Practical approach for the diagnosis of disorders associated with antibodies against neuronal surface proteins

Since the discovery of a series of antineuronal surface antibodies (NSAs), diagnostic approach to antibody‐mediated encephalitis, and other disorders has undergone a “paradigm shift.” Currently, over ten specific NSAs, whose antigens include synaptic proteins (eg, anti‐N‐methyl‐d‐aspartate receptor) and proteins expressed on the neuronal surface (eg, dipeptidyl‐peptidase‐like protein 6), have been reported. Noble diagnostic implementations that preserve the conformation of the target epitope for NSA detection were developed to optimize the tests' sensitivity and specificity. NSAs can be detected through the following three techniques: tissue‐based assay (TBA) with rodent brain sections, cell‐based assay (CBA), and assays for rodent primary cultured neurons. TBA is a robust screening test that can identify most of the NSAs but cannot confirm specific antibodies. Meanwhile, CBA can confirm the specific antigen of NSAs, thereby suitable for the screening of positive patients. Assays with cultured neurons are also available not only for antibody screening but also for immunoprecipitation to identify an unknown antibody and analyze the antibody effects. Examining the distinctive syndrome caused by NSAs facilitates proper and rapid autoantibody detection, and combining different assays using cerebrospinal fluid minimizes misinterpretation of the tests. The up‐to‐date diagnostic algorithm for NSA‐associated autoimmunity recommends that the diagnostic process of autoantibodies involves screening by TBA/cultured neurons and confirmation by CBA sequentially. Intensive immunosuppressive therapies can be considered when the results of screening assays or confirming tests for NSAs are positive.