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Passively transferred human NMO-IgG exacerbates demyelination in mouse experimental autoimmune encephalomyelitis.

Saini H, Rifkin R, Gorelik M, Huang H, Ferguson Z, Jones MV, Levy M - BMC Neurol (2013)

Bottom Line: NMO is associated with the highly specific NMO-IgG biomarker, an antibody that binds the aquaporin-4 water channel.In humans, the NMO-IgG portends more frequent exacerbations and a worse long-term clinical outcome.Clinical worsening is associated with an increased concentration of large demyelinating lesions primarily to subpial AQP4-rich regions of the spinal cord.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.

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.

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Related in: MedlinePlus

Optic nerve sections were stained for myelin by eriochrome (blue stain) and AQP4 expression 62 days after injection of human IgG or saline. The mice that received injections of NMO-IgG show areas of pale blue demyelination (arrows in A). The control-IgG group had some demyelination in the optic nerves (arrows in B) and vehicle controls had only few visible demyelinating lesions (panel C). Similar to the spinal cord, AQP4 staining (anti-AQP4, Santa Cruz, white) was increased in all groups in areas of demyelination (sections D-F). Scale bars represent 100 μm.
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Figure 5: Optic nerve sections were stained for myelin by eriochrome (blue stain) and AQP4 expression 62 days after injection of human IgG or saline. The mice that received injections of NMO-IgG show areas of pale blue demyelination (arrows in A). The control-IgG group had some demyelination in the optic nerves (arrows in B) and vehicle controls had only few visible demyelinating lesions (panel C). Similar to the spinal cord, AQP4 staining (anti-AQP4, Santa Cruz, white) was increased in all groups in areas of demyelination (sections D-F). Scale bars represent 100 μm.

Mentions: Similar to the spinal cord, optic nerves from the NMO-IgG-treated group showed subpial demyelinating lesions (Figure 5). The control-IgG and vehicle control groups also had occasional areas of demyelination in the optic nerve and quantitative comparison proved difficult with this small amount of optic nerve tissue. As in the spinal cord, AQP4 staining of optic nerve sections revealed normal homogenous staining of all sections with an increase in staining in areas of demyelination in all three groups (Figure 5).


Passively transferred human NMO-IgG exacerbates demyelination in mouse experimental autoimmune encephalomyelitis.

Saini H, Rifkin R, Gorelik M, Huang H, Ferguson Z, Jones MV, Levy M - BMC Neurol (2013)

Optic nerve sections were stained for myelin by eriochrome (blue stain) and AQP4 expression 62 days after injection of human IgG or saline. The mice that received injections of NMO-IgG show areas of pale blue demyelination (arrows in A). The control-IgG group had some demyelination in the optic nerves (arrows in B) and vehicle controls had only few visible demyelinating lesions (panel C). Similar to the spinal cord, AQP4 staining (anti-AQP4, Santa Cruz, white) was increased in all groups in areas of demyelination (sections D-F). Scale bars represent 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750922&req=5

Figure 5: Optic nerve sections were stained for myelin by eriochrome (blue stain) and AQP4 expression 62 days after injection of human IgG or saline. The mice that received injections of NMO-IgG show areas of pale blue demyelination (arrows in A). The control-IgG group had some demyelination in the optic nerves (arrows in B) and vehicle controls had only few visible demyelinating lesions (panel C). Similar to the spinal cord, AQP4 staining (anti-AQP4, Santa Cruz, white) was increased in all groups in areas of demyelination (sections D-F). Scale bars represent 100 μm.
Mentions: Similar to the spinal cord, optic nerves from the NMO-IgG-treated group showed subpial demyelinating lesions (Figure 5). The control-IgG and vehicle control groups also had occasional areas of demyelination in the optic nerve and quantitative comparison proved difficult with this small amount of optic nerve tissue. As in the spinal cord, AQP4 staining of optic nerve sections revealed normal homogenous staining of all sections with an increase in staining in areas of demyelination in all three groups (Figure 5).

Bottom Line: NMO is associated with the highly specific NMO-IgG biomarker, an antibody that binds the aquaporin-4 water channel.In humans, the NMO-IgG portends more frequent exacerbations and a worse long-term clinical outcome.Clinical worsening is associated with an increased concentration of large demyelinating lesions primarily to subpial AQP4-rich regions of the spinal cord.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.

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.

Show MeSH
Related in: MedlinePlus