Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis.

@article{Roemer2007PatternspecificLO,
  title={Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis.},
  author={Shanu Faerch Roemer and Joseph E. Parisi and Vanda A. Lennon and Eduardo E. Benarroch and Hans Lassmann and Wolfgang Bruck and Raul N Mandler and Brian G. Weinshenker and Sean J. Pittock and Dean M. Wingerchuk and Claudia F. Lucchinetti},
  journal={Brain : a journal of neurology},
  year={2007},
  volume={130 Pt 5},
  pages={
          1194-205
        }
}
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that typically affects optic nerves and spinal cord. Its pathogenic relationship to multiple sclerosis (MS) is uncertain. Unlike MS, NMO lesions are characterized by deposits of IgG and IgM co-localizing with products of complement activation in a vasculocentric pattern around thickened hyalinized blood vessels, suggesting a pathogenic role for humoral immunity targeting an antigen in the perivascular space. A recently… 

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Mechanisms of Disease: aquaporin-4 antibodies in neuromyelitis optica

An antibody-mediated pathogenesis for NMO is supported by several observations, including the characteristics of the AQP4 antibodies, the distinct NMO pathology—which includes IgG and complement deposition and loss of AQP 4 from spinal cord lesions—and emerging evidence of the beneficial effects of B-cell depletion and plasma exchange.

Loss of aquaporin-4 and GFAP in lesions of neuromyelitis optica: Immunohistochemical study

Pathologically, humoral immunity such as the perivascular deposition of immunoglobulin and complement together with dilated or hyalinized vessels were the dominant immuno-pathological features in the lesions of NMO.

Antibody to aquaporin-4 in the long-term course of neuromyelitis optica

A strong relationship between AQP4-Abs and clinical state is demonstrated, and the hypothesis that these antibodies are involved in the pathogenesis of NMO is supported.

Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica

NMO patients’ serum IgG has a selective pathologic effect on cell membranes expressing aquaporin-4, and targeting astrocytic processes around nodes of Ranvier could initiate demyelination.

Neuromyelitis optica should be classified as an astrocytopathic disease rather than a demyelinating disease

It is proposed that NMO should be classified as an astrocytopathic disease rather than a demyelinating disease because recent experimental studies have convincingly shown that AQP4 antibody is pathogenic in causing astorocytic destruction and dysfunction in vitro, ex vivo and in vivo.

Reappraisal of Aquaporin‐4 Astrocytopathy in Asian Neuromyelitis Optica and Multiple Sclerosis Patients

The present and previous findings suggest that antibody‐independent AQP4 loss can occur in heterogeneous demyelinating conditions, including NMO, Baló's disease and MS.

Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes

Two previously unappreciated histopathological correlates supporting the clinical relevance of the in vitro findings of NMO-IgG are identified: reactive astrocytes with persistent foci of surface AQP4 and vacuolation in adjacent myelin consistent with edema.

Neuromyelitis optica pathogenesis and aquaporin 4

Dysregulation of tolerance associated with autoimmune disease appears to have a role in NMO and reagents and experimental questions that need to be developed and addressed are identified to enhance the understanding of the pathogenesis of NMO.
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