Cerebrospinal fluid proteomics indicates immune dysregulation and neuronal dysfunction in antibody associated autoimmune encephalitis

• DOI: 10.1016/j.jaut.2022.102985
• Publication Date: 2023-01-06T17:29:07Z
• Authors: Saskia Räuber; Christina B. Schr...; Christine Strippel; Christopher Nelke; Tillmann Ruland; Andre Dik; Kristin S. Golombeck; Liesa Regner-Nelke; Manuela Paunovic; Daniela Esser; Christian Münch; Felix Rosenow; Martijn van Duijn; Antonia Henes; Tobias Ruck; Ido Amit; Frank Leypoldt; Maarten J. Titulaer; Heinz Wiendl; Sven G. Meuth; Gerd Meyer zu Hörste; Nico Melzer
• Keywords: Autoimmune encephalitis; Immune Dysregulation; Encephalomyelitis; Pathophysiology

Autoimmune Encephalitis (AE) spans a group of non-infectious inflammatory conditions the central nervous system due to an imbalanced immune response. Aiming elucidate pathophysiological mechanisms AE, we applied unsupervised proteomic approach analyze cerebrospinal fluid (CSF) protein profile AE patients with autoantibodies against N-methyl-d-aspartate receptor (NMDAR) (n = 9), leucine-rich glioma-inactivated 1 (LGI1) or glutamate decarboxylase 65 (GAD65) 8) compared 9 relapsing-remitting multiple sclerosis as controls, and 10 somatic symptom disorder non-inflammatory controls. We found dysregulation complement system, disbalance between pro-inflammatory anti-inflammatory proteins on one hand, involved in synaptic transmission, synaptogenesis, brain connectivity, neurodegeneration other hand different extent all subtypes Furthermore, elevated levels several proteases reduction protease inhibitors could be detected Moreover, showed distinct profiles each controls which may facilitate future identification disease-specific biomarkers. Overall, CSF proteomics provides insights into complex including dysregulation, neuronal dysfunction, neurodegeneration, altered function.