Sanja Stopinšek, Saša Simčič
Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Slovenia
Autoimmune encephalitis (AE) is an immune-mediated disease with diverse neurological symptoms. The discovery that several forms of encephalitis results from antibodies against neuronal cell antigens has led to a paradigm shift in diagnostic approach of encephalitis. AE has been associated with antibodies against intracellular neuronal antigens Hu, Ma2, Ri, CV2, amphyphisin and GAD. These antibodies occur in middle-aged or elderly patients sometimes with previous history of cancer. They do not appear to be directly pathogenic but can be very useful as a marker of disease. Because of irreversible cytotoxic neuronal damage, these patients do not respond well to immunotherapy. A rapidly expanding subset of AE occurs in association with antibodies to neuronal cell-surface or synaptic antigens like NMDAR, AMPAR, GABABR, LGI1, CASPR, DPPX and mGluR5. These antibodies occur in patients of all ages and are less commonly associated with cancer. They can be pathogenic by disrupting t he function of the target protein. The neurological symptoms may be reversible and respond well to immunotherapy. Laboratory tests for intracellular antigens frequently involve immunohistochemistry on tissue arrays and immunoblotting of proteins, while antibodies against neuronal cell-surface proteins are determined by cell-based assays with transfected cells expressing the antigen of interest. AE can resemble infectious encephalitis and comprises an expanding group of potentially treatable disorders that should be in the differential diagnosis of any type of encephalitis. A comprehensive analysis of clinical evaluation and determination of autoantibodies in patient’s serum and/or cerebrospinal fluid is necessary to confirm the diagnosis of AE.
Keywords: autoimmune encephalitis, neuronal surface antibodies, paraneoplatic antibodies