title: Myelin oligodendrocyte glycoprotein induces aquaporin-4 autoantibodies in mouse experimental autoimmune encephalomyelitis.
abstract: To investigate whether AQP4 autoantibodies (AQP4-Ab) are causative for neuromyelitis optica (NMO), the production of AQP4-Ab and clinical experimental autoimmune encephalomyelitis (EAE) was investigated in mice administered with mouse AQP4 antigen or myelin oligodendrocyte glycoprotein (MOG35-55) alone, and in combination. Eight- to twelve-week-old female C57BL/6 mice were randomly immunized with encephalitogenic mixture containing 300 μg of MOG35-55 or AQP4 antigen alone, and in combination in complete Freund's adjuvant supplemented with H37Ra M. tuberculosis. The incidence of EAE, Weaver 15 scores, and body weight was evaluated. ELISA was used to detect serum mouse AQP4-Ab. Mice injected with MOG35-55 and MOG33-35 plus AQP4 antigen began to show EAE symptoms 12 days after immunization. The incidence of EAE was 91.6%, and 62.5%, for MOG35-55 alone and MOG33-35 plus AQP4 antigen groups, respectively, while AQP4 antigen alone didn't develop EAE. In all but the control group, serum AQP4-Ab levels were increased, and correlated positively with Weaver 15 score (rs=0.713, p=0.000) and negatively with body weight changes (rs=-0.415, p=0.011). Injection of human NMO sera positive for AQP4-Ab exacerbated MOG-induced EAE. Our results suggest that AQP4-Ab can be produced in MOG-induced MS model, and itself is not sufficient for the development of EAE, implying that NMO might be a subtype or transition from MS.
authors.affiliation: Department of Neurobiology, Key Laboratory of Ministry of Education on Neurodegenerative Diseases, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wu
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.forename: Hui
authors.initials: H
authors.lastname: Ding
authors.forename: Shengli
authors.initials: S
authors.lastname: Xu
authors.forename: Chaodong
authors.initials: C
authors.lastname: Wang
authors.forename: Piu
authors.initials: P
authors.lastname: Chan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051401:Aquaporin 4 / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood* / Q000139:chemically induced / Q000276:immunology; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000235:genetics / Q000502:physiology* / Q000633:toxicity
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D001323:Autoantibodies; D063308:Myelin-Oligodendrocyte Glycoprotein
keywords: Aquaporin-4; Experimental autoimmune encephalomyelitis; Myelin oligodendrocyte glycoprotein; Neuromyelitis optica