Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antigens, CD / immunology
-
Antigens, CD / metabolism
-
Antigens, Ly / immunology
-
Antigens, Ly / metabolism
-
Aquaporin 4 / immunology
-
Aquaporin 4 / metabolism
-
Demyelinating Diseases / complications
-
Demyelinating Diseases / immunology
-
Disease Models, Animal
-
Encephalomyelitis, Autoimmune, Experimental / blood*
-
Encephalomyelitis, Autoimmune, Experimental / etiology
-
Encephalomyelitis, Autoimmune, Experimental / immunology*
-
Encephalomyelitis, Autoimmune, Experimental / pathology
-
Female
-
Humans
-
Immunoglobulin G / blood*
-
Mice
-
Mice, Inbred C57BL
-
Myelin Sheath / metabolism
-
Myelin Sheath / pathology
-
Myelin-Oligodendrocyte Glycoprotein / toxicity
-
Neuromyelitis Optica / immunology*
-
Optic Nerve / metabolism
-
Optic Nerve / pathology
-
Peptide Fragments / toxicity
-
Spinal Cord / metabolism
-
Spinal Cord / pathology
-
Time Factors
Substances
-
Antigens, CD
-
Antigens, Ly
-
Aquaporin 4
-
Immunoglobulin G
-
Ly6G antigen, mouse
-
Myelin-Oligodendrocyte Glycoprotein
-
Peptide Fragments
-
myelin oligodendrocyte glycoprotein (35-55)