{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:17:09Z","timestamp":1792793829978,"version":"4.5.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"KAKENHI","award":["#17K16108"],"award-info":[{"award-number":["#17K16108"]}]},{"name":"KAKENHI","award":["#17H04192"],"award-info":[{"award-number":["#17H04192"]}]},{"name":"KAKENHI","award":["#15K09332"],"award-info":[{"award-number":["#15K09332"]}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Japan and the Grants-in-Aid for Scientific Research"},{"name":"Ministry of Health, Labour and Welfare of Japan","id":[{"id":"https:\/\/ror.org\/03mwa7s65","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Conformation-sensitive antibodies against myelin oligodendrocyte glycoprotein (MOG) are detectable in patients with optic neuritis, myelitis, opticomyelitis, acute or multiphasic disseminated encephalomyelitis (ADEM\/MDEM) and brainstem\/cerebral cortical encephalitis, but are rarely detected in patients with prototypic multiple sclerosis. So far, there has been no systematic study on the pathological relationship between demyelinating lesions and cellular\/humoral immunity in MOG antibody-associated disease. Furthermore, it is unclear whether the pathomechanisms of MOG antibody-mediated demyelination are similar to the demyelination patterns of multiple sclerosis, neuromyelitis optica spectrum disorders (NMOSD) with AQP4 antibody, or ADEM. In this study, we immunohistochemically analysed biopsied brain tissues from 11 patients with MOG antibody-associated disease and other inflammatory demyelinating diseases. Patient median onset age was 29 years (range 9\u201364), and the median interval from attack to biopsy was 1 month (range 0.5\u201396). The clinical diagnoses were ADEM (n\u2009=\u20092), MDEM (n\u2009=\u20091), multiple brain lesions without encephalopathy (n\u2009=\u20093), leukoencephalopathy (n\u2009=\u20093) and cortical encephalitis (n\u2009=\u20092). All these cases had multiple\/extensive lesions on MRI and were oligoclonal IgG band-negative. Most demyelinating lesions in 10 of 11 cases showed a perivenous demyelinating pattern previously reported in ADEM (153\/167 lesions) and a fusion pattern (11\/167 lesions) mainly in the cortico-medullary junctions and white matter, and only three lesions in two cases showed confluent demyelinated plaques. In addition, 60 of 167 demyelinating lesions (mainly in the early phase) showed MOG-dominant myelin loss, but relatively preserved oligodendrocytes, which were distinct from those of AQP4 antibody-positive NMOSD exhibiting myelin-associated glycoprotein-dominant oligodendrogliopathy. In MOG antibody-associated diseases, MOG-laden macrophages were found in the perivascular spaces and demyelinating lesions, and infiltrated cells were abundant surrounding multiple blood vessels in and around the demyelinating lesions, mainly consisting of macrophages (CD68; 1814\u2009\u00b1\u20091188 cells\/mm2), B cells (CD20; 468\u2009\u00b1\u2009817 cells\/mm2), and T cells (CD3; 2286\u2009\u00b1\u20091951 cells\/mm2), with CD4-dominance (CD4+ versus CD8+; 1281\u2009\u00b1\u20091196 cells\/mm2 versus 851\u2009\u00b1\u2009762 cells\/mm2, P\u2009&amp;lt;\u20090.01). Humoral immunity, evidenced by perivascular deposits of activated complements and immunoglobulins, was occasionally observed in some MOG antibody-associated demyelinating lesions, and the frequency was much lower than that in AQP4 antibody-positive NMOSD. Subpial lesions with perivenous demyelination were observed in both ADEM and cortical encephalitis. Our study suggests that ADEM-like perivenous inflammatory demyelination with MOG-dominant myelin loss is a characteristic finding of MOG antibody-associated disease regardless of whether the diagnostic criteria of ADEM are met. These pathological features are clearly different from those of multiple sclerosis and AQP4 antibody-positive NMOSD, suggesting an independent autoimmune demyelinating disease entity.<\/jats:p>","DOI":"10.1093\/brain\/awaa102","type":"journal-article","created":{"date-parts":[[2020,3,15]],"date-time":"2020-03-15T08:29:20Z","timestamp":1584260960000},"page":"1431-1446","source":"Crossref","is-referenced-by-count":287,"title":["Myelin oligodendrocyte glycoprotein antibody-associated disease: an immunopathological study"],"prefix":"10.1093","volume":"143","author":[{"given":"Yoshiki","family":"Takai","sequence":"first","affiliation":[{"name":"Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Misu","sequence":"first","affiliation":[{"name":"Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"},{"name":"Department of Multiple Sclerosis Therapeutics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimihiko","family":"Kaneko","sequence":"first","affiliation":[{"name":"Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"},{"name":"Department of Neurology, National Hospital Organization Miyagi National Hospital, Watari, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Chihara","sequence":"first","affiliation":[{"name":"Division of Neurology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Narikawa","sequence":"first","affiliation":[{"name":"Department of Neurology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Tsuchida","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Japanese Red Cross Akita Hospital, Akita, Akita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroya","family":"Nishida","sequence":"first","affiliation":[{"name":"Department of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, Fuchu, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Komori","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Tokyo Metropolitan Neurological Hospital, Fuchu, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morinobu","family":"Seki","sequence":"first","affiliation":[{"name":"Department of Neurology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teppei","family":"Komatsu","sequence":"first","affiliation":[{"name":"Department of Neurology, the Jikei University School of Medicine, Minato-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyotaka","family":"Nakamagoe","sequence":"first","affiliation":[{"name":"Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshimasa","family":"Ikeda","sequence":"first","affiliation":[{"name":"Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Yoshida","sequence":"first","affiliation":[{"name":"Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Takahashi","sequence":"first","affiliation":[{"name":"Department of Neurology, National Hospital Organization Yonezawa National Hospital, Yonezawa, Yamagata, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohiko","family":"Ono","sequence":"first","affiliation":[{"name":"Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Nishiyama","sequence":"first","affiliation":[{"name":"Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kuroda","sequence":"first","affiliation":[{"name":"Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Nakashima","sequence":"first","affiliation":[{"name":"Department of Neurology, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyoshi","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Pathology, National Hospital Organization Sendai Medical Center, Sendai, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Bradl","sequence":"first","affiliation":[{"name":"Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Lassmann","sequence":"first","affiliation":[{"name":"Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Fujihara","sequence":"first","affiliation":[{"name":"Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"},{"name":"Department of Multiple Sclerosis Therapeutics, Fukushima Medical University, Fukushima, Fukushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Aoki","sequence":"first","affiliation":[{"name":"Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Japan MOG-antibody Disease Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihisa","family":"Otsuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Nishimaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Ishigaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunari","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Iguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seitaro","family":"Nohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Tamaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juichi","family":"Fujimori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,15]]},"reference":[{"key":"2020052115184321400_awaa102-B1","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.it.2011.03.008","article-title":"Interferon-beta 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