Passively transferred human NMO-IgG exacerbates demyelination in mouse experimental autoimmune encephalomyelitis.
BACKGROUND
Neuromyelitis optica (NMO) is a devastating inflammatory disorder of the optic nerves and spinal cord characterized by frequently recurring exacerbations of humoral inflammation. NMO is associated with the highly specific NMO-IgG biomarker, an antibody that binds the aquaporin-4 water channel. Aquaporin-4 is present on glial endfeet in the central nervous system (CNS). In humans, the NMO-IgG portends more frequent exacerbations and a worse long-term clinical outcome.


METHODS
We tested the longer-term outcome of mice with EAE injected with NMO-IgG and followed them for 60 days. Clinical exams and pathology of the spinal cord and optic nerves were compared to mice that received control human IgG.


RESULTS
Passively transferred human NMO-IgG leads to more severe neurology disability over two months after onset of disease. Clinical worsening is associated with an increased concentration of large demyelinating lesions primarily to subpial AQP4-rich regions of the spinal cord.


CONCLUSIONS
NMO-IgG is pathogenic in the context of EAE in mice.
Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Harleen
H
Saini
Robert
R
Rifkin
Michael
M
Gorelik
Hwa
H
Huang
Zachary
Z
Ferguson
Melina V
MV
Jones
Michael
M
Levy
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000950:Antigens, Ly / Q000276:immunology / Q000378:metabolism; D051401:Aquaporin 4 / Q000276:immunology / Q000378:metabolism; D003711:Demyelinating Diseases / Q000150:complications / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood* / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D009471:Neuromyelitis Optica / Q000276:immunology*; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000633:toxicity; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D015703:Antigens, CD; D000950:Antigens, Ly; D051401:Aquaporin 4; D007074:Immunoglobulin G; C480309:Ly6G antigen, mouse; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)