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Interestingly, pediatric MOGAD is not more aggressive than adult-onset MOGAD, unlike in multiple sclerosis (MS), where annualized relapse rates are three times higher in pediatric-onset MS. MOGAD pathophysiology is driven by acute attacks during which T cells and MOG antibodies cross blood brain barrier (BBB). MOGAD lesions show a perivenous confluent pattern around the small veins, lacking the radiological central vein sign. Initial activation of T cells in the periphery is followed by reactivation in the subarachnoid\/perivascular spaces by MOG-laden antigen-presenting cells and inflammatory CSF milieu, which enables T cells to infiltrate CNS parenchyma. CD4+ T cells, unlike CD8+ T cells in MS, are the dominant T cell type found in lesion histology. Granulocytes, macrophages\/microglia, and activated complement are also found in the lesions, which could contribute to demyelination during acute relapses. MOG antibodies potentially contribute to pathology by opsonizing MOG, complement activation, and antibody-dependent cellular cytotoxicity. Stimulation of peripheral MOG-specific B cells through TLR stimulation or T follicular helper cells might help differentiate MOG antibody-producing plasma cells in the peripheral blood. Neuroinflammatory biomarkers (such as MBP, sNFL, GFAP, Tau) in MOGAD support that most axonal damage happens in the initial attack, whereas relapses are associated with increased myelin damage.<\/jats:p>","DOI":"10.3389\/fneur.2023.1137998","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T11:53:13Z","timestamp":1678103593000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":108,"title":["Pathophysiology of myelin oligodendrocyte glycoprotein antibody disease"],"prefix":"10.3389","volume":"14","author":[{"given":"Osman","family":"Corbali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanuja","family":"Chitnis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"529","DOI":"10.3389\/fimmu.2017.00529","article-title":"Myelin oligodendrocyte glycoprotein: deciphering a target in inflammatory demyelinating diseases","volume":"8","author":"Peschl","year":"2017","journal-title":"Front Immunol."},{"key":"B2","unstructured":"Differential ultrastructural localization of myelin basic protein, myelin\/oligodendroglial glycoprotein, and 2',3'-cyclic nucleotide 3'-phosphodiesterase in the CNS of adult rats296304\n            BrunnerC\n            LassmannH\n            WaehneldtTV\n            MatthieuJM\n            LiningtonC\n          10.1111\/j.1471-4159.1989.tb10930.x2462020J Neurochem521989"},{"key":"B3","doi-asserted-by":"publisher","first-page":"8985","DOI":"10.1074\/jbc.M413174200","article-title":"Signaling cascades activated upon antibody cross-linking of myelin oligodendrocyte glycoprotein: potential implications for multiple sclerosis","volume":"280","author":"Marta","year":"2005","journal-title":"J Biol Chem."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1046\/j.1471-4159.1999.0720001.x","article-title":"The structure and function of myelin oligodendrocyte glycoprotein","volume":"72","author":"Johns","year":"1999","journal-title":"J Neurochem"},{"key":"B5","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1016\/S1474-4422(21)00218-0","article-title":"Myelin-oligodendrocyte glycoprotein antibody-associated disease","volume":"20","author":"Marignier","year":"2021","journal-title":"Lancet Neurol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/1742-2094-9-14","article-title":"Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients","volume":"9","author":"Jarius","year":"2012","journal-title":"J Neuroinflamm."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e007766","DOI":"10.1136\/bmjopen-2015-007766","article-title":"Antibodies to myelin oligodendrocyte glycoprotein in idiopathic optic neuritis","volume":"5","author":"Nakajima","year":"2015","journal-title":"BMJ Open."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e40","DOI":"10.1212\/NXI.0000000000000040","article-title":"Antibodies to myelin oligodendrocyte glycoprotein in bilateral and recurrent optic neuritis","volume":"1","author":"Ramanathan","year":"2014","journal-title":"Neurol Neuroimmunol Neuroinflamm."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1001\/jamaneurol.2018.1814","article-title":"Association of MOG-IgG serostatus with relapse after acute disseminated encephalomyelitis and proposed diagnostic criteria for MOG-IgG-associated disorders","volume":"75","author":"L\u00f3pez-Chiriboga","year":"2018","journal-title":"JAMA Neurol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1186\/s12974-016-0718-0","article-title":"MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. 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