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Autoimmune Astrocytopathy

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Book cover Neuroimmune Diseases

Part of the book series: Contemporary Clinical Neuroscience ((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.

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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

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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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Authors and Affiliations

  1. Department of Neurology, FLENI, Buenos Aires, Argentina

    Jorge Correale & María I. Gaitán

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  1. Jorge Correale
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  2. María I. Gaitán
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Correspondence to Jorge Correale .

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  1. Medical Education Promotion Center, Tokyo Medical University, Tokyo, Japan

    Hiroshi Mitoma

  2. Department of Neurology, CHU-Charleroi, Charleroi, Belgium, Department of Neurosciences, University of Mons, Mons, Belgium

    Mario Manto

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Correale, J., Gaitán, M.I. (2019). Autoimmune Astrocytopathy. In: Mitoma, H., Manto, M. (eds) Neuroimmune Diseases. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-030-19515-1_10

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