The Potential Pathogenicity of Myelin Oligodendrocyte Glycoprotein Antibodies in the Optic Pathway.
Journal
Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society
ISSN: 1536-5166
Titre abrégé: J Neuroophthalmol
Pays: United States
ID NLM: 9431308
Informations de publication
Date de publication:
01 03 2023
01 03 2023
Historique:
pubmed:
3
2
2023
medline:
17
2
2023
entrez:
2
2
2023
Statut:
ppublish
Résumé
Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an acquired inflammatory demyelinating disease with optic neuritis (ON) as the most frequent clinical symptom. The hallmark of the disease is the presence of autoantibodies against MOG (MOG-IgG) in the serum of patients. Whereas the role of MOG in the experimental autoimmune encephalomyelitis animal model is well-established, the pathogenesis of the human disease and the role of human MOG-IgG is still not fully clear. PubMed was searched for the terms "MOGAD," "optic neuritis," "MOG antibodies," and "experimental autoimmune encephalomyelitis" alone or in combination, to find articles of interest for this review. Only articles written in English language were included and reference lists were searched for further relevant papers. B and T cells play a role in the pathogenesis of human MOGAD. The distribution of lesions and their development toward the optic pathway is influenced by the genetic background in animal models. Moreover, MOGAD-associated ON is frequently bilateral and often relapsing with generally favorable visual outcome. Activated T-cell subsets create an inflammatory environment and B cells are necessary to produce autoantibodies directed against the MOG protein. Here, pathologic mechanisms of MOG-IgG are discussed, and histopathologic findings are presented. MOGAD patients often present with ON and harbor antibodies against MOG. Furthermore, pathogenesis is most likely a synergy between encephalitogenic T and antibody producing B cells. However, to which extent MOG-IgG are pathogenic and the exact pathologic mechanism is still not well understood.
Sections du résumé
BACKGROUND
Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an acquired inflammatory demyelinating disease with optic neuritis (ON) as the most frequent clinical symptom. The hallmark of the disease is the presence of autoantibodies against MOG (MOG-IgG) in the serum of patients. Whereas the role of MOG in the experimental autoimmune encephalomyelitis animal model is well-established, the pathogenesis of the human disease and the role of human MOG-IgG is still not fully clear.
EVIDENCE ACQUISITION
PubMed was searched for the terms "MOGAD," "optic neuritis," "MOG antibodies," and "experimental autoimmune encephalomyelitis" alone or in combination, to find articles of interest for this review. Only articles written in English language were included and reference lists were searched for further relevant papers.
RESULTS
B and T cells play a role in the pathogenesis of human MOGAD. The distribution of lesions and their development toward the optic pathway is influenced by the genetic background in animal models. Moreover, MOGAD-associated ON is frequently bilateral and often relapsing with generally favorable visual outcome. Activated T-cell subsets create an inflammatory environment and B cells are necessary to produce autoantibodies directed against the MOG protein. Here, pathologic mechanisms of MOG-IgG are discussed, and histopathologic findings are presented.
CONCLUSIONS
MOGAD patients often present with ON and harbor antibodies against MOG. Furthermore, pathogenesis is most likely a synergy between encephalitogenic T and antibody producing B cells. However, to which extent MOG-IgG are pathogenic and the exact pathologic mechanism is still not well understood.
Identifiants
pubmed: 36729854
doi: 10.1097/WNO.0000000000001772
pii: 00041327-202303000-00002
pmc: PMC9924971
doi:
Substances chimiques
Myelin-Oligodendrocyte Glycoprotein
0
Autoantibodies
0
Immunoglobulin G
0
Types de publication
Review
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5-16Subventions
Organisme : Austrian Science Fund FWF
ID : P 32699
Pays : Austria
Informations de copyright
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the North American Neuro-Opthalmology Society.
Déclaration de conflit d'intérêts
A. Bauer has participated in meetings sponsored by or received travel funding from Novartis, Sanofi-Genzyme, Merck, Almirall and Biogen. M. Reindl was supported by research support from Euroimmun and Roche (to institution). The University Hospital and Medical University of Innsbruck (Austria, employer of M. Reindl) receives payments for antibody assays (MOG, AQP4, and other autoantibodies) and for MOG and AQP4 antibody validation experiments organized by Euroimmun (Lübeck, Germany). M. Lerch has no conflict of interest to declare.
Références
Peschl P, Bradl M, Höftberger R, Berger T, Reindl M. Myelin oligodendrocyte glycoprotein: deciphering a target in inflammatory demyelinating diseases. Front Immunol. 2017;8:529.
Clements CS, Reid HH, Beddoe T, Tynan FE, Perugini MA, Johns TG, Bernard CCA, Rossjohn J. The crystal structure of myelin oligodendrocyte glycoprotein, a key autoantigen in multiple sclerosis. Proc Natl Acad Sci U S A. 2003;100:11059–11064.
Birling MC, Roussel G, Nussbaum F, Nussbaum JL. Biochemical and immunohistochemical studies with specific polyclonal antibodies directed against bovine myelin/oligodendrocyte glycoprotein. Neurochem Res. 1993;18:937–945.
Delarasse C, Della Gaspera B, Lu CW, Lachapelle F, Gelot A, Rodriguez D, Dautigny A, Genain C, Pham-Dinh D. Complex alternative splicing of the myelin oligodendrocyte glycoprotein gene is unique to human and non-human primates. J Neurochem. 2006;98:1707–1717.
Johns TG, Bernard CC. The structure and function of myelin oligodendrocyte glycoprotein. J Neurochem. 1999;72:1–9.
Dyer CA, Matthieu JM. Antibodies to myelin/oligodendrocyte-specific protein and myelin/oligodendrocyte glycoprotein signal distinct changes in the organization of cultured oligodendroglial membrane sheets. J Neurochem. 1994;62:777–787.
Johns TG, Bernard CCA. Binding of complement component Clq to myelin oligodendrocyte glycoprotein: a novel mechanism for regulating CNS inflammation. Mol Immunol. 1997;34:33–38.
von Büdingen HC, Mei F, Greenfield A, Jahn S, Shen Y-AA, Reid HH, McKemy DD, Chan JR. The myelin oligodendrocyte glycoprotein directly binds nerve growth factor to modulate central axon circuitry. J Cell Biol. 2015;210:891–898.
García-Vallejo JJ, Ilarregui JM, Kalay H, Chamorro S, Koning N, Unger WW, Ambrosini M, Montserrat V, Fernandes RJ, Bruijns SCM, van Weering JRT, Paauw NJ, O'Toole T, van Horssen J, van der Valk P, Nazmi K, Bolscher JGM, Bajramovic J, Dijkstra CD, 't Hart BA, van Kooyk Y. CNS myelin induces regulatory functions of DC-SIGN-expressing, antigen-presenting cells via cognate interaction with MOG. J Exp Med. 2014;211:1465–1483.
Cong H, Jiang Y, Tien P. Identification of the myelin oligodendrocyte glycoprotein as a cellular receptor for rubella virus. J Virol. 2011;85:11038–11047.
Reindl M, Waters P. Myelin oligodendrocyte glycoprotein antibodies in neurological disease. Nat Rev Neurol. 2019;15:89–102.
de Mol CL, Wong Y, van Pelt ED, Wokke B, Siepman T, Neuteboom RF, Hamann D, Hintzen RQ. The clinical spectrum and incidence of anti-MOG-associated acquired demyelinating syndromes in children and adults. Mult Scler. 2020;26:806–814.
Bartels F, Lu A, Oertel FC, Finke C, Paul F, Chien C. Clinical and neuroimaging findings in MOGAD-MRI and OCT. Clin Exp Immunol. 2021;206:266–281.
Brill L, Ganelin-Cohen E, Dabby R, Rabinowicz S, Zohar-Dayan E, Rein N, Aloni E, Karmon Y, Vaknin-Dembinsky A. Age-related clinical presentation of MOG-IgG seropositivity in Israel. Front Neurol. 2020;11:612304.
Jurynczyk M, Messina S, Woodhall MR, Raza N, Everett R, Roca-Fernandez A, Tackley G, Hamid S, Sheard A, Reynolds G, Chandratre S, Hemingway C, Jacob A, Vincent A, Leite MI, Waters P, Palace J. Clinical presentation and prognosis in MOG-antibody disease: a UK study. Brain. 2017;140:3128–3138.
Cobo-Calvo A, Ruiz A, Maillart E, Audoin B, Zephir H, Bourre B, Ciron J, Collongues N, Brassat D, Cotton F, Papeix C, Durand-Dubief F, Laplaud D, Deschamps R, Cohen M, Biotti D, Ayrignac X, Tilikete C, Thouvenot E, Brochet B, Dulau C, Moreau T, Tourbah A, Lebranchu P, Michel L, Lebrun-Frenay C, Montcuquet A, Mathey G, Debouverie M, Pelletier J, Labauge P, Derache N, Coustans M, Rollot F, De Seze J, Vukusic S, Marignier R; OFSEP and NOMADMUS Study Group. Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: the MOGADOR study. Neurology. 2018;90:e1858–e1869.
Armangue T, Olivé-Cirera G, Martínez-Hernandez E, Sepulveda M, Ruiz-Garcia R, Muñoz-Batista M, Ariño H, González-Álvarez V, Felipe-Rucián A, Jesús Martínez-González M, Cantarín-Extremera V, Concepción Miranda-Herrero M, Monge-Galindo L, Tomás-Vila M, Miravet E, Málaga I, Arrambide G, Auger C, Tintoré M, Montalban X, Vanderver A, Graus F, Saiz A, Dalmau J, Spanish Pediatric anti-MOG Study Group, Aguilera-Albesa S, Alvarez Demanuel D, Alvarez Molinero M, Aquino Fariña L, Arrabal L, Arriola-Pereda G, Aznar-Laín G, Benavides-Medina M, Bermejo T, Blanco-Lago R, Caballero E, Calvo R, Camacho Salas A, Conejo-Moreno D, Delgadillo-Chilavert V, Elosegi-Castellanos A, Esteban Canto V, Fernández-Ramos J, Garcia-Puig M, García-Ribes A, Gómez-Martín H, Gonzalez-Barrios D, González-Gutiérrez-Solana L, Jimena-Garcia S, Jiménez-Legido M, Juliá-Palacios N, López-Laso E, Martí-Carrera I, Martínez González M, Martín-Viota L, Mattozi S, Maqueda-Castellote E, Mendibe MDM, Mora-Ramírez MD, Muñoz-Cabello B, Navarro-Morón J, Nunes-Cabrera T, Orellana G, Pujol-Soler B, Querol L, Ramírez A, Rodriguez-Lucenilla MI, Ruiz C, Soto-Insuga V, Toledo Bravo de Laguna L, Turon-Viñas E, Vázquez-López M, Villar-Vera C. Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: a multicentre observational study. Lancet Neurol. 2020;19:234–246.
Waters P, Fadda G, Woodhall M, O'Mahony J, Brown RA, Castro DA, Longoni G, Irani SR, Sun B, Yeh EA, Marrie RA, Arnold DL, Banwell B, Bar-Or A; Canadian Pediatric Demyelinating Disease Network. Serial anti-myelin oligodendrocyte glycoprotein antibody analyses and outcomes in children with demyelinating syndromes. JAMA Neurol. 2020;77:82–93.
de Mol CL, Wong YYM, van Pelt ED, Ketelslegers IA, Bakker DP, Boon M, Braun KPJ, van Dijk KGJ, Eikelenboom MJ, Engelen M, Geleijns K, Haaxma CA, Niermeijer JMF, Niks EH, Peeters EAJ, Peeters-Scholte CMPCD, Poll-The BT, Portier RP, de Rijk-van Andel JF, Samijn JPA, Schippers HM, Snoeck IN, Stroink H, Vermeulen RJ, Verrips A, Visscher F, Vles JSH, Willemsen MAAP, Catsman-Berrevoets CE, Hintzen RQ, Neuteboom RF. Incidence and outcome of acquired demyelinating syndromes in Dutch children: update of a nationwide and prospective study. J Neurol. 2018;265:1310–1319.
Senanayake B, Jitprapaikulsan J, Aravinthan M, Wijesekera JC, Ranawaka UK, Riffsy MT, Paramanathan T, Sagen J, Fryer JP, Schmeling J, Majed M, Flanagan EP, Pittock SJ. Seroprevalence and clinical phenotype of MOG-IgG-associated disorders in Sri Lanka. J Neurol Neurosurg Psychiatry. 2019;90:1381–1383.
Rossor T, Benetou C, Wright S, Duignan S, Lascelles K, Robinson R, Das K, Ciccarelli O, Wassmer E, Hemingway C, Lim M, Hacohen Y. Early predictors of epilepsy and subsequent relapse in children with acute disseminated encephalomyelitis. Mult Scler. 2020;26:333–342.
Hennes E-M, Baumann M, Schanda K, Anlar B, Bajer-Kornek B, Blaschek A, Brantner-Inthaler S, Diepold K, Eisenkölbl A, Gotwald T, Kuchukhidze G, Gruber-Sedlmayr U, Häusler M, Höftberger R, Karenfort M, Klein A, Koch J, Kraus V, Lechner C, Leiz S, Leypoldt F, Mader S, Marquard K, Poggenburg I, Pohl D, Pritsch M, Raucherzauner M, Schimmel M, Thiels C, Tibussek D, Vieker S, Zeches C, Berger T, Reindl M, Rostásy K; BIOMARKER Study Group. Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome. Neurology. 2017;89:900–908.
O'Connor KC, McLaughlin KA, De Jager PL, Chitnis T, Bettelli E, Xu C, Robinson WH, Cherry SV, Bar-Or A, Banwell B, Fukaura H, Fukazawa T, Tenembaum S, Wong SJ, Tavakoli NP, Idrissova Z, Viglietta V, Rostasy K, Pohl D, Dale RC, Freedman M, Steinman L, Buckle GJ, Kuchroo VK, Hafler DA, Wucherpfennig KW. Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein. Nat Med. 2007;13:211–217.
Brehm U, Piddlesden SJ, Gardinier MV, Linington C. Epitope specificity of demyelinating monoclonal autoantibodies directed against the human myelin oligodendrocyte glycoprotein (MOG). J Neuroimmunol. 1999;97:9–15.
Menge T, Lalive PH, von Büdingen HC, Genain CP. Conformational epitopes of myelin oligodendrocyte glycoprotein are targets of potentially pathogenic antibody responses in multiple sclerosis. J Neuroinflammation. 2011;8:161.
Mayer MC, Breithaupt C, Reindl M, Schanda K, Rostásy K, Berger T, Dale RC, Brilot F, Olsson T, Jenne D, Pröbstel A-K, Dornmair K, Wekerle H, Hohlfeld R, Banwell B, Bar-Or A, Meinl E. Distinction and temporal stability of conformational epitopes on myelin oligodendrocyte glycoprotein recognized by patients with different inflammatory central nervous system diseases. J Immunol. 2013;191:3594–3604.
Tea F, Lopez JA, Ramanathan S, Merheb V, Lee FXZ, Zou A, Pilli D, Patrick E, van der Walt A, Monif M, Tantsis EM, Yiu EM, Vucic S, Henderson APD, Fok A, Fraser CL, Lechner-Scott J, Reddel SW, Broadley S, Barnett MH, Brown DA, Lunemann JD, Dale RC, Brilot F; Australasian and New Zealand MOG Study Group. Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination. Acta Neuropathol Commun. 2019;7:145.
Breithaupt C, Schäfer B, Pellkofer H, Huber R, Linington C, Jacob U. Demyelinating myelin oligodendrocyte glycoprotein-specific autoantibody response is focused on one dominant conformational epitope region in rodents. J Immunol. 2008;181:1255–1263.
Peschl P, Schanda K, Zeka B, Given K, Böhm D, Ruprecht K, Saiz A, Lutterotti A, Rostásy K, Höftberger R, Berger T, Macklin W, Lassmann H, Bradl M, Bennett JL, Reindl M. Human antibodies against the myelin oligodendrocyte glycoprotein can cause complement-dependent demyelination. J Neuroinflammation. 2017;14:208.
Sepúlveda M, Armangue T, Martinez-Hernandez E, Arrambide G, Sola-Valls N, Sabater L, Téllez N, Midaglia L, Ariño H, Peschl P, Reindl M, Rovira A, Montalban X, Blanco Y, Dalmau J, Graus F, Saiz A. Clinical spectrum associated with MOG autoimmunity in adults: significance of sharing rodent MOG epitopes. J Neurol. 2016;263:1349–1360.
Spadaro M, Gerdes LA, Mayer MC, Ertl-Wagner B, Laurent S, Krumbholz M, Breithaupt C, Högen T, Straube A, Giese A, Hohlfeld R, Lassmann H, Meinl E, Kümpfel T. Histopathology and clinical course of MOG-antibody-associated encephalomyelitis. Ann Clin Transl Neurol. 2015;2:295–301.
Marti Fernandez I, Macrini C, Krumbholz M, Hensbergen PJ, Hipgrave Ederveen AL, Winklmeier S, Vural A, Kurne A, Jenne D, Kamp F, Gerdes LA, Hohlfeld R, Wuhrer M, Kümpfel T, Meinl E. The glycosylation site of myelin oligodendrocyte glycoprotein affects autoantibody recognition in a large proportion of patients. Front Immunol. 2019;10:1189.
Allamargot C, Gardinier MV. Alternative isoforms of myelin/oligodendrocyte glycoprotein with variable cytoplasmic domains are expressed in human brain. J Neurochem. 2007;101:298–312.
Ballenthin PA, Gardinier MV. Myelin/oligodendrocyte glycoprotein is alternatively spliced in humans but not mice. J Neurosci Res. 1996;46:271–281.
Pham-Dinh D, Della Gaspera B, Kerlero de Rosbo N, Dautigny A. Structure of the human myelin/oligodendrocyte glycoprotein gene and multiple alternative spliced isoforms. Genomics. 1995;29:345–352.
Boyle LH, Traherne JA, Plotnek G, Ward R, Trowsdale J. Splice variation in the cytoplasmic domains of myelin oligodendrocyte glycoprotein affects its cellular localisation and transport. J Neurochem. 2007;102:1853–1862.
Macrini C, Gerhards R, Winklmeier S, Bergmann L, Mader S, Spadaro M, Vural A, Smolle M, Hohlfeld R, Kümpfel T, Lichtenthaler SF, Franquelim HG, Jenne D, Meinl E. Features of MOG required for recognition by patients with MOG antibody-associated disorders. Brain. 2021;144:2375–2389.
Schanda K, Peschl P, Lerch M, Seebacher B, Mindorf S, Ritter N, Probst M, Hegen H, Di Pauli F, Wendel E-M, Lechner C, Baumann M, Mariotto S, Ferrari S, Saiz A, Farrell M, Leite MIS, Irani SR, Palace J, Lutterotti A, Kümpfel T, Vukusic S, Marignier R, Waters P, Rostasy K, Berger T, Probst C, Höftberger R, Reindl M. Differential binding of autoantibodies to MOG isoforms in inflammatory demyelinating diseases. Neurol Neuroimmunol Neuroinflamm. 2021;8:e1027.
Linington C, Lassmann H. Antibody responses in chronic relapsing experimental allergic encephalomyelitis: correlation of serum demyelinating activity with antibody titre to the myelin/oligodendrocyte glycoprotein (MOG). J Neuroimmunol. 1987;17:61–69.
Linington C, Berger T, Perry L, Weerth S, Hinze-Selch D, Zhang Y, Lu HC, Lassmann H, Wekerle H. T cells specific for the myelin oligodendrocyte glycoprotein mediate an unusual autoimmune inflammatory response in the central nervous system. Eur J Immunol. 1993;23:1364–1372.
Lassmann H, Brunner C, Bradl M, Linington C. Experimental allergic encephalomyelitis: the balance between encephalitogenic T lymphocytes and demyelinating antibodies determines size and structure of demyelinated lesions. Acta Neuropathol. 1988;75:566–576.
Amor S, Groome N, Linington C, Morris MM, Dornmair K, Gardinier MV, Matthieu JM, Baker D. Identification of epitopes of myelin oligodendrocyte glycoprotein for the induction of experimental allergic encephalomyelitis in SJL and Biozzi AB/H mice. J Immunol. 1994;153:4349–4356.
Krishnamoorthy G, Wekerle H. EAE: an immunologist's magic eye. Eur J Immunol. 2009;39:2031–2035.
Grant-Peters M, Passos GRD, Yeung H-Y, Jacob A, Huda S, Leite MI, Dendrou CA, Palace J. No strong HLA association with MOG antibody disease in the UK population. Ann Clin Transl Neurol. 2021;8:1502–1507.
Bruijstens AL, Wong YYM, van Pelt DE, van der Linden PJE, Haasnoot GW, Hintzen RQ, Claas FHJ, Neuteboom RF, Wokke BHA. HLA association in MOG-IgG- and AQP4-IgG-related disorders of the CNS in the Dutch population. Neurol Neuroimmunol Neuroinflamm. 2020;7:e702.
Sun X, Qiu W, Wang J, Wang S, Wang Y, Zhong X, Liu C, Cui C, Hong H, Yang H, Li X-J, Lu Z, Hu X, Kermode AG, Peng L. Myelin oligodendrocyte glycoprotein-associated disorders are associated with HLA subtypes in a Chinese paediatric-onset cohort. J Neurol Neurosurg Psychiatry. 2020;91:733–739.
Nakamura Y, Nakajima H, Tani H, Hosokawa T, Ishida S, Kimura F, Kaneko K, Takahashi T, Nakashima I. Anti-MOG antibody-positive ADEM following infectious mononucleosis due to a primary EBV infection: a case report. BMC Neurol. 2017;17:76.
Sato R, Okanari K, Maeda T, Kaneko K, Takahashi T, Kenji I. Postinfectious acute disseminated encephalomyelitis associated with antimyelin oligodendrocyte glycoprotein antibody. Child Neurol Open. 2020;7:2329048X20942442.
Nakamura M, Iwasaki Y, Takahashi T, Kaneko K, Nakashima I, Kunieda T, Kaneko S, Kusaka H. A case of MOG antibody-positive bilateral optic neuritis and meningoganglionitis following a genital herpes simplex virus infection. Mult Scler Relat Disord. 2017;17:148–150.
Choi SJ, Oh DA, Chun W, Kim SM. The relationship between anti-myelin oligodendrocyte glycoprotein antibody-associated disease and the rubella virus. J Clin Neurol. 2018;14:598–600.
Zhou S, Jones-Lopez EC, Soneji DJ, Azevedo CJ, Patel VR. Myelin oligodendrocyte glycoprotein antibody-associated optic neuritis and myelitis in COVID-19. J Neuroophthalmol. 2020;40:398–402.
Di Pauli F, Morschewsky P, Berek K, Auer M, Bauer A, Berger T, Bsteh G, Rhomberg P, Schanda K, Zinganell A, Deisenhammer F, Reindl M, Hegen H. Myelin oligodendrocyte glycoprotein antibody-associated disease and varicella zoster virus infection—frequency of an association. Front Immunol. 2021;12:769653.
Wildemann B, Jarius S, Franz J, Ruprecht K, Reindl M, Stadelmann C. MOG-expressing teratoma followed by MOG-IgG-positive optic neuritis. Acta Neuropathol. 2021;141:127–131.
Redenbaugh V, Flanagan EP, Floris V, Zara P, Bhatti MT, Sanchez F, Koster M, Mariotto S, Pittock SJ, Chen JJ, Cauli A, Solla P, Sechi E. Exposure to TNF inhibitors is rare at MOGAD presentation. J Neurol Sci. 2022;432:120044.
Kipnis J. Multifaceted interactions between adaptive immunity and the central nervous system. Science. 2016;353:766–771.
Wekerle H. Breaking ignorance: the case of the brain. Curr Top Microbiol Immunol. 2006;305:25–50.
Louveau A, Harris TH, Kipnis J. Revisiting the mechanisms of CNS immune privilege. Trends Immunol. 2015;36:569–577.
Traka M, Podojil JR, McCarthy DP, Miller SD, Popko B. Oligodendrocyte death results in immune-mediated CNS demyelination. Nat Neurosci. 2016;19:65–74.
Lopez JA, Denkova M, Ramanathan S, Dale RC, Brilot F. Pathogenesis of autoimmune demyelination: from multiple sclerosis to neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody-associated disease. Clin Transl Immunol. 2021;10:e1316.
Louveau A, Herz J, Alme MN, Salvador AF, Dong MQ, Viar KE, Herod SG, Knopp J, Setliff JC, Lupi AL, Da Mesquita S, Frost EL, Gaultier A, Harris TH, Cao R, Hu S, Lukens JR, Smirnov I, Overall CC, Oliver G, Kipnis J. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci. 2018;21:1380–1391.
Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, Detmar M, Wiig H, Alitalo K. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med. 2015;212:991–999.
Alves de Lima K, Rustenhoven J, Kipnis J. Meningeal immunity and its function in maintenance of the central nervous system in health and disease. Annu Rev Immunol. 2020;38:597–620.
Norris GT, Kipnis J. Immune cells and CNS physiology: microglia and beyond. J Exp Med. 2019;216:60–70.
Louveau A, Plog BA, Antila S, Alitalo K, Nedergaard M, Kipnis J. Understanding the functions and relationships of the glymphatic system and meningeal lymphatics. J Clin Invest. 2017;127:3210–3219.
Korn T, Kallies A. T cell responses in the central nervous system. Nat Rev Immunol. 2017;17:179–194.
Schetters STT, Gomez-Nicola D, Garcia-Vallejo JJ, van Kooyk Y. Neuroinflammation: microglia and T cells get ready to Tango. Front Immunol. 2017;8:1905.
de Vos AF, van Meurs M, Brok HP, Boven LA, Hintzen RQ, van der Valk P, Ravid R, Rensing S, Boon L, 't Hart BA, Laman JD. Transfer of central nervous system autoantigens and presentation in secondary lymphoid organs. J Immunol. 2002;169:5415–5423.
Na S-Y, Hermann A, Sanchez-Ruiz M, Storch A, Deckert M, Hünig T. Oligodendrocytes enforce immune tolerance of the uninfected brain by purging the peripheral repertoire of autoreactive CD8+ T cells. Immunity. 2012;37:134–146.
Fletcher AL, Malhotra D, Turley SJ. Lymph node stroma broaden the peripheral tolerance paradigm. Trends Immunol. 2011;32:12–18.
Rouhani SJ, Eccles JD, Riccardi P, Peske JD, Tewalt EF, Cohen JN, Liblau R, Mäkinen T, Engelhard VH. Roles of lymphatic endothelial cells expressing peripheral tissue antigens in CD4 T-cell tolerance induction. Nat Commun. 2015;6:6771.
Louveau A, Da Mesquita S, Kipnis J. Lymphatics in neurological disorders: a neuro-lympho-vascular component of multiple sclerosis and Alzheimer's disease? Neuron. 2016;91:957–973.
Guggenmos J, Schubart AS, Ogg S, Andersson M, Olsson T, Mather IH, Linington C. Antibody cross-reactivity between myelin oligodendrocyte glycoprotein and the milk protein butyrophilin in multiple sclerosis. J Immunol. 2004;172:661–668.
Derbinski J, Schulte A, Kyewski B, Klein L. Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self. Nat Immunol. 2001;2:1032–1039.
Pagany M, Jagodic M, Schubart A, Pham-Dinh D, Bachelin C, Baron van Evercooren A, Lachapelle F, Olsson T, Linington C. Myelin oligodendrocyte glycoprotein is expressed in the peripheral nervous system of rodents and primates. Neurosci Lett. 2003;350:165–168.
Delarasse C, Daubas P, Mars LT, Vizler C, Litzenburger T, Iglesias A, Bauer J, Della Gaspera B, Schubart A, Decker L, Dimitri D, Roussel G, Dierich A, Amor S, Dautigny A, Liblau R, Pham-Dinh D. Myelin/oligodendrocyte glycoprotein–deficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice. J Clin Invest. 2003;112:544–553.
Na S-Y, Krishnamoorthy G. Targeted expression of myelin autoantigen in the periphery induces antigen-specific T and B cell tolerance and ameliorates autoimmune disease. Front Immunol. 2021;12:668487.
Krienke C, Kolb L, Diken E, Streuber M, Kirchhoff S, Bukur T, Akilli-Öztürk Ö, Kranz LM, Berger H, Petschenka J, Diken M, Kreiter S, Yogev N, Waisman A, Karikó K, Türeci Ö, Sahin U. A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis. Science. 2021;371:145–153.
Mundt S, Greter M, Flügel A, Becher B. The CNS immune landscape from the viewpoint of a T cell. Trends Neurosci. 2019;42:667–679.
Kyratsous NI, Bauer IJ, Zhang G, Pesic M, Bartholomäus I, Mues M, Fang P, Wörner M, Everts S, Ellwart JW, Watt JM, Potter BVL, Hohlfeld R, Wekerle H, Kawakami N. Visualizing context-dependent calcium signaling in encephalitogenic T cells in vivo by two-photon microscopy. Proc Natl Acad Sci U S A. 2017;114:E6381–E6389.
Engelhardt B, Ransohoff RM. Capture, crawl, cross: the T cell code to breach the blood-brain barriers. Trends Immunol. 2012;33:579–589.
Flügel A, Berkowicz T, Ritter T, Labeur M, Jenne DE, Li Z, Ellwart JW, Willem M, Lassmann H, Wekerle H. Migratory activity and functional changes of green fluorescent effector cells before and during experimental autoimmune encephalomyelitis. Immunity. 2001;14:547–560.
Kunkl M, Frascolla S, Amormino C, Volpe E, Tuosto L. T helper cells: the modulators of inflammation in multiple sclerosis. Cells. 2020;9:E482.
Huang X, Hussain B, Chang J. Peripheral inflammation and blood-brain barrier disruption: effects and mechanisms. CNS Neurosci Ther. 2021;27:36–47.
Fujihara K, Bennett JL, de Seze J, Haramura M, Kleiter I, Weinshenker BG, Kang D, Mughal T, Yamamura T. Interleukin-6 in neuromyelitis optica spectrum disorder pathophysiology. Neurol Neuroimmunol Neuroinflamm. 2020;7:e841.
Hickey WF, Kimura H. Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science. 1988;239:290–292.
Dong Y, Yong VW. When encephalitogenic T cells collaborate with microglia in multiple sclerosis. Nat Rev Neurol. 2019;15:704–717.
Greter M, Heppner FL, Lemos MP, Odermatt BM, Goebels N, Laufer T, Noelle RJ, Becher B. Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat Med. 2005;11:328–334.
Jordão MJC, Sankowski R, Brendecke SM, Sagar, Locatelli G, Tai Y-H, Tay TL, Schramm E, Armbruster S, Hagemeyer N, Groß O, Mai D, Çiçek Ö, Falk T, Kerschensteiner M, Grün D, Prinz M. Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation. Science. 2019;363:eaat7554.
Mrdjen D, Pavlovic A, Hartmann FJ, Schreiner B, Utz SG, Leung BP, Lelios I, Heppner FL, Kipnis J, Merkler D, Greter M, Becher B. High-dimensional single-cell mapping of central nervous system immune cells reveals distinct myeloid subsets in health, aging, and disease. Immunity. 2018;48:380–395.e6.
Goldmann T, Wieghofer P, Jordão MJC, Prutek F, Hagemeyer N, Frenzel K, Amann L, Staszewski O, Kierdorf K, Krueger M, Locatelli G, Hochgerner H, Zeiser R, Epelman S, Geissmann F, Priller J, Rossi FMV, Bechmann I, Kerschensteiner M, Linnarsson S, Jung S, Prinz M. Origin, fate and dynamics of macrophages at central nervous system interfaces. Nat Immunol. 2016;17:797–805.
Kothur K, Wienholt L, Tantsis EM, Earl J, Bandodkar S, Prelog K, Tea F, Ramanathan S, Brilot F, Dale RC. B cell, Th17, and neutrophil related cerebrospinal fluid cytokine/chemokines are elevated in MOG antibody associated demyelination. PLoS One. 2016;11:e0149411.
Kaneko K, Sato DK, Nakashima I, Ogawa R, Akaishi T, Takai Y, Nishiyama S, Takahashi T, Misu T, Kuroda H, Tanaka S, Nomura K, Hashimoto Y, Callegaro D, Steinman L, Fujihara K, Aoki M. CSF cytokine profile in MOG-IgG+ neurological disease is similar to AQP4-IgG+ NMOSD but distinct from MS: a cross-sectional study and potential therapeutic implications. J Neurol Neurosurg Psychiatry. 2018;89:927–936.
Hofer LS, Mariotto S, Wurth S, Ferrari S, Mancinelli CR, Delogu R, Monaco S, Gajofatto A, Schwaiger C, Rostasy K, Deisenhammer F, Höftberger R, Berger T, Reindl M. Distinct serum and cerebrospinal fluid cytokine and chemokine profiles in autoantibody-associated demyelinating diseases. Mult Scler J Exp Transl Clin. 2019;5:2055217319848463.
Elsbernd PM, Hoffman WR, Carter JL, Wingerchuk DM. Interleukin-6 inhibition with tocilizumab for relapsing MOG-IgG associated disorder (MOGAD): a case-series and review. Mult Scler Relat Disord. 2021;48:102696.
Rigal J, Pugnet G, Ciron J, Lépine Z, Biotti D. Off-label use of tocilizumab in neuromyelitis optica spectrum disorders and MOG-antibody-associated diseases: a case-series. Mult Scler Relat Disord. 2020;46:102483.
Ringelstein M, Ayzenberg I, Lindenblatt G, Fischer K, Gahlen A, Novi G, Hayward-Könnecke H, Schippling S, Rommer PS, Kornek B, Zrzavy T, Biotti D, Ciron J, Audoin B, Berthele A, Giglhuber K, Zephir H, Kümpfel T, Berger R, Röther J, Häußler V, Stellmann J-P, Whittam D, Jacob A, Kraemer M, Gueguen A, Deschamps R, Bayas A, Hümmert MW, Trebst C, Haarmann A, Jarius S, Wildemann B, Grothe M, Siebert N, Ruprecht K, Paul F, Collongues N, Marignier R, Levy M, Karenfort M, Deppe M, Albrecht P, Hellwig K, Gold R, Hartung H-P, Meuth SG, Kleiter I, Aktas O; Neuromyelitis Optica Study Group NEMOS. Interleukin-6 receptor blockade in treatment-refractory MOG-IgG-associated disease and neuromyelitis optica spectrum disorders. Neurol Neuroimmunol Neuroinflamm. 2022;9:e1100.
Mariotto S, Ferrari S, Gastaldi M, Franciotta D, Sechi E, Capra R, Mancinelli C, Schanda K, Alberti D, Orlandi R, Bombardi R, Zuliani L, Zoccarato M, Benedetti MD, Tanel R, Calabria F, Rossi F, Pavone A, Grazian L, Sechi G, Batzu L, Murdeu N, Janes F, Fetoni V, Fulitano D, Stenta G, Federle L, Cantalupo G, Reindl M, Monaco S, Gajofatto A. Neurofilament light chain serum levels reflect disease severity in MOG-Ab associated disorders. J Neurol Neurosurg Psychiatry. 2019;90:1293–1296.
Kaneko K, Sato DK, Nakashima I, Nishiyama S, Tanaka S, Marignier R, Hyun J-W, Oliveira LMd, Reindl M, Seifert-Held T, Sepulveda M, Siritho S, Waters PJ, Kurosawa K, Akaishi T, Kuroda H, Misu T, Prayoonwiwat N, Berger T, Saiz A, Kim HJ, Nomura K, Callegaro D, Fujihara K, Aoki M. Myelin injury without astrocytopathy in neuroinflammatory disorders with MOG antibodies. J Neurol Neurosurg Psychiatry. 2016;87:1257–1259.
Hofer LS, Ramberger M, Gredler V, Pescoller AS, Rostásy K, Sospedra M, Hegen H, Berger T, Lutterotti A, Reindl M. Comparative analysis of T-cell responses to aquaporin-4 and myelin oligodendrocyte glycoprotein in inflammatory demyelinating central nervous system diseases. Front Immunol. 2020;11:1188.
Bronge M, Ruhrmann S, Carvalho-Queiroz C, Nilsson OB, Kaiser A, Holmgren E, Macrini C, Winklmeier S, Meinl E, Brundin L, Khademi M, Olsson T, Gafvelin G, Grönlund H. Myelin oligodendrocyte glycoprotein revisited-sensitive detection of MOG-specific T-cells in multiple sclerosis. J Autoimmun. 2019;102:38–49.
Jain RW, Yong VW. B cells in central nervous system disease: diversity, locations and pathophysiology. Nat Rev Immunol. 2022;22:513–524.
Jelcic I, Al Nimer F, Wang J, Lentsch V, Planas R, Jelcic I, Madjovski A, Ruhrmann S, Faigle W, Frauenknecht K, Pinilla C, Santos R, Hammer C, Ortiz Y, Opitz L, Grönlund H, Rogler G, Boyman O, Reynolds R, Lutterotti A, Khademi M, Olsson T, Piehl F, Sospedra M, Martin R. Memory B cells activate brain-homing, autoreactive CD4+ T cells in multiple sclerosis. Cell. 2018;175:85–100.e23.
Archambault AS, Carrero JA, Barnett LG, McGee NG, Sim J, Wright JO, Raabe T, Chen P, Ding H, Allenspach EJ, Dragatsis I, Laufer TM, Wu GF. Cutting edge: conditional MHC class II expression reveals a limited role for B cell antigen presentation in primary and secondary CD4 T cell responses. J Immunol. 2013;191:545–550.
Molnarfi N, Schulze-Topphoff U, Weber MS, Patarroyo JC, Prod'homme T, Varrin-Doyer M, Shetty A, Linington C, Slavin AJ, Hidalgo J, Jenne DE, Wekerle H, Sobel RA, Bernard CCA, Shlomchik MJ, Zamvil SS. MHC class II-dependent B cell APC function is required for induction of CNS autoimmunity independent of myelin-specific antibodies. J Exp Med. 2013;210:2921–2937.
Winklmeier S, Schlüter M, Spadaro M, Thaler FS, Vural A, Gerhards R, Macrini C, Mader S, Kurne A, Inan B, Karabudak R, Özbay FG, Esendagli G, Hohlfeld R, Kümpfel T, Meinl E. Identification of circulating MOG-specific B cells in patients with MOG antibodies. Neurol Neuroimmunol Neuroinflamm. 2019;6:625.
Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM. B cells regulate autoimmunity by provision of IL-10. Nat Immunol. 2002;3:944–950.
Rojas OL, Pröbstel A-K, Porfilio EA, Wang AA, Charabati M, Sun T, Lee DSW, Galicia G, Ramaglia V, Ward LA, Leung LYT, Najafi G, Khaleghi K, Garcillán B, Li A, Besla R, Naouar I, Cao EY, Chiaranunt P, Burrows K, Robinson HG, Allanach JR, Yam J, Luck H, Campbell DJ, Allman D, Brooks DG, Tomura M, Baumann R, Zamvil SS, Bar-Or A, Horwitz MS, Winer DA, Mortha A, Mackay F, Prat A, Osborne LC, Robbins C, Baranzini SE, Gommerman JL. Recirculating intestinal IgA-producing cells regulate neuroinflammation via IL-10. Cell. 2019;177:492–493. e18.
Li X, Wang L, Zhou L, ZhangBao J, Miao MZ, Lu C, Lu J, Quan C. The imbalance between regulatory and memory B cells accompanied by an increased number of circulating T-follicular helper cells in MOG-antibody-associated demyelination. Mult Scler Relat Disord. 2019;36:101397.
Cobo-Calvo A, Sepúlveda M, Rollot F, Armangué T, Ruiz A, Maillart E, Papeix C, Audoin B, Zephir H, Biotti D, Ciron J, Durand-Dubief F, Collongues N, Ayrignac X, Labauge P, Thouvenot E, Bourre B, Montcuquet A, Cohen M, Deschamps R, Solà-Valls N, Llufriu S, De Seze J, Blanco Y, Vukusic S, Saiz A, Marignier R. Evaluation of treatment response in adults with relapsing MOG-Ab-associated disease. J Neuroinflammation. 2019;16:134.
Chen JJ, Flanagan EP, Bhatti MT, Jitprapaikulsan J, Dubey D, Lopez Chiriboga ASS, Fryer JP, Weinshenker BG, McKeon A, Tillema J-M, Lennon VA, Lucchinetti CF, Kunchok A, McClelland CM, Lee MS, Bennett JL, Pelak VS, van Stavern G, Adesina O-OO, Eggenberger ER, Acierno MD, Wingerchuk DM, Lam BL, Moss H, Beres S, Gilbert AL, Shah V, Armstrong G, Heidary G, Cestari DM, Stiebel-Kalish H, Pittock SJ. Steroid-sparing maintenance immunotherapy for MOG-IgG associated disorder. Neurology. 2020;95:e111–e120.
Montcuquet A, Collongues N, Papeix C, Zephir H, Audoin B, Laplaud D, Bourre B, Brochet B, Camdessanche J-P, Labauge P, Moreau T, Brassat D, Stankoff B, de Seze J, Vukusic S, Marignier R; NOMADMUS Study Group and the Observatoire Francais de la Sclerose en Plaques OFSEP. Effectiveness of mycophenolate mofetil as first-line therapy in AQP4-IgG, MOG-IgG, and seronegative neuromyelitis optica spectrum disorders. Mult Scler. 2017;23:1377–1384.
Nepal G, Kharel S, Coghlan MA, Rayamajhi P, Ojha R. Safety and efficacy of rituximab for relapse prevention in myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG)-associated disorders (MOGAD): a systematic review and meta-analysis. J Neuroimmunol. 2022;364:577812.
Whittam DH, Cobo-Calvo A, Lopez-Chiriboga AS, Pardo S, Gornall M, Cicconi S, Brandt A, Berek K, Berger T, Jelcic I, Gombolay G, Oliveira LM, Callegaro D, Kaneko K, Misu T, Capobianco M, Gibbons E, Karthikeayan V, Brochet B, Audoin B, Mathey G, Laplaud D, Thouvenot E, Cohen M, Tourbah A, Maillart E, Ciron J, Deschamps R, Biotti D, Rostasy K, Neuteboom R, Hemingway C, Forsyth R, Matiello M, Webb S, Hunt D, Murray K, Hacohen Y, Lim M, Leite MI, Palace J, Solomon T, Lutterotti A, Fujihara K, Nakashima I, Bennett JL, Pandit L, Chitnis T, Weinshenker BG, Wildemann B, Sato DK, Kim SH, Huda S, Kim HJ, Reindl M, Levy M, Jarius S, Tenembaum S, Paul F, Pittock S, Marignier R, Jacob A. Treatment of MOG-IgG-associated disorder with rituximab: an international study of 121 patients. Mult Scler Relat Disord. 2020;44:102251.
Graf J, Mares J, Barnett M, Aktas O, Albrecht P, Zamvil SS, Hartung H-P. Targeting B cells to modify MS, NMOSD, and MOGAD: part 2. Neurol Neuroimmunol Neuroinflamm. 2021;8:e919.
Spadaro M, Winklmeier S, Beltrán E, Macrini C, Höftberger R, Schuh E, Thaler FS, Gerdes LA, Laurent S, Gerhards R, Brändle S, Dornmair K, Breithaupt C, Krumbholz M, Moser M, Krishnamoorthy G, Kamp F, Jenne D, Hohlfeld R, Kümpfel T, Lassmann H, Kawakami N, Meinl E. Pathogenicity of human antibodies against myelin oligodendrocyte glycoprotein. Ann Neurol. 2018;84:315–328.
Jarius S, Pellkofer H, Siebert N, Korporal-Kuhnke M, Hümmert MW, Ringelstein M, Rommer PS, Ayzenberg I, Ruprecht K, Klotz L, Asgari N, Zrzavy T, Höftberger R, Tobia R, Buttmann M, Fechner K, Schanda K, Weber M, Asseyer S, Haas J, Lechner C, Kleiter I, Aktas O, Trebst C, Rostasy K, Reindl M, Kümpfel T, Paul F, Wildemann B; In Cooperation With the Neuromyelitis Optica Study Group NEMOS. Cerebrospinal fluid findings in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies. Part 1: results from 163 lumbar punctures in 100 adult patients. J Neuroinflammation. 2020;17:261.
Mariotto S, Gajofatto A, Batzu L, Delogu R, Sechi G, Leoni S, Pirastru MI, Bonetti B, Zanoni M, Alberti D, Schanda K, Monaco S, Reindl M, Ferrari S. Relevance of antibodies to myelin oligodendrocyte glycoprotein in CSF of seronegative cases. Neurology. 2019;93:e1867–e1872.
Kwon YN, Kim B, Kim J-S, Mo H, Choi K, Oh S-I, Kim J-E, Nam T-S, Sohn EH, Heo SH, Kim SB, Park K-C, Yoon SS, Oh J, Baek S-H, Kim B-J, Park KS, Sung J-J, Jung JH, Kim S-J, Park S-H, Waters P, Kim S-M. Myelin oligodendrocyte glycoprotein-immunoglobulin G in the CSF: clinical implication of testing and association with disability. Neurol Neuroimmunol Neuroinflamm. 2022;9:e1095.
Mariotto S, Ferrari S, Monaco S, Benedetti MD, Schanda K, Alberti D, Farinazzo A, Capra R, Mancinelli C, De Rossi N, Bombardi R, Zuliani L, Zoccarato M, Tanel R, Bonora A, Turatti M, Calabrese M, Polo A, Pavone A, Grazian L, Sechi G, Sechi E, Urso D, Delogu R, Janes F, Deotto L, Cadaldini M, Bianchi MR, Cantalupo G, Reindl M, Gajofatto A. Clinical spectrum and IgG subclass analysis of anti-myelin oligodendrocyte glycoprotein antibody-associated syndromes: a multicenter study. J Neurol. 2017;264:2420–2430.
Piddlesden SJ, Lassmann H, Zimprich F, Morgan BP, Linington C. The demyelinating potential of antibodies to myelin oligodendrocyte glycoprotein is related to their ability to fix complement. Am J Pathol. 1993;143:555–564.
Saadoun S, Waters P, Owens GP, Bennett JL, Vincent A, Papadopoulos MC. Neuromyelitis optica MOG-IgG causes reversible lesions in mouse brain. Acta Neuropathol Commun. 2014;2:35.
Keller CW, Lopez JA, Wendel E-M, Ramanathan S, Gross CC, Klotz L, Reindl M, Dale RC, Wiendl H, Rostásy K, Brilot F, Lünemann JD. Complement activation is a prominent feature of MOGAD. Ann Neurol. 2021;90:976–982.
Dale RC, Tantsis EM, Merheb V, Kumaran R-YA, Sinmaz N, Pathmanandavel K, Ramanathan S, Booth DR, Wienholt LA, Prelog K, Clark DR, Guillemin GJ, Lim CK, Mathey EK, Brilot F. Antibodies to MOG have a demyelination phenotype and affect oligodendrocyte cytoskeleton. Neurol Neuroimmunol Neuroinflamm. 2014;1:e12.
Marta CB, Taylor CM, Coetzee T, Kim T, Winkler S, Bansal R, Pfeiffer SE. Antibody cross-linking of myelin oligodendrocyte glycoprotein leads to its rapid repartitioning into detergent-insoluble fractions, and altered protein phosphorylation and cell morphology. J Neurosci. 2003;23:5461–5471.
Brilot F, Dale RC, Selter RC, Grummel V, Kalluri SR, Aslam M, Busch V, Zhou D, Cepok S, Hemmer B. Antibodies to native myelin oligodendrocyte glycoprotein in children with inflammatory demyelinating central nervous system disease. Ann Neurol. 2009;66:833–842.
Flach A-C, Litke T, Strauss J, Haberl M, Gómez CC, Reindl M, Saiz A, Fehling H-J, Wienands J, Odoardi F, Lühder F, Flügel A. Autoantibody-boosted T-cell reactivation in the target organ triggers manifestation of autoimmune CNS disease. Proc Natl Acad Sci U S A. 2016;113:3323–3328.
Kinzel S, Lehmann-Horn K, Torke S, Häusler D, Winkler A, Stadelmann C, Payne N, Feldmann L, Saiz A, Reindl M, Lalive PH, Bernard CC, Brück W, Weber MS. Myelin-reactive antibodies initiate T cell-mediated CNS autoimmune disease by opsonization of endogenous antigen. Acta Neuropathol. 2016;132:43–58.
Höftberger R, Guo Y, Flanagan EP, Lopez-Chiriboga AS, Endmayr V, Hochmeister S, Joldic D, Pittock SJ, Tillema JM, Gorman M, Lassmann H, Lucchinetti CF. The pathology of central nervous system inflammatory demyelinating disease accompanying myelin oligodendrocyte glycoprotein autoantibody. Acta Neuropathol. 2020;139:875–892.
Takai Y, Misu T, Kaneko K, Chihara N, Narikawa K, Tsuchida S, Nishida H, Komori T, Seki M, Komatsu T, Nakamagoe K, Ikeda T, Yoshida M, Takahashi T, Ono H, Nishiyama S, Kuroda H, Nakashima I, Suzuki H, Bradl M, Lassmann H, Fujihara K, Aoki M; Japan MOG-antibody Disease Consortium. Myelin oligodendrocyte glycoprotein antibody-associated disease: an immunopathological study. Brain. 2020;143:1431–1446.
Shu Y, Long Y, Wang S, Hu W, Zhou J, Xu H, Chen C, Ou Y, Lu Z, Lau AY, Yu X, Kermode AG, Qiu W. Brain histopathological study and prognosis in MOG antibody-associated demyelinating pseudotumor. Ann Clin Transl Neurol. 2019;6:392–396.
Zhou L, Huang Y, Li H, Fan J, ZhangBao J, Yu H, Li Y, Lu J, Zhao C, Lu C, Wang M, Quan C. MOG-antibody associated demyelinating disease of the CNS: a clinical and pathological study in Chinese Han patients. J Neuroimmunol. 2017;305:19–28.
Jarius S, Metz I, König FB, Ruprecht K, Reindl M, Paul F, Brück W, Wildemann B. 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. Mult Scler. 2016;22:1541–1549.
Körtvélyessy P, Breu M, Pawlitzki M, Metz I, Heinze H-J, Matzke M, Mawrin C, Rommer P, Kovacs GG, Mitter C, Reindl M, Brück W, Wandinger K-P, Lassmann H, Höftberger R, Leypoldt F. ADEM-like presentation, anti-MOG antibodies, and MS pathology: two case reports. Neurol Neuroimmunol Neuroinflamm. 2017;4:e335.
Sechi E, Krecke KN, Messina SA, Buciuc M, Pittock SJ, Chen JJ, Weinshenker BG, Lopez-Chiriboga AS, Lucchinetti CF, Zalewski NL, Tillema JM, Kunchok A, Monaco S, Morris PP, Fryer JP, Nguyen A, Greenwood T, Syc-Mazurek SB, Keegan BM, Flanagan EP. Comparison of MRI lesion evolution in different central nervous system demyelinating disorders. Neurology. 2021;97:e1097–e1109.
ZhangBao J, Huang W, Zhou L, Wang L, Chang X, Lu C, Zhao C, Lu J, Quan C. Myelitis in inflammatory disorders associated with myelin oligodendrocyte glycoprotein antibody and aquaporin-4 antibody: a comparative study in Chinese Han patients. Eur J Neurol. 2021;28:1308–1315.
Zhao G, Chen Q, Huang Y, Li Z, Sun X, Lu P, Yan S, Wang M, Tian G. Clinical characteristics of myelin oligodendrocyte glycoprotein seropositive optic neuritis: a cohort study in Shanghai, China. J Neurol. 2018;265:33–40.
Liu H, Zhou H, Wang J, Sun M, Teng D, Song H, Xu Q, Wei S. The prevalence and prognostic value of myelin oligodendrocyte glycoprotein antibody in adult optic neuritis. J Neurol Sci. 2019;396:225–231.
Deschamps R, Lecler A, Lamirel C, Aboab J, Gueguen A, Bensa C, Vignal C, Gout O. Etiologies of acute demyelinating optic neuritis: an observational study of 110 patients. Eur J Neurol. 2017;24:875–879.
Zhao Y, Tan S, Chan TCY, Xu Q, Zhao J, Teng D, Fu H, Wei S. Clinical features of demyelinating optic neuritis with seropositive myelin oligodendrocyte glycoprotein antibody in Chinese patients. Br J Ophthalmol. 2018;102:1372–1377.
Soelberg K, Jarius S, Skejoe H, Engberg H, Mehlsen JJ, Nilsson AC, Madsen JS, Reindl M, Wildemann B, Grauslund J, Kyvik KO, Smith TJ, Lillevang ST, Paul F, Weinshenker BG, Asgari N. A population-based prospective study of optic neuritis. Mult Scler. 2017;23:1893–1901.
Ducloyer J-B, Caignard A, Aidaoui R, Ollivier Y, Plubeau G, Santos-Moskalyk S, Porphyre L, Le Jeune C, Bihl L, Alamine S, Marignier R, Bourcier R, Ducloyer M, Weber M, Le Meur G, Wiertlewski S, Lebranchu P. MOG-Ab prevalence in optic neuritis and clinical predictive factors for diagnosis. Br J Ophthalmol. 2020;104:842–845.
Jarius S, Ruprecht K, Kleiter I, Borisow N, Asgari N, Pitarokoili K, Pache F, Stich O, Beume L-A, Hümmert MW, Ringelstein M, Trebst C, Winkelmann A, Schwarz A, Buttmann M, Zimmermann H, Kuchling J, Franciotta D, Capobianco M, Siebert E, Lukas C, Korporal-Kuhnke M, Haas J, Fechner K, Brandt AU, Schanda K, Aktas O, Paul F, Reindl M, Wildemann B; In cooperation With the Neuromyelitis Optica Study Group NEMOS. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. J Neuroinflammation. 2016;13:280.
Chen JJ, Flanagan EP, Jitprapaikulsan J, López-Chiriboga ASS, Fryer JP, Leavitt JA, Weinshenker BG, McKeon A, Tillema J-M, Lennon VA, Tobin WO, Keegan BM, Lucchinetti CF, Kantarci OH, McClelland CM, Lee MS, Bennett JL, Pelak VS, Chen Y, VanStavern G, Adesina O-OO, Eggenberger ER, Acierno MD, Wingerchuk DM, Brazis PW, Sagen J, Pittock SJ. Myelin oligodendrocyte glycoprotein antibody-positive optic neuritis: clinical characteristics, radiologic clues, and outcome. Am J Ophthalmol. 2018;195:8–15.
Liu H, Zhou H, Wang J, Xu Q, Wei S. Antibodies to myelin oligodendrocyte glycoprotein in chronic relapsing inflammatory optic neuropathy. Br J Ophthalmol. 2019;103:1423–1428.
Vosoughi AR, Ling J, Tam KT, Blackwood J, Micieli JA. Ophthalmic manifestations of myelin oligodendrocyte glycoprotein-IgG-associated disorder other than optic neuritis: a systematic review. Br J Ophthalmol. 2021;105:1591–1598.
Chen JJ, Sotirchos ES, Henderson AD, Vasileiou ES, Flanagan EP, Bhatti MT, Jamali S, Eggenberger ER, Dinome M, Frohman LP, Arnold AC, Bonelli L, Seleme N, Mejia-Vergara AJ, Moss HE, Padungkiatsagul T, Stiebel-Kalish H, Lotan I, Hellmann MA, Hodge D, Oertel FC, Paul F, Saidha S, Calabresi PA, Pittock SJ. OCT retinal nerve fiber layer thickness differentiates acute optic neuritis from MOG antibody-associated disease and multiple sclerosis: RNFL thickening in acute optic neuritis from MOGAD vs MS. Mult Scler Relat Disord. 2022;58:103525.
Sotirchos ES, Filippatou A, Fitzgerald KC, Salama S, Pardo S, Wang J, Ogbuokiri E, Cowley NJ, Pellegrini N, Murphy OC, Mealy MA, Prince JL, Levy M, Calabresi PA, Saidha S. Aquaporin-4 IgG seropositivity is associated with worse visual outcomes after optic neuritis than MOG-IgG seropositivity and multiple sclerosis, independent of macular ganglion cell layer thinning. Mult Scler. 2020;26:1360–1371.
Yu J, Huang Y, Quan C, Zhou L, ZhangBao J, Wu K, Zong Y, Zhou X, Wang M. Alterations in the retinal vascular network and structure in MOG antibody-associated disease: an optical coherence tomography angiography study. J Neuroophthalmol. 2021;41:e424–e432.
Ramanathan S, Prelog K, Barnes EH, Tantsis EM, Reddel SW, Henderson APD, Vucic S, Gorman MP, Benson LA, Alper G, Riney CJ, Barnett M, Parratt JDE, Hardy TA, Leventer RJ, Merheb V, Nosadini M, Fung VSC, Brilot F, Dale RC. Radiological differentiation of optic neuritis with myelin oligodendrocyte glycoprotein antibodies, aquaporin-4 antibodies, and multiple sclerosis. Mult Scler. 2016;22:470–482.
Tajfirouz D, Padungkiatsagul T, Beres S, Moss HE, Pittock S, Flanagan E, Kunchok A, Shah S, Bhatti MT, Chen JJ. Optic chiasm involvement in AQP-4 antibody-positive NMO and MOG antibody-associated disorder. Mult Scler. 2022;28:149–153.
Akaishi T, Himori N, Takeshita T, Misu T, Takahashi T, Takai Y, Nishiyama S, Fujimori J, Ishii T, Aoki M, Fujihara K, Nakazawa T, Nakashima I. Five-year visual outcomes after optic neuritis in anti-MOG antibody-associated disease. Mult Scler Relat Disord. 2021;56:103222.
Storch MK, Stefferl A, Brehm U, Weissert R, Wallström E, Kerschensteiner M, Olsson T, Linington C, Lassmann H. Autoimmunity to myelin oligodendrocyte glycoprotein in rats mimics the spectrum of multiple sclerosis pathology. Brain Pathol. 1998;8:681–694.
Weissert R, de Graaf KL, Storch MK, Barth S, Linington C, Lassmann H, Olsson T. MHC class II-regulated central nervous system autoaggression and T cell responses in peripheral lymphoid tissues are dissociated in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. J Immunol. 2001;166:7588–7599.
Weissert R, Wallström E, Storch MK, Stefferl A, Lorentzen J, Lassmann H, Linington C, Olsson T. MHC haplotype-dependent regulation of MOG-induced EAE in rats. J Clin Invest. 1998;102:1265–1273.
Bettelli E, Baeten D, Jäger A, Sobel RA, Kuchroo VK. Myelin oligodendrocyte glycoprotein-specific T and B cells cooperate to induce a Devic-like disease in mice. J Clin Invest. 2006;116:2393–2402.
Krishnamoorthy G, Lassmann H, Wekerle H, Holz A. Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell/B cell cooperation. J Clin Invest. 2006;116:2385–2392.
Jin J, Shneyderman M, Smith MD, Gharagozloo M, Sotirchos ES, Calabresi PA. Retinal pathology in spontaneous opticospinal experimental autoimmune encephalitis mice. J Neuroimmunol. 2022;367:577859.
Dietrich M, Aktas O, Hartung H-P, Albrecht P. Assessing the anterior visual pathway in optic neuritis: recent experimental and clinical aspects. Curr Opin Neurol. 2019;32:346–357.
Bettelli E, Pagany M, Weiner HL, Linington C, Sobel RA, Kuchroo VK. Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis. J Exp Med. 2003;197:1073–1081.
Castoldi V, Marenna S, Huang S-C, d'Isa R, Chaabane L, Comi G, Leocani L. Dose-dependent effect of myelin oligodendrocyte glycoprotein on visual function and optic nerve damage in experimental autoimmune encephalomyelitis. J Neurosci Res. 2022;100:855–868.
Petrikowski L, Reinehr S, Haupeltshofer S, Deppe L, Graz F, Kleiter I, Dick HB, Gold R, Faissner S, Joachim SC. Progressive retinal and optic nerve damage in a mouse model of spontaneous opticospinal encephalomyelitis. Front Immunol. 2021;12:759389.
Horstmann L, Kuehn S, Pedreiturria X, Haak K, Pfarrer C, Dick HB, Kleiter I, Joachim SC. Microglia response in retina and optic nerve in chronic experimental autoimmune encephalomyelitis. J Neuroimmunol. 2016;298:32–41.
Bradl M, Reindl M, Lassmann H. Mechanisms for lesion localization in neuromyelitis optica spectrum disorders. Curr Opin Neurol. 2018;31:325–333.
Oertel FC, Sotirchos ES, Zimmermann HG, Motamedi S, Specovius S, Asseyer ES, Chien C, Cook L, Vasileiou E, Filippatou A, Calabresi PA, Saidha S, Pandit L, D'Cunha A, Outteryck O, Zéphir H, Pittock S, Flanagan EP, Bhatti MT, Rommer PS, Bsteh G, Zrzavy T, Kuempfel T, Aktas O, Ringelstein M, Albrecht P, Ayzenberg I, Pakeerathan T, Knier B, Aly L, Asgari N, Soelberg K, Marignier R, Tilikete CF, Cobo Calvo A, Villoslada P, Sanchez-Dalmau B, Martinez-Lapiscina EH, Llufriu S, Green AJ, Yeaman MR, Smith TJ, Brandt AU, Chen J, Paul F, Havla J; With the GJCF International Clinical Consortium for NMOSD and the CROCTINO Study Group. Longitudinal retinal changes in MOGAD. Ann Neurol. 2022;92:476–485.
Matsunaga Y, Kezuka T, An X, Fujita K, Matsuyama N, Matsuda R, Usui Y, Yamakawa N, Kuroda M, Goto H. Visual functional and histopathological correlation in experimental autoimmune optic neuritis. Invest Ophthalmol Vis Sci. 2012;53:6964–6971.
Castoldi V, Marenna S, d'Isa R, Huang S-C, De Battista D, Chirizzi C, Chaabane L, Kumar D, Boschert U, Comi G, Leocani L. Non-invasive visual evoked potentials to assess optic nerve involvement in the dark agouti rat model of experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein. Brain Pathol. 2020;30:137–150.
Kawachi I. Clinical characteristics of autoimmune optic neuritis. Clin Exp Neuroimmunol. 2017;8:8–16.
Hofman P, Hoyng P, vanderWerf F, Vrensen GF, Schlingemann RO. Lack of blood-brain barrier properties in microvessels of the prelaminar optic nerve head. Invest Ophthalmol Vis Sci. 2001;42:895–901.
Guy J, Rao NA. Acute and chronic experimental optic neuritis. Alteration in the blood-optic nerve barrier. Arch Ophthalmol. 1984;102:450–454.