Introduction: Autoimmune encephalitis (AE) is caused by autoantibodies attacking neuronal cell surface antigens and/or synaptic antigens. We previously demonstrated that S100A6 was hypomethylated in patients with AE and that it promoted B lymphocyte infiltration through the simulated blood-brain barrier (BBB). In this study, we focused on the epigenetic regulation of S100A6, the process by which S100A6 affects B lymphocyte infiltration, and the therapeutic potential of S100A6 antibodies.
Methods: We enrolled and collected serum from 10 patients with AE and 10 healthy control (HC) subjects. Promoter methylation and 5-azacytidine treatment assays were conducted to observe the methylation process of S100A6. The effect of S100A6 on B lymphocytes was analyzed using an adhesion assay and leukocyte transendothelial migration (LTEM) assay. A LTEM assay was also used to compare the effects of the serum of HCs, serum of AE patients, S100A6 recombinant protein, and S100A6 antibodies on B lymphocytes.
Result: The promoter methylation and 5-azacytidine treatment assays confirmed that S100A6 was regulated by DNA methylation. The adhesion study demonstrated that the addition of S100A6 enhanced adhesion between B lymphocytes and a BBB endothelial cell line in a concentration-dependent manner. The LTEM assay showed that the serum of AE patients, as well as S100A6, promoted B lymphocyte infiltration and that this effect could be attenuated by S100A6 antibodies.
Conclusion: We clarified that S100A6 was under epigenetic regulation in patients with AE and that it helped B lymphocytes to adhere to and infiltrate the BBB endothelial layer, which could be counteracted by S100A6 antibodies. Therefore, the methylation profile of S100A6 could be a marker of the activity of AE, and countering the effect of S100A6 may be a potential treatment target for AE.
Keywords: B lymphocyte infiltration; DNA methylation; S100A6; autoimmune encephalitis; leukocyte-endothelial adhesion.
© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.