, Pfaller Kristian, Lutterotti Andreas, Jarius Sven, Di Pauli Franziska, Kuenz Bettina, Ehling Rainer, Hegen Harald, Deisenhammer Florian, Aboul-Enein Fahmy, Storch Maria K, Koson Peter, Drulovic Jelena, Kristoferitsch Wolfgang, Berger Thomas, and Reindl Markus
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Neuromyelitis optica ,autoantibodies ,myelin oligodendrocyte glycoprotein ,aquaporin-4 ,complement mediated cytotoxicity ,biomarker ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Serum autoantibodies against the water channel aquaporin-4 (AQP4) are important diagnostic biomarkers and pathogenic factors for neuromyelitis optica (NMO). However, AQP4-IgG are absent in 5-40% of all NMO patients and the target of the autoimmune response in these patients is unknown. Since recent studies indicate that autoimmune responses to myelin oligodendrocyte glycoprotein (MOG) can induce an NMO-like disease in experimental animal models, we speculate that MOG might be an autoantigen in AQP4-IgG seronegative NMO. Although high-titer autoantibodies to human native MOG were mainly detected in a subgroup of pediatric acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) patients, their role in NMO and High-risk NMO (HR-NMO; recurrent optic neuritis-rON or longitudinally extensive transverse myelitis-LETM) remains unresolved. Results We analyzed patients with definite NMO (n = 45), HR-NMO (n = 53), ADEM (n = 33), clinically isolated syndromes presenting with myelitis or optic neuritis (CIS, n = 32), MS (n = 71) and controls (n = 101; 24 other neurological diseases-OND, 27 systemic lupus erythematosus-SLE and 50 healthy subjects) for serum IgG to MOG and AQP4. Furthermore, we investigated whether these antibodies can mediate complement dependent cytotoxicity (CDC). AQP4-IgG was found in patients with NMO (n = 43, 96%), HR-NMO (n = 32, 60%) and in one CIS patient (3%), but was absent in ADEM, MS and controls. High-titer MOG-IgG was found in patients with ADEM (n = 14, 42%), NMO (n = 3, 7%), HR-NMO (n = 7, 13%, 5 rON and 2 LETM), CIS (n = 2, 6%), MS (n = 2, 3%) and controls (n = 3, 3%, two SLE and one OND). Two of the three MOG-IgG positive NMO patients and all seven MOG-IgG positive HR-NMO patients were negative for AQP4-IgG. Thus, MOG-IgG were found in both AQP4-IgG seronegative NMO patients and seven of 21 (33%) AQP4-IgG negative HR-NMO patients. Antibodies to MOG and AQP4 were predominantly of the IgG1 subtype, and were able to mediate CDC at high-titer levels. Conclusions We could show for the first time that a subset of AQP4-IgG seronegative patients with NMO and HR-NMO exhibit a MOG-IgG mediated immune response, whereas MOG is not a target antigen in cases with an AQP4-directed humoral immune response.
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- 2011
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17. MOG-expressing teratoma followed by MOG-IgG-positive optic neuritis.
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Wildemann, Brigitte, Jarius, Sven, Franz, Jonas, Ruprecht, Klemens, Reindl, Markus, and Stadelmann, Christine
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OPTIC neuritis ,NEUROMYELITIS optica ,TERATOMA ,GLIAL fibrillary acidic protein ,MYELIN oligodendrocyte glycoprotein - Abstract
Keywords: Myelin oligodendrocyte glycoprotein (MOG); Antibodies; Optic neuritis; Ovarian teratoma EN Myelin oligodendrocyte glycoprotein (MOG) Antibodies Optic neuritis Ovarian teratoma 127 131 5 01/07/21 20210101 NES 210101 Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00401-020-02236-5) contains supplementary material, which is available to authorized users. A paraneoplastic etiology has been reported in few patients with aquaporin-4 (AQP4)-IgG-seropositive neuromyelitis optica spectrum disorders (NMOSD), with lung and breast cancer being the most frequent associated malignancies [[12]]. Cranial magnetic resonance imaging (MRI) revealed a normal optic nerve and a solitary small T2/fluid-attenuated inversion recovery lesion in the right frontal white matter; spinal MRI was unremarkable. [Extracted from the article]
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- 2021
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18. Serum MOG IgG titres should be performed routinely in the diagnosis and follow-up of MOGAD: Yes.
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Reindl, Markus and Rostasy, Kevin
- Subjects
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TITERS , *OPTIC neuritis , *IMMUNOGLOBULIN G , *HIV seroconversion , *NEUROMYELITIS optica , *MAGNETIC resonance imaging , *MYELIN oligodendrocyte glycoprotein - Abstract
Interestingly, no patient in our cohort suffered from a relapse after time of first seroconversion, although fluctuating MOG-IgG titres with increase after a period of low or even negative MOG-IgG titres were reported in selected patients. Likewise, onset serum MOG-IgG titres, despite being important for the diagnosis of MOGAD, do not predict recovery or relapse.[1],[7] In most patients MOG-IgG titres decline with time, but may also remain positive in other patients for years. [Extracted from the article]
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- 2023
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19. Recent developments in MOG-IgG associated neurological disorders.
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Hegen, Harald and Reindl, Markus
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In the past few years, acquired demyelinating syndromes of the central nervous system associated with antibodies against myelin oligodendrocyte glycoprotein (MOG) have evolved into a new inflammatory disease entity distinct from neuromyelitis optica spectrum disorders or multiple sclerosis. The meticulous clinical description of patients with MOG IgG antibodies (MOG-IgG) has been achieved by development and use of highly specific cell-based assays. MOG-IgG associated disorders comprise a wide spectrum of syndromes ranging from acute disseminated encephalomyelitis predominantly in children to optic neuritis or myelitis mostly in adults. In recent studies, phenotype of MOG-IgG associated disorders has further broadened with the description of cases of brainstem encephalitis, encephalitis with seizures and overlap syndromes with other types of autoimmune encephalitis. In this review, we provide an overview of current knowledge of MOG-IgG associated disorders, describe the clinical presentations identified, highlight differences from neuromyelitis optica spectrum disorders and multiple sclerosis, summarize clinical outcome and concepts of immune treatment, depict the underlying mechanisms of antibody pathogenicity and provide the methodological essentials of MOG-IgG assays. [ABSTRACT FROM AUTHOR]
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- 2020
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20. Comparative Analysis of T-Cell Responses to Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein in Inflammatory Demyelinating Central Nervous System Diseases.
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Hofer, Livia Sophie, Ramberger, Melanie, Gredler, Viktoria, Pescoller, Anna Sophie, Rostásy, Kevin, Sospedra, Mireia, Hegen, Harald, Berger, Thomas, Lutterotti, Andreas, and Reindl, Markus
- Subjects
MYELIN oligodendrocyte glycoprotein ,CENTRAL nervous system diseases ,NEUROMYELITIS optica ,MACROPHAGE colony-stimulating factor ,HLA histocompatibility antigens ,COMPARATIVE studies - Abstract
Autoantibodies against aquaporin-4 (AQP4-Ab) and myelin oligodendrocyte glycoprotein (MOG-Ab) are associated with rare central nervous system inflammatory demyelinating diseases like neuromyelitis optica spectrum disorders (NMOSD). Previous studies have shown that not only antibodies, but also autoreactive T-cell responses against AQP4 are present in NMOSD. However, no study has yet analyzed the presence of MOG reactive T-cells in patients with MOG antibodies. Therefore, we compared AQP4 and MOG specific peripheral T-cell response in individuals with AQP4-Ab (n = 8), MOG-Ab (n = 10), multiple sclerosis (MS, n = 8), and healthy controls (HC, n = 14). Peripheral blood mononuclear cell cultures were stimulated with eight AQP4 and nine MOG peptides selected from previous studies and a tetanus toxoid peptide mix as a positive control. Antigen-specific T-cell responses were assessed using the carboxyfluorescein diacetate succinimidyl ester proliferation assay and the detection of granulocyte macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-ɤ and interleukin (IL)-4, IL-6, and IL-17A in cell culture supernatants. Additionally, human leukocyte antigen (HLA)-DQ and HLA-DR genotyping of all participants was performed. We classified a T-cell response as positive if proliferation (measured by a cell division index ≥3) was confirmed by the secretion of at least one cytokine. Reactivity against AQP4 peptides was observed in many groups, but the T-cell response against AQP4 p156-170 was present only in patients with AQP4-Ab (4/8, 50%) and absent in patients with MOG-Ab, MS and HC (corrected p = 0.02). This AQP4 p156-170 peptide specific T-cell response was significantly increased in participants with AQP4-Ab compared to those without [Odds ratio (OR) = 59.00, 95% confidence interval-CI 2.70–1,290.86]. Moreover, T-cell responses against at least one AQP4 peptide were also more frequent in participants with AQP4-Ab (OR = 11.45, 95% CI 1.24–106.05). We did not observe any significant differences for the other AQP4 peptides or any MOG peptide. AQP4-Ab were associated with HLA DQB1
* 02 (OR = 5.71, 95% CI 1.09–30.07), DRB1* 01 (OR = 9.33, 95% CI 1.50–58.02) and DRB1* 03 (OR = 6.75, 95% CI = 1.19–38.41). Furthermore, HLA DRB1* 01 was also associated with the presence of AQP4 p156-170 reactive T-cells (OR = 31.67, 95% CI 1.30–772.98). To summarize, our findings suggest a role of AQP4-specific, but not MOG-specific T-cells, in NMOSD. [ABSTRACT FROM AUTHOR]- Published
- 2020
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21. Epidemiology of Pediatric NMOSD in Germany and Austria.
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Lechner, Christian, Breu, Markus, Wendel, Eva-Maria, Kornek, Barbara, Schanda, Kathrin, Baumann, Matthias, Reindl, Markus, and Rostásy, Kevin
- Subjects
NEUROMYELITIS optica ,AQUAPORINS ,MYELIN oligodendrocyte glycoprotein ,TRANSVERSE myelitis ,OPTIC neuritis ,CENTRAL nervous system - Abstract
Background: Neuromyelitis optica spectrum disorders (NMOSD) are severe inflammatory demyelinating disorders of the central nervous system mainly characterized by recurrent episodes of uni- or bilateral optic neuritis (ON), transverse myelitis (TM) and brainstem syndromes (BS). The majority of adult patients has serum antibodies directed against the water channel protein aquaporin 4 (AQP4-abs). In pediatric patients, AQP4-abs are less, while antibodies against myelin oligodendrocyte glycoprotein (MOG-abs) are more frequently detectable than in adults. Some children with NMOSD have neither AQP4- nor MOG-ab (double-seronegative). Objective: Evaluation of epidemiological data regarding incidence and prevalence of pediatric NMOSD in Germany and Austria. Methods: We recruited pediatric NMOSD patients between 1 March 2017 and 28 February 2019 with five different tools: (1) ESPED (Surveillance Unit for Rare Pediatric Disorders in Germany), (2) ESNEK (Surveillance for Rare Neurological Disorders during Childhood), (3) pediatric neurology working group within the Austrian Society of Pediatrics and Adolescent Medicine, (4) BIOMARKER Study and (5) NEMOS (Neuromyelitis optica Study Group). We requested data regarding clinical symptoms, antibody status, therapy regimen and response via a standardized questionnaire. Results: During the 2-year recruitment period, 46 (both incidental and prevalent) patients with a suspected diagnosis of NMOSD were brought to our attention. Twenty-two of these patients did not fulfill the inclusion criteria. Of the remaining 24 children, 22 had a median age at onset of 11 (range 3–17) years and 16/22 were female (72.7%) (no data in two patients). Sixteen of 24 patients were AQP4-ab positive (67%), 4/24 MOG-ab positive (16.7%), three children were double-seronegative and in one patient no antibody testing was done. We calculated an incidence rate of 0.022 per 100,000 person-years for Germany, while there was no incidental case in Austria during the recruitment period. The prevalence rate was 0.147 and 0.267 per 100,000 persons in Germany and Austria, respectively. Conclusion: Pediatric NMOSD, with and without associated antibodies, are very rare even considering the different limitations of our study. An unexpected finding was that a considerable proportion of patients was tested neither for AQP4- nor MOG-abs during diagnostic work-up, which should prompt to establish and disseminate appropriate guidelines. [ABSTRACT FROM AUTHOR]
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- 2020
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22. Failure of Expected Brain Growth in Children with ADEM.
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Baumgartner, Birgit, Bartels, Frederik, Wendel, Eva, Marquard, Klaus, Blaschek, Astrid, Karenfort, Michael, Baumann, Matthias, Cleaveland, Robert, Wegener-Panzer, Andreas, Reindl, Markus, Leiz, Steffen, Salandin, Michela, Krieg, Peter, Reindl, Tobias, Wentzell, Rüdiger, Finke, Carsten, and Rostáy, Kevin
- Subjects
NEURAL development ,GROWTH of children ,POSTVACCINAL encephalitis ,MYELIN oligodendrocyte glycoprotein - Published
- 2019
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23. Results of the ESPED Study "Neuromyelitis Optica Spectrum Disorders in Children and Adolescents.
- Author
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Lechner, Christian, Wendel, Eva-Maria, Breu, Markus, El Naggar, Ines, Schanda, Kathrin, Baumann, Matthias, Reindl, Markus, and Rostásy, Kevin
- Subjects
NEUROMYELITIS optica ,TEENAGERS ,MYELIN oligodendrocyte glycoprotein ,CHILDREN - Published
- 2019
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24. Myelin oligodendrocyte glycoprotein antibodies in neurological disease.
- Author
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Reindl, Markus and Waters, Patrick
- Subjects
- *
NEUROMYELITIS optica , *MYELIN oligodendrocyte glycoprotein , *POSTVACCINAL encephalitis , *OPTIC neuritis , *ADULT-child relationships , *ENCEPHALITIS - Abstract
Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies (MOG-Abs) were first detected by immunoblot and enzyme-linked immunosorbent assay nearly 30 years ago, but their association with multiple sclerosis (MS) was not specific. Use of cell-based assays with native MOG as the substrate enabled identification of a group of MOG-Ab-positive patients with demyelinating phenotypes. Initially, MOG-Abs were reported in children with acute disseminated encephalomyelitis (ADEM). Further studies identified MOG-Abs in adults and children with ADEM, seizures, encephalitis, anti-aquaporin-4-antibody (AQP4-Ab)-seronegative neuromyelitis optica spectrum disorder (NMOSD) and related syndromes (optic neuritis, myelitis and brainstem encephalitis), but rarely in MS. This shift in our understanding of the diagnostic assays has re-invigorated the examination of MOG-Abs and their role in autoimmune and demyelinating disorders of the CNS. The clinical phenotypes, disease courses and responses to treatment that are associated with MOG-Abs are currently being defined. MOG-Ab-associated disease is different to AQP4-Ab-positive NMOSD and MS. This Review provides an overview of the current knowledge of MOG, the metrics of MOG-Ab assays and the clinical associations identified. We collate the data on antibody pathogenicity and the mechanisms that are thought to underlie this. We also highlight differences between MOG-Ab-associated disease, NMOSD and MS, and describe our current understanding on how best to treat MOG-Ab-associated disease. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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25. MOG antibody seropositivity in a patient with encephalitis: beyond the classical syndrome.
- Author
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Mariotto, Sara, Monaco, Salvatore, Peschl, Patrick, Coledan, Ilaria, Mazzi, Romualdo, Höftberger, Romana, Reindl, Markus, and Ferrari, Sergio
- Subjects
MYELIN oligodendrocyte glycoprotein ,CENTRAL nervous system viral diseases ,ENCEPHALITIS ,MYELITIS ,NEURITIS - Abstract
Background: The presence of circulating anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) has been described in sera of patients with different inflammatory conditions of the central nervous system. In adults the core clinical feature is usually characterised by acute myelitis and/or optic neuritis. We here report an atypical case with serum and cerebrospinal fluid MOG-Abs and a clinical picture suggestive for acute encephalitis.Case Presentation: A 31-year-old Indian man presented with altered mental status, slight fever, and ataxia. Brain magnetic resonance imaging noted a widespread involvement of the white matter associated with slight cortical and subcortical damage in absence of contrast enhancement. An extensive infectious screening resulted negative while autoimmune analysis revealed the presence of MOG-Abs, detected with live cell-based assay. After treatment with intravenous immunoglobulins a marked and prompt clinical and radiological improvement was observed.Conclusions: To date, several areas of uncertainty still remain regarding clinical features and prognosis of subjects with MOG-Abs. The description of atypical cases is crucial, since recognition of this condition leads to prompt treatment and better prognosis, as in the case here reported. [ABSTRACT FROM AUTHOR]- Published
- 2017
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26. Guilty by association? SARS‐CoV‐2 antibodies and myelin oligodendrocyte glycoprotein antibody‐associated disease.
- Author
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Tanasescu, Radu and Reindl, Markus
- Subjects
- *
MYELIN oligodendrocyte glycoprotein , *SARS-CoV-2 , *NEUROMYELITIS optica , *IMMUNOGLOBULINS , *POSTVACCINAL encephalitis - Published
- 2022
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27. Myelin Oligodendrocyte Glycoprotein: Deciphering a Target in Inflammatory Demyelinating Diseases.
- Author
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Peschl, Patrick, Bradl, Monika, Höftberger, Romana, Berger, Thomas, and Reindl, Markus
- Subjects
MYELIN proteins ,OLIGODENDROGLIA ,DEMYELINATION - Abstract
Myelin oligodendrocyte glycoprotein (MOG), a member of the immunoglobulin (Ig) superfamily, is a myelin protein solely expressed at the outermost surface of myelin sheaths and oligodendrocyte membranes. This makes MOG a potential target of cellular and humoral immune responses in inflammatory demyelinating diseases. Due to its late postnatal developmental expression, MOG is an important marker for oligodendrocyte maturation. Discovered about 30 years ago, it is one of the best-studied autoantigens for experimental autoimmune models for multiple sclerosis (MS). Human studies, however, have yielded controversial results on the role of MOG, especially MOG antibodies (Abs), as a biomarker in MS. But with improved detection methods using different expression systems to detect Abs in patients' samples, this is meanwhile no longer the case. Using cell-based assays with recombinant full-length, conformationally intact MOG, several recent studies have revealed that MOG Abs can be found in a subset of predominantly pediatric patients with acute disseminated encephalomyelitis (ADEM), aquaporin-4 (AQP4) seronegative neuromyelitis optica spectrum disorders (NMOSD), monophasic or recurrent isolated optic neuritis (ON), or transverse myelitis, in atypical MS and in N-methyl-d-aspartate receptor-encephalitis with overlapping demyelinating syndromes. Whereas MOG Abs are only transiently observed in monophasic diseases such as ADEM and their decline is associated with a favorable outcome, they are persistent in multiphasic ADEM, NMOSD, recurrent ON, or myelitis. Due to distinct clinical features within these diseases it is controversially disputed to classify MOG Ab-positive cases as a new disease entity. Neuropathologically, the presence of MOG Abs is characterized by MS-typical demyelination and oligodendrocyte pathology associated with Abs and complement. However, it remains unclear whether MOG Abs are a mere inflammatory bystander effect or truly pathogenetic. This article provides deeper insight into recent developments, the clinical relevance of MOG Abs and their role in the immunpathogenesis of inflammatory demyelinating disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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28. Methodological Challenges in Protein Microarray and Immunohistochemistry for the Discovery of Novel Autoantibodies in Paediatric Acute Disseminated Encephalomyelitis.
- Author
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Peschl, Patrick, Ramberger, Melanie, Höftberger, Romana, Jöhrer, Karin, Baumann, Matthias, Rostásy, Kevin, and Reindl, Markus
- Subjects
POSTVACCINAL encephalitis ,PROTEIN microarrays ,IMMUNOHISTOCHEMISTRY techniques ,MYELIN oligodendrocyte glycoprotein ,IMMUNOGLOBULINS ,CHILD patients ,PATIENTS - Abstract
Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune-mediated demyelinating disease affecting mainly children and young adults. Differentiation to multiple sclerosis is not always possible, due to overlapping clinical symptoms and recurrent and multiphasic forms. Until now, immunoglobulins reactive to myelin oligodendrocyte glycoprotein (MOG antibodies) have been found in a subset of patients with ADEM. However, there are still patients lacking autoantibodies, necessitating the identification of new autoantibodies as biomarkers in those patients. Therefore, we aimed to identify novel autoantibody targets in ADEM patients. Sixteen ADEM patients (11 seronegative, 5 seropositive for MOG antibodies) were analysed for potential new biomarkers, using a protein microarray and immunohistochemistry on rat brain tissue to identify antibodies against intracellular and surface neuronal and glial antigens. Nine candidate antigens were identified in the protein microarray analysis in at least two patients per group. Immunohistochemistry on rat brain tissue did not reveal new target antigens. Although no new autoantibody targets could be found here, future studies should aim to identify new biomarkers for therapeutic and prognostic purposes. The microarray analysis and immunohistochemistry methods used here have several limitations, which should be considered in future searches for biomarkers. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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29. Children with multiphasic disseminated encephalomyelitis and antibodies to the myelin oligodendrocyte glycoprotein (MOG): Extending the spectrum of MOG antibody positive diseases.
- Author
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Baumann, Matthias, Strautmanis, Jurgis, Syrbe, Steffen, Vieker, Silvia, Höftberger, Romana, Rostásy, Kevin, Hennes, Eva-Maria, Schanda, Kathrin, Reindl, Markus, Karenfort, Michael, Kornek, Barbara, Seidl, Rainer, Diepold, Katharina, Lauffer, Heinz, and Marquardt, Iris
- Subjects
POSTVACCINAL encephalitis ,MYELIN oligodendrocyte glycoprotein ,JUVENILE diseases ,IMMUNOGLOBULINS ,MAGNETIC resonance imaging ,PATIENTS - Abstract
Background: Myelin oligodendrocyte glycoprotein (MOG) antibodies have been described in children with acute disseminated encephalomyelitis (ADEM), recurrent optic neuritis, neuromyelitis optica spectrum disorders and more recently in children with multiphasic disseminated encephalomyelitis (MDEM). Objective: To delineate the clinical, cerebrospinal fluid (CSF) and radiological features of paediatric MDEM with MOG antibodies. Methods: Clinical course, serum antibodies, CSF, magnetic resonance imaging (MRI) studies and outcome of paediatric MDEM patients were reviewed. Results: A total of 8 children with two or more episodes of ADEM were identified from a cohort of 295 children with acute demyelinating events. All children had persisting MOG antibodies (median titre: 1:1280). All ADEM episodes included encephalopathy, polyfocal neurological signs and a typical MRI. Apart from ADEM episodes, three children had further clinical attacks without encephalopathy. Median age at initial presentation was 3 years (range: 1–7 years) and median follow-up 4 years (range: 1–8 years). New ADEM episodes were associated with new neurological signs and new MRI lesions. Clinical outcome did range from normal (four of the eight) to mild or moderate impairment (four of the eight). A total of four children received monthly immunoglobulin treatment during the disease course. Conclusion: Children with MDEM and persisting MOG antibodies constitute a distinct entity of relapsing demyelinating events and extend the spectrum of MOG antibody–associated diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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30. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 4: Afferent visual system damage after optic neuritis in MOG-IgG-seropositive versus AQP4-IgG-seropositive patients.
- Author
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Pache, Florence, Zimmermann, Hanna, Mikolajczak, Janine, Schumacher, Sophie, Lacheta, Anna, Oertel, Frederike C., Bellmann-Strobl, Judith, Jarius, Sven, Wildemann, Brigitte, Reindl, Markus, Waldman, Amy, Soelberg, Kerstin, Asgari, Nasrin, Ringelstein, Marius, Aktas, Orhan, Gross, Nikolai, Buttmann, Mathias, Ach, Thomas, Ruprecht, Klemens, and Paul, Friedemann
- Subjects
MYELIN oligodendrocyte glycoprotein ,OPTIC neuritis ,VISION disorders ,OPTICAL coherence tomography ,HEALTH outcome assessment ,VISUAL evoked potentials ,VISUAL acuity ,PATIENTS ,DIAGNOSIS - Abstract
Background: Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been reported in patients with aquaporin-4 antibody (AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD). The objective of this study was to describe optic neuritis (ON)-induced neuro-axonal damage in the retina of MOG-IgG-positive patients in comparison with AQP4-IgG-positive NMOSD patients. Methods: Afferent visual system damage following ON was bilaterally assessed in 16 MOG-IgG-positive patients with a history of ON and compared with that in 16 AQP4-IgG-positive NMOSD patients. In addition, 16 healthy controls matched for age, sex, and disease duration were analyzed. Study data included ON history, retinal optical coherence tomography, visual acuity, and visual evoked potentials. Results: Eight MOG-IgG-positive patients had a previous diagnosis of AQP4-IgG-negative NMOSD with ON and myelitis, and eight of (mainly recurrent) ON. Twenty-nine of the 32 eyes of the MOG-IgG-positive patients had been affected by at least one episode of ON. Peripapillary retinal nerve fiber layer thickness (pRNFL) and ganglion cell and inner plexiform layer volume (GCIP) were significantly reduced in ON eyes of MOG-IgG-positive patients (pRNFL = 59 ± 23 μm; GCIP = 1.50 ± 0.34 mm3) compared with healthy controls (pRNFL = 99 ± 6 μm, p < 0.001; GCIP =1.97 ± 0.11 mm3, p < 0.001). Visual acuity was impaired in eyes after ON in MOG-IgG-positive patients (0.35 ± 0.88 logMAR). There were no significant differences in any structural or functional visual parameters between MOG-IgGpositive and AQP4-IgG-positive patients (pRNFL: 59 ± 21 μm; GCIP: 1.41 ± 0.27 mm3; Visual acuity = 0.72 ± 1.09 logMAR). Importantly, MOG-IgG-positive patients had a significantly higher annual ON relapse rate than AQP4-IgGpositive patients (median 0.69 vs. 0.29 attacks/year, p = 0.004), meaning that on average a single ON episode caused less damage in MOG-IgG-positive than in AQP4-IgG-positive patients. pRNFL and GCIP loss correlated with the number of ON episodes in MOG-IgG-positive patients (p < 0.001), but not in AQP4-IgG-positive patients. Conclusions: Retinal neuro-axonal damage and visual impairment after ON in MOG-IgG-positive patients are as severe as in AQP4-IgG-positive NMOSD patients. In MOG-IgG-positive patients, damage accrual may be driven by higher relapse rates, whereas AQP4-IgG-positive patients showed fewer but more severe episodes of ON. Given the marked damage in some of our MOG-IgG-positive patients, early diagnosis and timely initiation and close monitoring of immunosuppressive therapy are important. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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31. Screening for MOG-IgG and 27 other anti-glial and anti-neuronal autoantibodies in ‘pattern II multiple sclerosis’ and brain biopsy findings in a MOG-IgG-positive case.
- Author
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Jarius, Sven, Metz, Imke, König, Fatima Barbara, Ruprecht, Klemens, Reindl, Markus, Paul, Friedemann, Brück, Wolfgang, and Wildemann, Brigitte
- Subjects
MYELIN oligodendrocyte glycoprotein ,MEDICAL screening ,MULTIPLE sclerosis ,AUTOANTIBODIES ,GLUTAMATE receptors ,HISTOPATHOLOGY ,IMMUNOLOGY - Abstract
Background: Histopathological studies have revealed four different immunopathological patterns of lesion pathology in early multiple sclerosis (MS). Pattern II MS is characterised by immunoglobulin and complement deposition in addition to T-cell and macrophage infiltration and is more likely to respond to plasma exchange therapy, suggesting a contribution of autoantibodies. Objective: To assess the frequency of anti-myelin oligodendrocyte glycoprotein (MOG), anti-M1-aquaporin-4 (AQP4), anti-M23-AQP4, anti-N-methyl-d-aspartate-type glutamate receptors (NMDAR) and 25 other anti-neural antibodies in pattern II MS. Methods: Thirty-nine serum samples from patients with MS who had undergone brain biopsy (n = 24; including 13 from patients with pattern II MS) and from histopathologically non-classified MS patients (n = 15) were tested for anti-MOG, anti-M1-AQP4, anti-M23-AQP4, anti-NMDAR, anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-type glutamate receptors (AMPAR), anti-gamma-aminobutyric acid receptors (GABA
B R), anti-leucine-rich, glioma-activated protein 1 (LGI1), anti-contactin-associated protein 2 (CASPR2), anti-dipeptidyl-peptidase-like protein-6 (DPPX), anti-Tr/Delta/notch-like epidermal growth factor–related receptor (DNER), anti-Hu, anti-Yo, anti-Ri, anti-Ma1/Ma2, anti-CV2/collapsin response mediator protein 5 (CRMP5), anti-glutamic acid decarboxylase (GAD), anti-amphiphysin, anti-Ca/RhoGTPase-activating protein 26 (ARHGAP26), anti-Sj/inositol-1,4,5-trisphosphate receptor 1 (ITPR1), anti-Homer3, anti-carbonic anhydrase–related protein (CARPVIII), anti-protein kinase gamma (PKCgamma), anti-glutamate receptor delta 2 (GluRdelta2), anti-metabotropic glutamate receptor 1 (mGluR1) and anti-mGluR5, as well as for anti-glial nuclei antibodies (AGNA) and Purkinje cell antibody 2 (PCA2). Results: Antibodies to MOG belonging to the complement-activating immunoglobulin G1 (IgG1) subclass were detected in a patient with pattern II MS. Detailed brain biopsy findings are shown. Conclusion: This is the largest study on established anti-neural antibodies performed in MS so far. MOG-IgG may play a role in a small percentage of patients diagnosed with pattern II MS. [ABSTRACT FROM AUTHOR]- Published
- 2016
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32. Leptomeningeal and Intraparenchymal Blood Barrier Disruption in a MOG-IgG Positive Patient.
- Author
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Mohseni, Sayed Hamid, Skejoe, Hanne Pernille Bro, Wuerfel, Jens, Paul, Friedemann, Reindl, Markus, Jarius, Sven, and Asgari, Nasrin
- Subjects
MYELIN oligodendrocyte glycoprotein ,MYELIN sheath diseases ,SPINAL nerves ,BLOOD-brain barrier ,CENTRAL nervous system diseases ,BLOOD sampling - Abstract
Background. A serum immunoglobulin G (IgG) autoantibody specific for the myelin oligodendrocyte glycoprotein (MOG) is detected in the subgroup patients with inflammatory demyelinating diseases of the central nervous system (CNS). However, whether MOG-IgG contributes to blood-brain barrier (BBB) impairment remains poorly characterized. Findings. We report a 30-year-old previously healthy female who presented with attacks on the optic nerves and a demyelinating spinal cord lesion, in which the blood–CNS barriers including leptomeningeal blood barrier and BBB were altered, as demonstrated by gadolinium-enhanced MRI during relapse. Blood samples taken at onset and four years later were retrospectively found positive for MOG-IgG. Conclusion. Our findings demonstrate that MRI-detected leptomeningeal enhancement occurs in MOG-IgG positive patients, accompanying intraparenchymal BBB breakdown during attack. The findings suggest that meningeal inflammation occurs following MOG-IgG-related parenchymal inflammation. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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33. Clinical spectrum associated with MOG autoimmunity in adults: significance of sharing rodent MOG epitopes.
- Author
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Sepúlveda, Maria, Armangue, Thaís, Martinez-Hernandez, Eugenia, Arrambide, Georgina, Sola-Valls, Nuria, Sabater, Lidia, Téllez, Nieves, Midaglia, Luciana, Ariño, Helena, Peschl, Patrick, Reindl, Markus, Rovira, Alex, Montalban, Xavier, Blanco, Yolanda, Dalmau, Josep, Graus, Francesc, and Saiz, Albert
- Subjects
MYELIN oligodendrocyte glycoprotein ,AUTOIMMUNITY ,EPITOPES ,NEUROMYELITIS optica ,IMMUNOHISTOCHEMISTRY ,MAGNETIC resonance imaging - Abstract
The aim of this study was to report the clinical spectrum associated with antibodies to myelin oligodendrocyte glycoprotein (MOG) in adult patients, and to assess whether phenotypic variants are dependent on recognition of rodent MOG epitopes. We retrospectively analyzed the features, course and outcome of 56 patients whose samples were investigated by brain tissue immunohistochemistry and cell-based assays using human and rodent MOG. The median age at symptom onset was 37 years (range 18-70); 35 patients (63 %) were female. After a median follow-up of 43 months (range 4-554), only 14 patients (25 %) developed a neuromyelitis optica spectrum disorder (NMOSD), 27 patients (47 %) retained the initial diagnosis of isolated optic neuritis, 7 (12 %) of longitudinally extensive transverse myelitis, and 2 (4 %) of acute disseminated encephalomyelitis; 6 patients (11 %) developed atypical demyelinating syndromes (4 had relapsing episodes of short myelitis lesions which in one occurred with optic neuritis; 1 had relapsing brainstem symptoms, and 1 relapsing demyelinating encephalomyelitis). The course was frequently associated with relapses (71 %) and good outcome. Twenty-seven patients (49 %) had antibodies that recognized rodent MOG epitopes, and 9 of them (16 %) showed a myelin staining pattern in rodent tissue. Only the myelin staining pattern was linked to NMOSD ( p = 0.005). In conclusion, MOG autoimmunity in adult patients associates with a clinical spectrum wider than the one expected for patients with suspected NMOSD and overall good outcome. Antibodies to rodent MOG epitopes do not associate with any phenotypic variant. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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34. Antibodies to MOG and AQP4 in adults with neuromyelitis optica and suspected limited forms of the disease.
- Author
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Höftberger, Romana, Sepulveda, María, Armangue, Thaís, Blanco, Yolanda, Rostásy, Kevin, Cobo Calvo, Alvaro, Olascoaga, Javier, Ramió-Torrentà, Lluís, Reindl, Markus, Benito-León, Julián, Casanova, Bonaventura, Arrambide, Georgina, Sabater, Lidia, Graus, Francesc, Dalmau, Josep, and Saiz, Albert
- Subjects
NEUROMYELITIS optica ,IMMUNOGLOBULINS ,MYELIN oligodendrocyte glycoprotein ,AQUAPORINS ,OLDER patients ,BIOLOGICAL assay ,MANN Whitney U Test ,CHI-squared test ,DISEASES - Abstract
The article presents a study which examines the frequency and implications of antibodies to myelin oligodendrocyte glycoprotein (MOG-ab) and aquaporin 4 antibodies (AQP4-ab) in adult patients with suspected limited forms of neuromyelitis optica (NMO). The study is investigated by cell-based assays, Mann-Whitney U test, and Chi-square test. Results show that MOG-ab is commonly detected in the serum of patients with NMO, longitudinally extensive myelitis (LETM), and optic neuritis (ON).
- Published
- 2015
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35. The spectrum of MOG autoantibody-associated demyelinating diseases.
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Reindl, Markus, Di Pauli, Franziska, Rostãsy, Kevin, and Berger, Thomas
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MYELIN oligodendrocyte glycoprotein , *AUTOANTIBODIES , *ANIMAL models in research , *ANIMAL models of multiple sclerosis , *ENCEPHALOMYELITIS - Abstract
Myelin oligodendrocyte glycoprotein (MOG) has been identified as a target of demyelinating autoantibodies in animal models of inflammatory demyelinating diseases of the CNS, such as multiple sclerosis (MS). Numerous studies have aimed to establish a role for MOG antibodies in patients with MS, although the results have been controversial. Cell-based immunoassays using MOG expressed in mammalian cells have demonstrated the presence of high-titre MOG antibodies in paediatric patients with acute disseminated encephalomyelitis, MS. aquaporin-4-seronegative neuromyelitis optica, or isolated optic neuritis or transverse myelitis, but only rarely in adults with these disorders. These studies indicate that MOG antibodies could be associated with a broad spectrum of acquired human CNS demyelinating diseases. This Review article discusses the current I terature on MOG antibodies, their potential clinical relevance, and their role in the pathogenesis of MOG antibody-associated demyelinating disorders. [ABSTRACT FROM AUTHOR]
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- 2013
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36. Epitope specificity of serum antibodies directed against the extracellular domain of myelin oligodendrocyte glycoprotein: Influence of relapses and immunomodulatory treatments
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Khalil, Michael, Reindl, Markus, Lutterotti, Andreas, Kuenz, Bettina, Ehling, Rainer, Gneiss, Claudia, Lackner, Peter, Deisenhammer, Florian, and Berger, Thomas
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EPITOPES , *MULTIPLE sclerosis , *GLYCOPROTEINS , *RESEARCH methodology , *IMMUNOLOGICAL adjuvants - Abstract
Abstract: Only few reports are available on the epitope specificity of anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in multiple sclerosis (MS). In the present study we provide a precise characterization of the epitope specificity of serum antibodies directed against the extracellular domain of MOG, including IgG, IgM and IgA immunoglobulin isotypes in 28 relapsing remitting MS patients and report that linear epitopes amino-acid (aa) 37–48 and aa42–53 are immunodominant. Recently experienced relapses intensified the anti-MOG peptide antibody response. Immunomodulatory treatment with interferon-beta or glatiramer-acetate had no major impact on the anti-MOG peptide immunoreactivity after 1year of therapy. [Copyright &y& Elsevier]
- Published
- 2006
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37. Optical coherence tomography in myelin-oligodendrocyte-glycoprotein antibody-seropositive patients: a longitudinal study.
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Oertel, Frederike C., Outteryck, Olivier, Knier, Benjamin, Zimmermann, Hanna, Borisow, Nadja, Bellmann-Strobl, Judith, Blaschek, Astrid, Jarius, Sven, Reindl, Markus, Ruprecht, Klemens, Meinl, Edgar, Hohlfeld, Reinhard, Paul, Friedemann, Brandt, Alexander U., Kümpfel, Tania, and Havla, Joachim
- Subjects
OPTICAL coherence tomography ,MYELIN oligodendrocyte glycoprotein ,OPTIC neuritis ,VISUAL acuity ,NERVE fibers - Abstract
Background: Serum antibodies against myelin-oligodendrocyte-glycoprotein (MOG-IgG) are detectable in a proportion of patients with acute or relapsing neuroinflammation. It is unclear, if neuro-axonal damage occurs only in an attack-dependent manner or also progressively. Therefore, this study aimed to investigate longitudinally intra-retinal layer changes in eyes without new optic neuritis (ON) in MOG-IgG-seropositive patients.Methods: We included 38 eyes of 24 patients without ON during follow-up (F/U) [median years (IQR)] 1.9 (1.0-2.2) and 56 eyes of 28 age- and sex-matched healthy controls (HC). The patient group's eyes included 18 eyes without (EyeON-) and 20 eyes with history of ON (EyeON+). Using spectral domain optical coherence tomography (OCT), we acquired peripapillary retinal nerve fiber layer thickness (pRNFL) and volumes of combined ganglion cell and inner plexiform layer (GCIP), inner nuclear layer (INL), and macular volume (MV). High-contrast visual acuity (VA) was assessed at baseline.Results: At baseline in EyeON-, pRNFL (94.3 ± 15.9 μm, p = 0.36), INL (0.26 ± 0.03 mm3, p = 0.11), and MV (2.34 ± 0.11 mm3, p = 0.29) were not reduced compared to HC; GCIP showed thinning (0.57 ± 0.07 mm3; p = 0.008), and VA was reduced (logMAR 0.05 ± 0.15 vs. - 0.09 ± 0.14, p = 0.008) in comparison to HC. Longitudinally, we observed pRNFL thinning in models including all patient eyes (annual reduction - 2.20 ± 4.29 μm vs. - 0.35 ± 1.17 μm, p = 0.009) in comparison to HC. Twelve EyeON- with other than ipsilateral ON attacks ≤ 6 months before baseline showed thicker pRNFL at baseline and more severe pRNFL thinning in comparison to 6 EyeON- without other clinical relapses.Conclusions: We observed pRNFL thinning in patients with MOG-IgG during F/U, which was not accompanied by progressive GCIP reduction. This effect could be caused by a small number of EyeON- with other than ipsilateral ON attacks within 6 months before baseline. One possible interpretation could be a reduction of the swelling, which could mean that MOG-IgG patients show immune-related swelling in the CNS also outside of an attack's target area. [ABSTRACT FROM AUTHOR]- Published
- 2019
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38. Clinical course of MOG antibody-associated recurrent demyelinating diseases.
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Reindl, Markus
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DEMYELINATION ,MYELIN oligodendrocyte glycoprotein ,OPTIC neuritis ,IMMUNOGLOBULINS ,POSTVACCINAL encephalitis ,INFLAMMATION - Published
- 2018
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39. Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria.
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Banwell, Brenda, Bennett, Jeffrey L, Marignier, Romain, Kim, Ho Jin, Brilot, Fabienne, Flanagan, Eoin P, Ramanathan, Sudarshini, Waters, Patrick, Tenembaum, Silvia, Graves, Jennifer S, Chitnis, Tanuja, Brandt, Alexander U, Hemingway, Cheryl, Neuteboom, Rinze, Pandit, Lekha, Reindl, Markus, Saiz, Albert, Sato, Douglas Kazutoshi, Rostasy, Kevin, and Paul, Friedemann
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NEUROMYELITIS optica , *MYELIN oligodendrocyte glycoprotein , *POSTVACCINAL encephalitis , *DEMYELINATION , *CONSENSUS (Social sciences) , *TRANSVERSE myelitis - Abstract
Serum antibodies directed against myelin oligodendrocyte glycoprotein (MOG) are found in patients with acquired CNS demyelinating syndromes that are distinct from multiple sclerosis and aquaporin-4-seropositive neuromyelitis optica spectrum disorder. Based on an extensive literature review and a structured consensus process, we propose diagnostic criteria for MOG antibody-associated disease (MOGAD) in which the presence of MOG-IgG is a core criterion. According to our proposed criteria, MOGAD is typically associated with acute disseminated encephalomyelitis, optic neuritis, or transverse myelitis, and is less commonly associated with cerebral cortical encephalitis, brainstem presentations, or cerebellar presentations. MOGAD can present as either a monophasic or relapsing disease course, and MOG-IgG cell-based assays are important for diagnostic accuracy. Diagnoses such as multiple sclerosis need to be excluded, but not all patients with multiple sclerosis should undergo screening for MOG-IgG. These proposed diagnostic criteria require validation but have the potential to improve identification of individuals with MOGAD, which is essential to define long-term clinical outcomes, refine inclusion criteria for clinical trials, and identify predictors of a relapsing versus a monophasic disease course. [ABSTRACT FROM AUTHOR]
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- 2023
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40. Distinction and Temporal Stability of Conformational Epitopes on Myelin Oligodendrocyte Glycoprotein Recognized by Patients with Different Inflammatory Central Nervous System Diseases.
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Mayer, Marie C., Breithaupt, Constanze, Reindl, Markus, Schanda, Kathrin, Rostásy, Kevin, Berger, Thomas, Dale, Russell C., Brilot, Fabienne, Olsson, Tomas, Jenne, Dieter, Pröbstel, Anne-Katrin, Dornmair, Klaus, Wekerle, Hartmut, Hohlfeld, Reinhard, Banwell, Brenda, Bar-Or, Amit, and Meinl, Edgar
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CENTRAL nervous system diseases , *MYELIN oligodendrocyte glycoprotein , *EPITOPES , *NEUROMYELITIS optica , *IMMUNOGLOBULIN G , *AQUAPORINS - Abstract
Autoantibodies targeting conformationally intact myelin oligodendrocyte glycoprotein (MOG) are found in different inflammatory diseases of the CNS, but their antigenic epitopes have not been mapped. We expressed mutants of MOG on human HeLa cells and analyzed sera from 111 patients (104 children, 7 adults) who recognized cell-bound human MOG, but had different diseases, including acute disseminated encephalomyelitis (ADEM), one episode of transverse myelitis or optic neuritis, multiple sclerosis (MS), anti-aquaporin-4 (AQP4)-negative neuromyelitis optica (NMO), and chronic relapsing inflammatory optic neuritis (CRION). We obtained insight into the recognition of epitopes in 98 patients. All epitopes identified were located at loops connecting the β strands of MOG. The most frequently recognized MOG epitope was revealed by the P42S mutation positioned in the CC'-loop. Overall, we distinguished seven epitope patterns, including the one mainly recognized by mouse mAbs. In half of the patients, the anti-MOG response was directed to a single epitope. The epitope specificity was not linked to certain disease entities. Longitudinal analysis of 11 patients for up to 5 y indicated constant epitope recognition without evidence for intramolecular epitope spreading. Patients who rapidly lost their anti-MOG IgG still generated a long-lasting IgG response to vaccines, indicating that their loss of anti-MOG reactivity did not reflect a general lack of capacity for long-standing IgG responses. The majority of human anti-MOG Abs did not recognize rodent MOG, which has implications for animal studies. Our findings might assist in future detection of potential mimotopes and pave the way to Ag-specific depletion. [ABSTRACT FROM AUTHOR]
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- 2013
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41. Neuromyelitis optica spectrum disorders with antibodies to myelin oligodendrocyte glycoprotein or aquaporin-4: Clinical and paraclinical characteristics in Algerian patients.
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Bouzar, Melissa, Daoudi, Smail, Hattab, Samira, Bouzar, Amel A., Deiva, Kumaran, Wildemann, Brigitte, Reindl, Markus, and Jarius, Sven
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NEUROMYELITIS optica , *MYELIN oligodendrocyte glycoprotein , *AQUAPORIN genetics , *IMMUNOGLOBULINS , *CENTRAL nervous system diseases , *OPTIC neuritis - Abstract
Background Neuromyelitis optica (NMO) is a severe autoimmune inflammatory disorder of the central nervous system. NMO and its abortive forms are referred to as NMO spectrum disorders (NMOSD). NMOSD are mostly associated with antibodies to aquaporin-4 (AQP4-IgG). However, recent studies have demonstrated antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) in a subset of patients. Data on NMOSD in North Africa are sparse. Objective To describe the frequency of MOG-IgG and AQP4-IgG among patients with optic neuritis (ON) and/or myelitis in Algeria as well as the clinical and paraclinical features associated with these antibodies. Methods Retrospective testing of 42 patients with optic neuritis and/or myelitis treated at the teaching hospital of TiziOuzou for MOG-IgG and AQP4-IgG, and retrospective evaluation of the patients' medical records. Results Six of 42 (14.3%) patients were positive for AQP4-IgG and 3/42 (7.1%) were positive for MOG-IgG. No patient was positive for both AQP4-IgG and MOG-IgG. All antibody-positive patients were women. MOG-IgG was associated with severe episodes of ON in all MOG-IgG-positive patients. Steroid treatment was followed by complete remission in two patients. AQP4-IgG was associated with ON and/or longitudinally extensive transverse myelitis (LETM), often with severe onset. While all six of the AQP4-IgG-positive patients met the 2015 IPND criteria for NMOSD, only one of the three MOG-IgG-positive patients did so. Interestingly, clinically silent extensive spinal cord or brain lesions were present in two of the three MOG-IgG-positive patients, and altered visual evoked potentials without clinical evidence of ON were found in three of the six AQP4-IgG-positive patients. Conclusion MOG-IgG and AQP4-IgG are found in a substantial subset of Algerian patients with ON and/or myelitis, are present predominantly in women, and may be associated with differences in clinical presentation and, possibly, outcome. Only a subset of MOG-IgG positive patients meets the current diagnostic criteria for NMOSD. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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42. Temporal dynamics of anti-MOG antibodies in CNS demyelinating diseases
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Di Pauli, Franziska, Mader, Simone, Rostasy, Kevin, Schanda, Kathrin, Bajer-Kornek, Barbara, Ehling, Rainer, Deisenhammer, Florian, Reindl, Markus, and Berger, Thomas
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DEMYELINATION , *MULTIPLE sclerosis , *CEREBROSPINAL fluid , *GLYCOPROTEINS , *AUTOANTIBODIES , *POSTVACCINAL encephalitis , *CENTRAL nervous system , *ENCEPHALOMYELITIS - Abstract
Abstract: Recent studies demonstrated the presence of autoantibodies to native myelin oligodendrocyte glycoprotein (MOG) in juvenile patients with acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS). However, so far no longitudinal studies on anti-MOG antibodies have been performed. Therefore, we determined serum and CSF antibodies against native human MOG in 266 pediatric and adult subjects with ADEM, clinically isolated syndrome (CIS), MS, other neurological diseases (OND) and healthy controls (HC) and longitudinal samples of 25 patients with ADEM, CIS, MS and OND using an immunofluorescence assay. We detected serum high-titer MOG IgG in 15/34 (44%) patients with ADEM, but only rarely in CIS (3/38, 8%), MS (2/89, 2%), OND (1/58, 2%) and HC (0/47). Longitudinal analysis of serum anti-MOG IgG showed different temporal dynamics of serum antibody responses in ADEM, CIS and MS and indicated an association of a favorable clinical outcome in ADEM with a decrease in antibody titers over time. [Copyright &y& Elsevier]
- Published
- 2011
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43. Diagnostic features of initial demyelinating events associated with serum MOG-IgG.
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Orlandi, Riccardo, Mariotto, Sara, Ferrari, Sergio, Gobbin, Francesca, Sechi, Elia, Capra, Ruggero, Mancinelli, Chiara Rosa, Bombardi, Roberto, Zuliani, Luigi, Zoccarato, Marco, Rossi, Francesca, Camera, Valentina, Ferraro, Diana, Benedetti, Maria Donata, Reindl, Markus, and Gajofatto, Alberto
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MYELIN oligodendrocyte glycoprotein , *NEUROMYELITIS optica , *OPTIC neuritis , *OPTIC nerve , *NEUROLOGICAL disorders , *SERUM - Abstract
Myelin oligodendrocyte glycoprotein (MOG)-IgG associated disorders are increasingly recognized as a distinct disease entity. However, diagnostic sensitivity and specificity of serum MOG-IgG as well as recommendations for testing are still debated. Between October 2015 and July 2017 we tested serum MOG-IgG in 91 adult patients (49 females) with a demyelinating event (DE) not fulfilling 2010 McDonald criteria for MS at sampling, negative for neuromyelitis optica (NMO)-IgG and followed-up for at least 12 months. We assessed the sensitivity and specificity of a live-cell MOG-IgG assay for each final diagnosis at last follow-up, for the 2018 international recommendations for MOG-IgG testing, and for other combinations of clinical and laboratory characteristics. Clinical presentations included acute myelitis (n = 48), optic neuritis (n = 36), multifocal encephalomyelitis (n = 4), and brainstem syndrome (n = 3). Twenty-four patients were MOG-IgG positive. Sensitivity and specificity of MOG-IgG test applied to the 2018 international recommendations were 28.4% and 86.7%, while they were 42.1% and 88.6% when applied to DE of unclear aetiology as defined above with two or more among: 1_no periventricular and juxtacortical MS-like lesions on brain MRI; 2_longitudinally extensive MRI optic nerve lesion; 3_no CSF-restricted oligoclonal bands; 4_CSF protein > 50 mg/dl. Simplified requirements compared to those currently proposed for MOG-IgG testing could facilitate the applicability of the assay in the diagnosis of adults with DEs of unclear aetiology. Unlabelled Image • There's still uncertainty about diagnostic sensitivity and specificity of serum MOG-IgG • This is an observational study including 91 patients with a demyelinaing event of unclear aetiology, 24 MOG-IgG positive • We evaluated sensitivity and specificity of simplified requirements for MOG-IgG testing • These requirements are easily applicable compared to previous indications for testing [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
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