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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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Experimental autoimmune encephalomyelitis (EAE) with passive transfer of the NMO-IgG, control IgG and vehicle saline control. (A) EAE scores comparing mice receiving NMO-IgG (diamonds, black line) versus vehicle saline control (squares, grey line) with 4 injections on days 13, 14, 18, and 19 as indicated by the black arrows. EAE scores were statistically different starting from day 15 post-immunization. (B) EAE scores comparing mice receiving the NMO-IgG (diamonds, black line) versus control IgG (circles, black line). EAE scores were statistically different starting from day 25 post-immunization. (C) Weight of NMO-IgG mice (diamonds, black line), control IgG mice (circles, dashed line) and vehicle saline control mice (squares, grey line) during course of EAE. Sample size = 10 mice in the NMO group, 9 in the vehicle contorl group, 5 in the control IgG group. Experiment repeated with similar results.
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Figure 1: Experimental autoimmune encephalomyelitis (EAE) with passive transfer of the NMO-IgG, control IgG and vehicle saline control. (A) EAE scores comparing mice receiving NMO-IgG (diamonds, black line) versus vehicle saline control (squares, grey line) with 4 injections on days 13, 14, 18, and 19 as indicated by the black arrows. EAE scores were statistically different starting from day 15 post-immunization. (B) EAE scores comparing mice receiving the NMO-IgG (diamonds, black line) versus control IgG (circles, black line). EAE scores were statistically different starting from day 25 post-immunization. (C) Weight of NMO-IgG mice (diamonds, black line), control IgG mice (circles, dashed line) and vehicle saline control mice (squares, grey line) during course of EAE. Sample size = 10 mice in the NMO group, 9 in the vehicle contorl group, 5 in the control IgG group. Experiment repeated with similar results.

Mentions: Compared to vehicle controls, EAE mice receiving passively transferred NMO-IgG developed significantly worse EAE scores within 24 hours of injection and remained stably worse for 2 months (Figure 1A). EAE mice passively transferred with control-IgG similarly worsened in the first 24 hours but recovered to EAE scores similar to vehicle-treated controls over the next two months (Figure 1B). Exacerbated weight loss persisted in the NMO-IgG-treated mice during the 2-month experiment, thus reflecting the worsening EAE scores during that time period (Figure 1C).


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)

Experimental autoimmune encephalomyelitis (EAE) with passive transfer of the NMO-IgG, control IgG and vehicle saline control. (A) EAE scores comparing mice receiving NMO-IgG (diamonds, black line) versus vehicle saline control (squares, grey line) with 4 injections on days 13, 14, 18, and 19 as indicated by the black arrows. EAE scores were statistically different starting from day 15 post-immunization. (B) EAE scores comparing mice receiving the NMO-IgG (diamonds, black line) versus control IgG (circles, black line). EAE scores were statistically different starting from day 25 post-immunization. (C) Weight of NMO-IgG mice (diamonds, black line), control IgG mice (circles, dashed line) and vehicle saline control mice (squares, grey line) during course of EAE. Sample size = 10 mice in the NMO group, 9 in the vehicle contorl group, 5 in the control IgG group. Experiment repeated with similar results.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Experimental autoimmune encephalomyelitis (EAE) with passive transfer of the NMO-IgG, control IgG and vehicle saline control. (A) EAE scores comparing mice receiving NMO-IgG (diamonds, black line) versus vehicle saline control (squares, grey line) with 4 injections on days 13, 14, 18, and 19 as indicated by the black arrows. EAE scores were statistically different starting from day 15 post-immunization. (B) EAE scores comparing mice receiving the NMO-IgG (diamonds, black line) versus control IgG (circles, black line). EAE scores were statistically different starting from day 25 post-immunization. (C) Weight of NMO-IgG mice (diamonds, black line), control IgG mice (circles, dashed line) and vehicle saline control mice (squares, grey line) during course of EAE. Sample size = 10 mice in the NMO group, 9 in the vehicle contorl group, 5 in the control IgG group. Experiment repeated with similar results.
Mentions: Compared to vehicle controls, EAE mice receiving passively transferred NMO-IgG developed significantly worse EAE scores within 24 hours of injection and remained stably worse for 2 months (Figure 1A). EAE mice passively transferred with control-IgG similarly worsened in the first 24 hours but recovered to EAE scores similar to vehicle-treated controls over the next two months (Figure 1B). Exacerbated weight loss persisted in the NMO-IgG-treated mice during the 2-month experiment, thus reflecting the worsening EAE scores during that time period (Figure 1C).

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