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Glutamate Receptor Antibodies in Autoimmune Central Nervous System Disease: Basic Mechanisms, Clinical Features, and Antibody Detection

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First Online:
Part of the Methods in Molecular Biology book series (MIMB, volume 1941)

Abstract

Immune-mediated inflammation of the brain has been recognized for more than 50 years, although the initial descriptions were mainly thought to be secondary to an underlying neoplasm. Some of these paraneoplastic encephalitides express serum antibodies, but these were not thought to be pathogenic but instead have a T-cell-mediated pathophysiology. Over the last two decades, several pathogenic antibodies against neuronal surface antigens have been described in autoimmune encephalitis, which are amenable to immunotherapy. Several of these antibodies are directed against glutamate receptors (GluRs). NMDAR encephalitis (NMDARE) is the most common of these antibodies, and patients often present with psychosis, hallucinations, and reduced consciousness. Patients often progress on to develop confusion, seizures, movement disorders, autonomic instability, and respiratory depression. Although initially described as exclusively occurring secondary to ovarian teratoma (and later other tumors), non-paraneoplastic forms are increasingly common, and other triggers like viral infections are now well recognized. AMPAR encephalitis is relatively less common than NMDARE but is more likely to paraneoplastic. AMPAR antibodies typically cause limbic encephalitis, with patients presenting with confusion, disorientation, memory loss, and often seizures. The syndromes associated with the metabotropic receptor antibodies are much rarer and often can be paraneoplastic—mGluR1 (cerebellar degeneration) and mGluR5 (Ophelia syndrome) being the ones described in literature.

With the advance in molecular biology techniques, it is now possible to detect these antibodies using cell-based assays with high sensitivity and specificity, especially when coupled with brain tissue immunohistochemistry and binding to live cell-based neurons. The rapid and reliable identification of these antibodies aids in the timely treatment (either in the form of identifying/removing the underlying tumor or instituting immunomodulatory therapy) and has significantly improved clinical outcome in this otherwise devastating group of conditions.

Key words

Glutamate receptor Autoimmune encephalitis Paraneoplastic Neuronal surface antibodies Neuropsychiatric disorder NMDAR AMPAR mGluR1 mGluR5 KAR Transfected cell-based assay Pathogenic markers 
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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NeurologyUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUK
  2. 2.Department of NeuroimmunologyUniversity of BirminghamBirminghamUK

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