Introduction: Autoimmune encephalitis (AIE) is diagnosed through detection of neuronal-surface antibodies (Abs) in serum and/or cerebrospinal fluid (CSF). Commercial biochip-based cell-based assay (CBA) using fixed cells and in-house CBAs using live cells may give incongruent results. We aimed to shed further light on features of AIE patients with discordant CBA results to establish factors related with diagnosis and treatment-response.
Methods: A total of 45 patients found positive for N-methyl-D-aspartate receptor (NMDAR), leucine rich glioma inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2)-Abs on routine screening done with fixed-CBA, were further tested using in-house live-CBA and tissue-based assay (TBA). Serum neurofilament light chain (NFL) levels were measured and response to immunotherapy was assessed in a follow-up period of 36.9±7.8 months.
Results: Thirty patients who were positive on both fixed and live-CBA/TBA, showed trends towards displaying limbic symptoms and EEG/MRI features suggestive of AIE. By contrast, most of the 15 patients with only fixed-CBA positivity failed to fulfill AIE criteria. Positivity on live CBA/TBA did not predict response to immunotherapy or coexisting cancers. Some patients in the fixed-CBA positive category exhibited features highly suggestive of autoimmune encephalopathy and elevated NFL levels. Lower disease severity, presence of viral prodromal findings, absence of autonomic symptoms and facial dyskinesia were associated with treatment response.
Conclusion: Live CBA/TBA demonstrated higher diagnostic accuracy than fixed cell-based assays and substantially reduced the likelihood of false-positive antibody detection. Positive live-CBA/TBA results strongly coincide with definite AIE criteria. However, live CBA and NFL results fail to predict response to immunotherapy and identify coexisting cancers. This is putatively because some patients in the live-CBA/TBA negative category likely have immunotherapy-responsive neuroinflammatory disorders.
Keywords: Autoimmune encephalitis, autoimmunity, cell-based assay, n-methyl-