PURPOSE OF REVIEW: This review summarizes recent insights into the pathogenesis and therapeutic options for patients with MOG- or AQP4-antibodies. RECENT FINDINGS: Although AQP4-IgG are linked to NMOSD, MOG-IgG-associated diseases (MOGAD) include a broader clinical spectrum of autoimmune brain disease. Details of membrane assembly of AQP4-IgG required for complement activation have been uncovered. Affinity-purified MOG-IgG from patients were shown to be pathogenic by induction of demyelination when the blood--brain barrier (BBB) was breached and by enhancement of activation of cognate T cells. A high-affinity AQP4-IgG, given peripherally, could induce NMOSD-like lesions in rats in the absence of BBB breach. Circulating AQP4-specific and MOG-specific B cells were identified and suggest differences in origin of MOG-antibodies or AQP4-antibodies. Patients with MOG-IgG show a dichotomy concerning circulating MOG-specific B cells; whether this is related to differences in clinical response of anti-CD20 therapy remains to be analyzed. Clinical trials of AQP4-IgG-positive NMOSD patients showed success with eculizumab (preventing cleavage of complement factor C5, thereby blocking formation of chemotactic C5a and membrane attack complex C9neo), inebilizumab (depleting CD19 + B cells), and satralizumab (anti-IL-6R blocking IL-6 actions). SUMMARY: New insights into pathological mechanisms and therapeutic responses argue to consider NMOSD with AQP4-IgG and MOGAD as separate brain disease entities.
#1Elias S. Sotirchos(JHUSOM: Johns Hopkins University School of Medicine)H-Index: 18
#2Angeliki Filippatou(JHUSOM: Johns Hopkins University School of Medicine)H-Index: 9
Last. Shiv Saidha(JHUSOM: Johns Hopkins University School of Medicine)H-Index: 28
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Background:Comparative studies of characteristics of optic neuritis (ON) associated with myelin oligodendrocyte glycoprotein-IgG (MOG-ON) and aquaporin-4-IgG (AQP4-ON) seropositivity are limited.Ob...
#1Miki Kojima(Saitama Medical University)H-Index: 2
#2Satoru Oji(Saitama Medical University)H-Index: 8
Last. Kyoichi Nomura(Saitama Medical University)H-Index: 10
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Abstract Background Neuromyelitis optica spectrum disorders (NMOSD) are a group of inflammatory central nervous system disorders characterized by optic neuritis, transverse myelitis, and anti-aquaporin 4 (AQP4) antibody production. However, it has recently been shown that some cases of typical NMOSD can be anti-AQP4 antibody-negative as well. In this study, we retrospectively investigated the disorder relapse-suppressing effect of tacrolimus (TAC) when combined with prednisolone (PSL) in anti-AQ...
Last. Ilya Kister(NYU: New York University)H-Index: 27
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Abstract Background Tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin-6 receptor, is approved for treatment of rheumatoid arthritis and several other immune-mediated disorders. Off-label use of the intravenous formulation of tocilizumab for Neuromyelitis Optica Spectrum Disorder (NMOSD) decreased relapse rates in two small case series. However, treatment protocol that requires frequent intravenous infusions may adversely affect adherence to therapy, especially in the mor...
Last. Kazuo Fujihara(Fukushima Medical University)H-Index: 71
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Abstract Introduction Neuromyelitis optica spectrum disorder (NMOSD) is characterized by the presence of serum anti-aquaporin 4 (AQP4) antibody. However, the significance of changes in the serum titer as a marker of disease severity or relapse prediction is unknown. Methods We collected clinical data and serum antibody titers by cell-based assay from 45 NMOSD patients for whom more than one titer measurement taken in 6–12 month interval periods was available. The AQP4-IgG titer was measured by a...
Objective To address the frequency of myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) in an unselected large cohort of adults with MS. Methods This is a cross-sectional study in 2 MS expert centers (Lyon and Strasbourg University Hospitals, France) between December 1, 2017, and June 31, 2018. Patients aged ≥18 years with a definite diagnosis of MS according to 2010 McDonald criteria were tested for MOG-Ab by using a cell-based assay (CBA) in Lyon and subsequently included. Positive sampl...
OBJECTIVE: To compare response to rituximab (RTX) between adult patients positive for myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibodies. METHODS: We prospectively studied adult patients with MOG or AQP4 antibodies who received RTX under an individualized dosing schedule adapted to the biological effect of RTX monitored by memory B-cell measurement. Memory B cells were counted monthly and when relapse occurred. The biological effect of RTX was considered significant with...
Last. Izlem Izbudak(Johns Hopkins University)H-Index: 19
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Background:MOG antibody and AQP4 antibody seropositive diseases are immunologically distinct subtypes of neuromyelitis optica spectrum disorders (NMOSD) with similar clinical presentations. MRI fin...
Myelin oligodendrocyte glycoprotein-IgG is a biomarker associated with CNS demyelinating diseases.1,2 MOGAD and aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG + NMOSD) have overlapping clinical features including optic neuritis and myelitis. However, there are several clinical and radiologic distinguishing features of MOGAD including lack of female predominance, higher incidence of acute disseminated encephalomyelitis (ADEM), higher proportion of bilateral optic neurit...
Introduction null Myelin oligodendrocyte glycoprotein antibodies (MOG-abs) are associated with demyelinating diseases. Leptomeningeal enhancement occurs in 6% of adult MOG-abs patients but rates in pediatric MOG-abs patients are unknown. null Methods null Retrospective review of pediatric MOG-abs patients was performed. null Results null Twenty-one patients (7 boys, 14 girls) were included with an average age of 8.6 years (range 2-15 years). Seven of 21 (33%) pediatric MOG-abs patients had lepto...
Cell-based therapies are gaining momentum as promising treatments for rare neurological autoimmune diseases, including neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody-associated disease. The development of targeted cell therapies is hampered by the lack of adequate animal models that mirror the human disease. Most cell-based treatments, including HSCT, CAR-T cell, tolerogenic dendritic cell and mesenchymal stem cell treatment have entered early stage clin...
#1Tiziana Carandini(Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico)H-Index: 8
#2Luca Sacchi(Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico)
Last. Anna M. Pietroboni(Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico)H-Index: 15
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Abstract null null Background null : the distinct MRI features of MOG-antibody disease (MOG-AD) and AQP4-NMOSD are still poorly defined. We performed a systematic review and meta-analysis to identify specific patterns of MRI abnormalities able to discriminate between MOG-AD and AQP4-NMOSD. null null null Methods null : fourteen case-series (1028 patients) were included. Outcomes were MRI lesion patterns in optic nerve (ON), brain and spinal cord (SC) that were selected after a systematic literat...
To emphasize physio-pathological, clinical and prognosis differences between conditions causing serious and sometimes very similar clinical manifestations: anti-aquaporin-4 (AQP4) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies related diseases, and seronegative NMOSD (neuromyelitis optica spectrum disorders). Based on Wingerchuk et al. (Neurology 85:177-189, 2015) criteria for NMOSD and on those more recently proposed by Jarius et al. (J Neuroinflammation 15:134, 2018) for MOGAD (...
AIMS Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) have been proposed to define "MOG encephalomyelitis" (MOG-EM), with published diagnostic and "red flag" criteria. We aimed to evaluate these criteria in a routine clinical setting. METHODS We retrospectively analyzed patients with borderline/positive MOG-IgG and applied the diagnostic and red flag criteria to determine likelihood of MOG-EM diagnosis. Para-/clinical parameters were described and analyzed with chi-square test. RESULTS I...
Background Neurological disorders with IgG antibodies against myelin-oligodendrocyte glycoprotein (MOG-IgG) have been increasingly recognised as a new type of neuroinflammatory disorder. Objective The study aimed to identify regional and ethnic differences in clinical profiles of MOG-IgG–associated disorders between East Asian (Japanese) and Caucasian (German) patients. Methods Demographic, clinical and therapeutic data from 68 MOG-IgG–positive adults were collected (Japanese, n=44; German, n=24...
Last. Achim Berthele(TUM: Technische Universität München)H-Index: 48
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Introduction Neuromyelitis optica spectrum disorders (NMOSD) are rare neuroinflammatory demyelinating diseases of the CNS, mainly affecting optic nerves, spinal cord and brainstem regions. The diagnosis depends on clinical symptoms, MRI findings and the detection of autoantibodies against the water channel aquaporin 4 (AQP4-Ab). This autoantibody is particularly important for diagnostic sensitivity and specificity and further sets the course for major therapeutic decisions. Due to a relapsing co...
Neuromyelitis optica spectrum disorder (NMOSD) is a rare and debilitating autoimmune astrocytopathy with a predominantly relapsing disease course. Satralizumab, a humanized monoclonal antibody, was designed to treat NMOSD by targeting the IL-6 receptor. Satralizumab builds on positive experiences of off-label use tocilizumab in recent years. Before 2019, no medications were approved for the treatment of NMOSD. In 2020, satralizumab became the third compound to enter the US market, adding to the ...
#1Jonas Graf(UCSF: University of California, San Francisco)H-Index: 8
#2Jan Mares(UCSF: University of California, San Francisco)H-Index: 12
Last. Hans-Peter Hartung(UCSF: University of California, San Francisco)H-Index: 2
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Ocrelizumab, rituximab, ofatumumab, ublituximab, inebilizumab, and evobrutinib are immunotherapies that target various B cell–related proteins. Most of these treatments have proven efficacy in relapsing and progressive forms of MS and neuromyelitis optica spectrum disease (NMOSD), or are in advanced stages of clinical development. Currently, ocrelizumab, ofatumumab, and inebilizumab are licensed for treatment of MS and NMOSD, respectively. This review focuses on the current state of knowledge ab...
