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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

Sections from spinal cords of mice 62 days after injection of NMO-IgG (A, D, G), human IgG controls (B, E, H) and vehicle saline controls (C, F, I). Eriochrome staining shows large areas of pale blue demyelination in the NMO-IgG group (A, magnified in D) as indicated by the arrows. Typical EAE areas of posterior column demyelination were present in the control-IgG (B, magnified in E) and vehicle control (C, magnified in F) groups. Aquaporin-4 staining (red) in all groups were similar and appeared increased in areas of demyelination. Scale bars in D-I represent 100 μm.
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Figure 3: Sections from spinal cords of mice 62 days after injection of NMO-IgG (A, D, G), human IgG controls (B, E, H) and vehicle saline controls (C, F, I). Eriochrome staining shows large areas of pale blue demyelination in the NMO-IgG group (A, magnified in D) as indicated by the arrows. Typical EAE areas of posterior column demyelination were present in the control-IgG (B, magnified in E) and vehicle control (C, magnified in F) groups. Aquaporin-4 staining (red) in all groups were similar and appeared increased in areas of demyelination. Scale bars in D-I represent 100 μm.

Mentions: Sixty-two days after induction of EAE, 43 days following the last IgG infusion, the group that received the NMO-IgG had numerous large subpial demyelinated lesions that were located in the lateral and ventral columns of the spinal cord (Figure 3). Vehicle and control-IgG treated animals had typical demyelinated lesions which extended into the deeper white matter areas, in contrast to NMO-IgG lesions that seemed to be bordered primarily by the pia. Aquaporin-4 staining of these sections revealed homogenous staining but with an increase in AQP4-immunoreactivity in areas of demyelination in all three groups (Figure 3).


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)

Sections from spinal cords of mice 62 days after injection of NMO-IgG (A, D, G), human IgG controls (B, E, H) and vehicle saline controls (C, F, I). Eriochrome staining shows large areas of pale blue demyelination in the NMO-IgG group (A, magnified in D) as indicated by the arrows. Typical EAE areas of posterior column demyelination were present in the control-IgG (B, magnified in E) and vehicle control (C, magnified in F) groups. Aquaporin-4 staining (red) in all groups were similar and appeared increased in areas of demyelination. Scale bars in D-I represent 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Sections from spinal cords of mice 62 days after injection of NMO-IgG (A, D, G), human IgG controls (B, E, H) and vehicle saline controls (C, F, I). Eriochrome staining shows large areas of pale blue demyelination in the NMO-IgG group (A, magnified in D) as indicated by the arrows. Typical EAE areas of posterior column demyelination were present in the control-IgG (B, magnified in E) and vehicle control (C, magnified in F) groups. Aquaporin-4 staining (red) in all groups were similar and appeared increased in areas of demyelination. Scale bars in D-I represent 100 μm.
Mentions: Sixty-two days after induction of EAE, 43 days following the last IgG infusion, the group that received the NMO-IgG had numerous large subpial demyelinated lesions that were located in the lateral and ventral columns of the spinal cord (Figure 3). Vehicle and control-IgG treated animals had typical demyelinated lesions which extended into the deeper white matter areas, in contrast to NMO-IgG lesions that seemed to be bordered primarily by the pia. Aquaporin-4 staining of these sections revealed homogenous staining but with an increase in AQP4-immunoreactivity in areas of demyelination in all three groups (Figure 3).

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