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Significance of Autoantibodies

  • Christiane S. HampeEmail author
Chapter
Part of the Contemporary Clinical Neuroscience book series (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.

Keywords

Autoantibodies Blood–brain barrier Blood–cerebrospinal fluid barrier Neurological disorders 

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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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of MedicineUniversity of Washington School of MedicineSeattleUSA

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