Differences in innate immune cell populations distinguish autoimmune from herpesvirus-associated encephalitis

• DOI: 10.1016/j.jaut.2025.103396
• Publication Date: 2025-03-04T07:40:21Z
• Authors: Saskia Räuber; Andreas Schulte-M...; Kelvin Sarink; Kristin S. Golombeck; Christina B. Schr...; Alice Willison; Christopher Nelke; Christine Strippel; Andre Dik; Marco Gallus; Stjepana Kovac; Heinz Wiendl; Gerd Meyer zu Hörste; Tobias Ruck; Oliver M. Grauer; Udo Dannlowski; Tim Hahn; Catharina C. Gross; Sven G. Meuth; Nico Melzer
• Keywords: Autoimmune encephalitis; Innate lymphoid cell

Autoimmune encephalitis (AIE) is a disabling inflammatory condition of the brain deemed to be due dysregulated immune response. Viral infections and malignancies together with certain genetic polymorphisms are thought contribute pathogenesis AIE, yet exact mechanisms remain insufficiently understood. Diagnosis AIE currently relies on clinical consensus criteria. However, diagnostic workup can challenging in some cases, potentially delaying treatment initiation associated poor outcomes. This study aims investigate systemic intrathecal cell profiles comparison viral meningoencephalitis (VME) as clinically relevant differential diagnosis evaluate its therapeutic potential. 97 mainly treatment-naïve patients, 47 patients VME, 109 somatic symptom disorder (SD) controls were included. Analysis peripheral blood (PB) cerebrospinal fluid (CSF) was performed using multidimensional flow cytometry (mFC) combination novel computational approaches. We able identify alterations adaptive B T cell-mediated response compared SD which correspond respective changes parenchyma. VME exhibit similar patterns responses differ pattern innate immunity especially NK cells. MFC routine CSF parameters differentiate from implying characterized by immune-cell signature corresponds reported parenchyma providing insights into immunopathogenesis. Differences between most prominent for indicating potential role cells autoimmunity. Our data provides evidence that mFC could complementary approach diagnostic, therapeutic, prognostic implications.