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Autoimmune Astrocytopathy

  • Jorge CorrealeEmail author
  • María I. Gaitán
Chapter
Part of the Contemporary Clinical Neuroscience book series (CCNE)

Abstract

Astrocytes are the most abundant and heterogeneous type of glial cell in the Central Nervous System. In addition to their role maintaining physiological conditions stable in the CNS, they are recognized as early and highly active players in immune responses in the CNS, and their dysfunction is believed to contribute to neuroimmune disease.

Perhaps one of the most important discoveries in recent years has been the identification of IgG-NMO, a specific pathogenic antibody directed against water channel aquaporin-4 (AQP4). IgG-NMO has not only made neuromyelitis optica diagnosis easier but has allowed differential diagnoses to be established more clearly and lead to the design of better therapeutic alternatives. Likewise, a novel autoantibody directed against GFAP has been identified as biomarker of a relapsing autoimmune form of meningoencephalomyelitis, responsive to steroids, often associated with tumors. Similarly, in Rasmussen’s encephalitis, CD8+ T lymphocytes cause astrocyte apoptosis and loss in affected areas, altering normal neuron function. Reactive astrocytes also play an important role in different CNS infections, not only during acute phases of disease but also long term, and may condition the development of post-infectious sequelae. Finally, multiple mechanisms mediated by astrocytes are known to participate in both the genesis and the progression of MS and in processes of remyelination. Overall, these observations indicate astrocytes actively participate in both pathological and in repair mechanisms, observed in CNS neuroimmune diseases.

Keywords

Anti-AQP4 Anti-GFAP Astrocytes Multiple sclerosis Neuromyelitis optica Rasmussen’s encephalitis 

Abbreviations

AMPA

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

AQP4

Aquaporin 4

ATP

Adenosine triphosphate

B4GALT5

4-Galactosyltransferase 5

BAFF

B-cell activating factor

BBB

Blood–brain barrier

C1q

Complement component subunit 1q

CNS

Central Nervous System

CNTF

Ciliary neurotrophic factor

CSPGs

Chondroitin sulfate proteoglycans

Cx

Connexin

DAMPS

Danger-associated molecules patterns

EAAT2

Excitatory amino acid transporter 2

EAE

Experimental autoimmune encephalomyelitis

ECM

Extracellular matrix

EPH

Ephrins

Fas-L

Fas ligand

FGF

Fibroblast growth factor

FoxP3

Forkhead box P3

GAG

Glycosaminoglycan

GFAP

Glial fibrillary acidic protein

GLAST

Glutamate/aspartate transporter

GLT-1

Glutamate transporter-1

GluR3

Glutamate receptor 3

GM-CSF

Granulocyte macrophage colony-stimulating factor

GS

Glutamine synthetase

HMGB1

High-mobility box-1

ICAM 1

Intercellular adhesion molecule 1

IFNs

Interferons

iNOS

Inducible nitric oxide synthase

IRF-1

Interferon regulatory factor 1

ISGs

Interferon-stimulated genes

LacCer

Lactosylceramide

LFA-1

Lymphocyte function-associated antigen

LIF

Leukemia inhibitory factor

LPS

Lipopolysaccharide

M-CSF

Macrophage colony-stimulating factor

MMPs

Matrix metalloproteinases

NF-κB

Nuclear factor kappa-light-chain-enhancer of activated B cells

NG2

Neuron-glial antigen 2

NMDA

N-methyl-D-aspartate

NMO

Neuromyelitis optica

NMOSD

Neuromyelitis optica spectrum disorders

NO

Nitric oxide

ONOO

Peroxinitrate

OPCs

Oligodendrocyte progenitor cells

PAMPs

Pathogen-associated molecular patterns

PRRs

Pattern recognition receptors

RAGE

Receptor for advanced glycation end products

RE

Rasmussen’s encephalitis

RLRs

Retinoic acid-inducible gene-like receptors

S100β

S100 calcium-binding protein

TGF

Transforming growth factor

Th

T helper cell

Tim-3

T cell immunoglobulin and mucin domain 3

TIMPs

Tissue inhibitors of metalloproteinases

TLR

Toll-like receptor

Tr1

Type 1 regulatory T cells

VCAM-1

Vascular cell adhesion protein 1

VLA-4

Very late antigen 4

Notes

Acknowledgments

This work was supported by an unrestricted grant from FLENI.

The authors thank Dr. Ismael Calandri for preparation of some figures.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of NeurologyFLENIBuenos AiresArgentina

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