PMID- 32412053 OWN - NLM STAT- MEDLINE DCOM- 20201214 LR - 20201214 IS - 1460-2156 (Electronic) IS - 0006-8950 (Linking) VI - 143 IP - 5 DP - 2020 May 1 TI - Myelin oligodendrocyte glycoprotein antibody-associated disease: an immunopathological study. PG - 1431-1446 LID - 10.1093/brain/awaa102 [doi] AB - Conformation-sensitive antibodies against myelin oligodendrocyte glycoprotein (MOG) are detectable in patients with optic neuritis, myelitis, opticomyelitis, acute or multiphasic disseminated encephalomyelitis (ADEM/MDEM) and brainstem/cerebral cortical encephalitis, but are rarely detected in patients with prototypic multiple sclerosis. So far, there has been no systematic study on the pathological relationship between demyelinating lesions and cellular/humoral immunity in MOG antibody-associated disease. Furthermore, it is unclear whether the pathomechanisms of MOG antibody-mediated demyelination are similar to the demyelination patterns of multiple sclerosis, neuromyelitis optica spectrum disorders (NMOSD) with AQP4 antibody, or ADEM. In this study, we immunohistochemically analysed biopsied brain tissues from 11 patients with MOG antibody-associated disease and other inflammatory demyelinating diseases. Patient median onset age was 29 years (range 9-64), and the median interval from attack to biopsy was 1 month (range 0.5-96). The clinical diagnoses were ADEM (n = 2), MDEM (n = 1), multiple brain lesions without encephalopathy (n = 3), leukoencephalopathy (n = 3) and cortical encephalitis (n = 2). All these cases had multiple/extensive lesions on MRI and were oligoclonal IgG band-negative. Most demyelinating lesions in 10 of 11 cases showed a perivenous demyelinating pattern previously reported in ADEM (153/167 lesions) and a fusion pattern (11/167 lesions) mainly in the cortico-medullary junctions and white matter, and only three lesions in two cases showed confluent demyelinated plaques. In addition, 60 of 167 demyelinating lesions (mainly in the early phase) showed MOG-dominant myelin loss, but relatively preserved oligodendrocytes, which were distinct from those of AQP4 antibody-positive NMOSD exhibiting myelin-associated glycoprotein-dominant oligodendrogliopathy. In MOG antibody-associated diseases, MOG-laden macrophages were found in the perivascular spaces and demyelinating lesions, and infiltrated cells were abundant surrounding multiple blood vessels in and around the demyelinating lesions, mainly consisting of macrophages (CD68; 1814 +/- 1188 cells/mm2), B cells (CD20; 468 +/- 817 cells/mm2), and T cells (CD3; 2286 +/- 1951 cells/mm2), with CD4-dominance (CD4+ versus CD8+; 1281 +/- 1196 cells/mm2 versus 851 +/- 762 cells/mm2, P < 0.01). Humoral immunity, evidenced by perivascular deposits of activated complements and immunoglobulins, was occasionally observed in some MOG antibody-associated demyelinating lesions, and the frequency was much lower than that in AQP4 antibody-positive NMOSD. Subpial lesions with perivenous demyelination were observed in both ADEM and cortical encephalitis. Our study suggests that ADEM-like perivenous inflammatory demyelination with MOG-dominant myelin loss is a characteristic finding of MOG antibody-associated disease regardless of whether the diagnostic criteria of ADEM are met. These pathological features are clearly different from those of multiple sclerosis and AQP4 antibody-positive NMOSD, suggesting an independent autoimmune demyelinating disease entity. CI - (c) The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Takai, Yoshiki AU - Takai Y AD - Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. FAU - Misu, Tatsuro AU - Misu T AD - Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. AD - Department of Multiple Sclerosis Therapeutics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. FAU - Kaneko, Kimihiko AU - Kaneko K AD - Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. AD - Department of Neurology, National Hospital Organization Miyagi National Hospital, Watari, Miyagi, Japan. FAU - Chihara, Norio AU - Chihara N AD - Division of Neurology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan. FAU - Narikawa, Koichi AU - Narikawa K AD - Department of Neurology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Miyagi, Japan. FAU - Tsuchida, Satoko AU - Tsuchida S AD - Department of Pediatrics, Japanese Red Cross Akita Hospital, Akita, Akita, Japan. FAU - Nishida, Hiroya AU - Nishida H AD - Department of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, Fuchu, Tokyo, Japan. FAU - Komori, Takashi AU - Komori T AD - Department of Laboratory Medicine and Pathology, Tokyo Metropolitan Neurological Hospital, Fuchu, Tokyo, Japan. FAU - Seki, Morinobu AU - Seki M AD - Department of Neurology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan. FAU - Komatsu, Teppei AU - Komatsu T AD - Department of Neurology, the Jikei University School of Medicine, Minato-ku, Tokyo, Japan. FAU - Nakamagoe, Kiyotaka AU - Nakamagoe K AD - Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. FAU - Ikeda, Toshimasa AU - Ikeda T AD - Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Aichi, Japan. FAU - Yoshida, Mari AU - Yoshida M AD - Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Aichi, Japan. FAU - Takahashi, Toshiyuki AU - Takahashi T AD - Department of Neurology, National Hospital Organization Yonezawa National Hospital, Yonezawa, Yamagata, Japan. FAU - Ono, Hirohiko AU - Ono H AD - Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. FAU - Nishiyama, Shuhei AU - Nishiyama S AD - Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. FAU - Kuroda, Hiroshi AU - Kuroda H AD - Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. FAU - Nakashima, Ichiro AU - Nakashima I AD - Department of Neurology, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan. FAU - Suzuki, Hiroyoshi AU - Suzuki H AD - Department of Pathology, National Hospital Organization Sendai Medical Center, Sendai, Miyagi, Japan. FAU - Bradl, Monika AU - Bradl M AD - Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Vienna, Austria. FAU - Lassmann, Hans AU - Lassmann H AD - Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Vienna, Austria. FAU - Fujihara, Kazuo AU - Fujihara K AD - Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. AD - Department of Multiple Sclerosis Therapeutics, Fukushima Medical University, Fukushima, Fukushima, Japan. FAU - Aoki, Masashi AU - Aoki M AD - Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. CN - Japan MOG-antibody Disease Consortium LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Brain JT - Brain : a journal of neurology JID - 0372537 RN - 0 (Autoantibodies) RN - 0 (Autoantigens) RN - 0 (MOG protein, human) RN - 0 (Myelin-Oligodendrocyte Glycoprotein) SB - IM MH - Adolescent MH - Adult MH - Autoantibodies/immunology MH - Autoantigens/immunology MH - Brain/*pathology MH - Child MH - Demyelinating Autoimmune Diseases, CNS/*immunology/*pathology MH - Female MH - Humans MH - Male MH - Middle Aged MH - Myelin-Oligodendrocyte Glycoprotein/*immunology MH - Young Adult OTO - NOTNLM OT - acute disseminated encephalomyelitis OT - antibody OT - myelin oligodendrocyte glycoprotein OT - pattern-II multiple sclerosis OT - perivenous demyelination FIR - Otsuka, Yoshihisa IR - Otsuka Y FIR - Nishimaki, Keiichi IR - Nishimaki K FIR - Ishigaki, Sho IR - Ishigaki S FIR - Yoshida, Kazunari IR - Yoshida K FIR - Iguchi, Yasuyuki IR - Iguchi Y FIR - Fukuda, Takahiro IR - Fukuda T FIR - Nohara, Seitaro IR - Nohara S FIR - Tamaoka, Akira IR - Tamaoka A FIR - Fujimori, Juichi IR - Fujimori J EDAT- 2020/05/16 06:00 MHDA- 2020/12/15 06:00 CRDT- 2020/05/16 06:00 PHST- 2019/02/22 00:00 [received] PHST- 2019/07/31 00:00 [revised] PHST- 2020/02/17 00:00 [accepted] PHST- 2020/05/16 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2020/05/16 06:00 [entrez] AID - 5837518 [pii] AID - 10.1093/brain/awaa102 [doi] PST - ppublish SO - Brain. 2020 May 1;143(5):1431-1446. doi: 10.1093/brain/awaa102.