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Significance of Autoantibodies

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Neuroimmune Diseases

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

Abstract

The field of autoimmune neurological disorders is rapidly expanding, and novel autoantibodies and their neuronal antigens continue to be discovered. Autoimmunity targeting brain proteins is enigmatic, because traditionally, the central nervous system (CNS) is viewed as immune-privileged. However, the discovery of the lymphatic and glymphatic circulation in the CNS demonstrates the interaction between the CNS and the immune response. Furthermore, the barriers protecting the brain from direct exposure to the immune response can be compromised by inflammations, infection, or injury. A compromised blood–brain barrier, or blood–cerebrospinal fluid barrier, will allow egress of neuronal antigens to regional and peripheral lymphoid organs and may lead to the initiation of an autoimmune response. Peripheral autoantibodies or intrathecally produced autoantibodies can reenter the CNS. Besides being useful diagnostic markers, these autoantibodies may be involved in the pathogenesis of the disease by mechanisms such as complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and modulation of receptor function. The effect of a neural autoantibody depends not only on the nature of its antigen but also on the antibody’s Ig isotype or IgG subclass. We will discuss different causes of neurological autoimmunity and pathogenic mechanisms involved in neurological autoimmune diseases. Finally, we will discuss naturally occurring IgM autoantibodies and IgG4 autoantibodies with protective and reparative functions and appropriate treatment options.

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Abbreviations

AChR:

Acetylcholine receptor

ADCC:

Antibody-dependent cell-mediated cytotoxicity

AEBP1:

Adipocyte enhancer-binding protein-1

AMPAR:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic glutamate receptor

AQP4:

Aquaporin-4

ASD:

Autism spectrum disorder

BBB:

Blood–brain barrier

CA:

Cerebellar ataxia caspr: contactin-associated protein 1

CDC:

Complement-dependent cell death

CDR2L:

Cerebellar degeneration-related protein 2-like

CIDP:

Chronic inflammatory demyelinating polyneuropathy

CNS:

Central nervous system

CRMP:

Collapsing response mediator protein

CSF:

Cerebrospinal fluid

GABA:

Gamma-aminobutyric acid

GAD65:

65kda isoform of glutamate decarboxylase

GBS:

Guillain–Barré syndrome

GFAP:

Glial fibrillary acidic protein

hnRNP-A1:

Heterogeneous nuclear ribonuclear protein-A1

HSV-1:

Herpes simplex virus-1

HSVE:

HSV encephalitis

LDH:

Lactate dehydrogenase

LEMS:

Lambert–Eaton myasthenic syndrome

LRP4:

Lipoprotein receptor-related protein 4

MAC:

Membrane attack complex

MAG:

Myelin-associated glycoprotein

MAR:

Maternal autoantibody-related autism

MBP:

Myelin basic protein

MG:

Myasthenia gravis

MOG:

Myelin oligodendrocyte glycoprotein

MS:

Multiple sclerosis

MuSK:

Muscle-specific kinase

MYEOV2:

Myeloma overexpressed gene 2

NMDAR:

N-Methyl-D-aspartate glutamate receptor

NMDARE:

NMDAR encephalitis

NMJ:

Neuromuscular junction

NMO:

Neuromyelitis optica

PCD:

Paraneoplastic degeneration

PEM:

Paraneoplastic encephalomyelitis

PNS:

Paraneoplastic neurologic disorder

PSMD4:

Proteasome non-ATPase regulatory subunit 4

RE:

Rasmussen’s encephalitis

SCI:

Spinal cord injury

SCLC:

Small-cell lung cancer

SGPG:

Sulfoglucuronosyl paragloboside

SLE:

Systemic lupus erythematosus

SPS:

Stiff person syndrome

STIP1:

Stress-induced phosphoprotein 1

SUMPPs:

Small myelin protein-derived peptides

TBI:

Traumatic brain injury

TG:

Transglutaminase

VGCC:

Voltage-gated calcium channel

VGKC:

Voltage-gated potassium channel

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Authors and Affiliations

  1. Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA

    Christiane S. Hampe

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Correspondence to Christiane S. Hampe .

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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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Hampe, C.S. (2019). Significance of Autoantibodies. In: Mitoma, H., Manto, M. (eds) Neuroimmune Diseases. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-030-19515-1_4

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