Autoantibodies in neurological disease

Abstract

The realization that autoantibodies can contribute to dysfunction of the brain has brought about a paradigm shift in neurological diseases over the past decade, offering up important novel diagnostic and therapeutic opportunities. Detection of specific autoantibodies to neuronal or glial targets has resulted in a better understanding of central nervous system autoimmunity and in the reclassification of some diseases previously thought to result from infectious, ‘idiopathic’ or psychogenic causes. The most prominent examples, such as aquaporin 4 autoantibodies in neuromyelitis optica or NMDAR autoantibodies in encephalitis, have stimulated an entire field of clinical and experimental studies on disease mechanisms and immunological abnormalities. Also, these findings inspired the search for additional autoantibodies, which has been very successful to date and has not yet reached its peak. This Review summarizes this rapid development at a point in time where preclinical studies have started delivering fundamental new data for mechanistic understanding, where new technologies are being introduced into this field, and — most importantly — where the first specifically tailored immunotherapeutic approaches are emerging.

Clinical and Imaging Features of Patients With Encephalitic Symptoms and Myelin Oligodendrocyte Glycoprotein Antibodies

“…They block the interaction of LGI1 with its receptors to disrupt protein-protein interaction, but they do not activate complement or cause damage to neurons. However, MOG-ab target the myelin sheath of axons and induce FcRmediated antibody-dependent cellular cytotoxicity (33). As cognitive/psychiatric impairment mediated by different antibodies showed different prognosis, it is significant to differentiate them as early as possible.…”

Next Generation Sequencing of Cerebrospinal Fluid B Cell Repertoires in Multiple Sclerosis and Other Neuro-Inflammatory Diseases—A Comprehensive Review

“…Concerning other autoantibody-mediated encephalopathies, numerous antibodies targeting neuronal or glial cells have recently been described in neurological diseases. In this context, the anti-N-methyl-d-aspartate receptor (NMDAR) and leucine-rich, gliomainactivated 1 (LGI1) autoantibody-mediated encephalitis is one of the best-characterized disease entities [27]. Although CSF LGI1 antibodies are detected in around 90% of patients, there is an infrequent association with CSF lymphocytosis and OCB in LGI1 encephalitis [28,29].…”

“…From a clinical perspective, patients with autoantibody-mediated encephalitis often present with new-onset psychosis, amnesia, hyperkinesia or vegetative dysfunction. With the discovery of anti-neuronal antibodies, these patients now receive causal therapies, including B cell depletion and antibody removal, instead of solely symptomatic treatments [27].…”

Stem cells part of the innate and adaptive immune systems as a therapeutic for Covid-19

“…Likewise, Covid-19 vaccines have been found to elicit damaging autoantibodies, requiring in some cases the need for life-saving, drastic therapeutic intervention, including plasma exchange, corticosteroids, rituximab to destroy a subset of B cells [but, importantly, not gut B cells that quell inflammation in autoimmune disorders; see 102], and Caplacizumab to break the abnormal blood clotting [103]. Autoantibody production can be a longterm event, and lead to numerous physical ills, including neurodegenerative diseases [104]. Mesenchymal stem cells have been shown to limit B cell mediated autoimmunity [105] and reduce autoantibody levels in serum [106], and along with diet [107,108] may be an important therapeutic strategy in limiting autoantibody production and autoimmune diseases, often a part of the Covid-19 sequalae.…”