Journal
CELLULAR & MOLECULAR IMMUNOLOGY
Volume 18, Issue 2, Pages 294-306Publisher
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/s41423-020-0510-z
Keywords
B cells; Recombinant antibodies; Autoimmunity; Central nervous system; Neurological disorders; Monoclonal; Single cell; Sequencing; Pathogenicity; Epitope; Affinity; B cell tolerance
Categories
Funding
- Australian National Health and Medical Research Council (NHRMC, Australia) [APP1078643, APP1183968]
- Multiple Sclerosis Research Australia
- Sydney Research Excellence Initiative grant (University of Sydney, Australia)
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Autoimmune neurological disorders are characterized by the presence of autoantibodies against neurological antigens, but the characteristics of a single antibody cannot be definitively assigned due to the heterogeneity of patient samples. Single-cell technologies have advanced the understanding of these disorders by revealing abnormalities in tolerance mechanisms and providing insight into B cells responsible for autoantibody production.
Autoimmune neurological disorders, including neuromyelitis optica spectrum disorder, anti-N-methyl-D-aspartate receptor encephalitis, anti-MOG antibody-associated disorders, and myasthenia gravis, are clearly defined by the presence of autoantibodies against neurological antigens. Although these autoantibodies have been heavily studied for their biological activities, given the heterogeneity of polyclonal patient samples, the characteristics of a single antibody cannot be definitively assigned. This review details the findings of polyclonal serum and CSF studies and then explores the advances made by single-cell technologies to the field of antibody-mediated neurological disorders. High-resolution single-cell methods have revealed abnormalities in the tolerance mechanisms of several disorders and provided further insight into the B cells responsible for autoantibody production. Ultimately, several factors, including epitope specificity and binding affinity, finely regulate the pathogenic potential of an autoantibody, and a deeper appreciation of these factors may progress the development of targeted immunotherapies for patients.
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