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Topic: Autoimmune neurological diseases associated with
autoantibodies specific for synaptic antigens

Encephalitis associated with autoantibodies binding

to γ‑aminobutyric acid‑A, γ‑aminobutyric acid‑B and

glycine receptors: immunopathogenic mechanisms

and clinical characteristics

Amy May Lin Quek , Orna O’Toole 3
1,2
1 Department of Medicine, National University Hospital, National University Health System, Singapore 119228, Singapore.
2 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
3 Department of Neurology, Mercy University Hospital, Grenville Place, Cork, Ireland.

A B S T R AC T
Recent, discoveries of neural antibodies have facilitated the diagnosis of immune‑mediated, immunotherapy‑responsive neurologic
disorders. Antibodies that target inhibitory central nervous system receptors, such as γ‑aminobutyric acid‑B, γ‑aminobutyric
acid‑A, and glycine receptors, disrupt inhibitory regulatory synaptic functions, and lead to neuronal hyperexcitability. The myriad
of neurologic, manifestations associated with these antibodies includes seizures, encephalopathy, muscle rigidity and stiffness.
This article provides a review of the immunopathogenic mechanisms and the clinical and therapeutic implications of autoimmune
encephalitis associated with these antibodies that target inhibitory receptors.
Key words: Autoimmune encephalitis; autoimmune epilepsy; limbic encephalitis; neural antibodies

INTRODUCTION mirror genetic and pharmacologically induced disorders
of the target receptors. In this review, we describe
[8]
Recent, discoveries of neural antibodies that bind to the immunopathogenic mechanisms of autoimmune
antigenic targets in the brain have led to a paradigm encephalitis associated with antibodies targeting the
shift in the clinical approach to patients presenting with inhibitory synaptic receptors γ‑aminobutyric acid‑B
encephalopathy, [1‑4] cognitive change, and refractory (GABA ), γ‑aminobutyric acid‑A (GABA ), and glycine
[5]
B
A
seizures. [4,6] With a wider availability of neural antibody receptors (GlyRs), together with their clinical and
testing, a significant proportion of the patients, who were therapeutic implications.
previously diagnosed with encephalitis of undetermined
etiology have been shown to have neurologic symptoms ANTI‑GABA RECEPTOR AND ANTI‑GABA
B
A
caused by an underlying autoimmune disorder and some RECEPTOR ENCEPHALITIS
of these patients respond favorably to immunosuppressive GABA, the main inhibitory neurotransmitter in the brain,
[7]
treatments. Neural antibodies that, target channels or binds to metabotropic and ionotropic receptors to regulate
receptors on the neuronal cell surface can interfere with neuronal activity. To date, GABA receptor (GABA R)
B
B
the function of these proteins, leading to altered neuronal and GABA receptor (GABA R) have been identified as
A
A
excitability, and a myriad of neurologic syndromes that antigenic targets of autoimmunity [Table 1].
Corresponding Author: Dr. Amy May Lin Quek, Department Anti‑GABA R encephalitis
of Medicine, National University Hospital, National University B
Health System, National University Hospital Tower Block, 1E The GABA R is a metabotropic G‑protein‑coupled
B
Kent Ridge Road, Singapore 119228, Singapore.
E‑mail: amy_quek@nuhs.edu.sg This is an open access article distributed under the terms of the Creative
Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non‑commercially, as long as the
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author is credited and the new creations are licensed under the identical terms.
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Cite this article as: Quek AML, O'Toole O. Encephalitis associated with
autoantibodies binding to γ‑aminobutyric acid‑A, γ‑aminobutyric acid‑B
and glycine receptors: immunopathogenic mechanisms and clinical
DOI: characteristics.Neuroimmunol Neuroinflammation 2016;3:86-92.
10.4103/2347-8659.170633
Received: 27-01-2015; Accepted: 22-07-2015

86 © 2016 Neuroimmunology and Neuroinflammation | Published by OAE Publishing Inc.