Significance of Autoantibodies in Autoimmune Encephalitis in Relation to Antigen Localization: An Outline of Frequently Reported Autoantibodies with a Non-Systematic Review

Abstract

Autoantibodies related to central nervous system (CNS) diseases propel research on paraneoplastic neurological syndrome (PNS). This syndrome develops autoantibodies in combination with certain neurological syndromes and cancers, such as anti-HuD antibodies in encephalomyelitis with small cell lung cancer and anti-Yo antibodies in cerebellar degeneration with gynecological cancer. These autoantibodies have roles in the diagnosis of neurological diseases and early detection of cancers that are usually occult. Most of these autoantibodies have no pathogenic roles in neuronal dysfunction directly. Instead, antigen-specific cytotoxic T lymphocytes are thought to have direct roles in neuronal damage. The recent discoveries of autoantibodies against neuronal synaptic receptors/channels produced in patients with autoimmune encephalomyelitis have highlighted insights into our understanding of the variable neurological symptoms in this disease. It has also improved our understanding of intractable epilepsy, atypical psychosis, and some demyelinating diseases that are ameliorated with immune therapies. The production and motility of these antibodies through the blood-brain barrier into the CNS remains unknown. Most of these recently identified autoantibodies bind to neuronal and glial cell surface synaptic receptors, potentially altering the synaptic signaling process. The clinical features differ among pathologies based on antibody targets. The investigation of these antibodies provides a deeper understanding of the background of neurological symptoms in addition to novel insights into their basic neuroscience.

Keywords: autoantibodies; autoimmune encephalitis; cell surface antigen; paraneoplastic; synapse.

Figure 1

Anti-NMDAR antibody-detection using NMDAR GluN1 and GluN2B co-transfected HEK 293 cells. Immunostaining of HEK 293 cells expressing NMDARs in a patient’s CSF and a mixture of rabbit anti-NMDAR antibodies. The same cells were doubly stained with a patient’s CSF and a mixture of rabbit anti-GluN1 and anti-GluN2B antibodies. (A) Staining with CSF from an anti-NMDAR encephalitis patient. AlexaFluor 488-conjugated anti human IgG was used for the secondary antibody (green). (B) Staining with rabbit anti-GluN1 and anti-GluN2B antibody mixture. AlexaFluor 594-conjugated secondary antibody was used (red). (C) Superimposition of the two micrographic images, indicating that the CSF was positive in the anti-NMDAR antibodies. The scale bar in A (10 μm) applies also to B and C.