Temporal dynamics of the cerebrospinal fluid proteome in tick-borne encephalitis and enteroviral meningitis

Background Tick-borne encephalitis (TBE) is a severe viral infection of the central nervous system (CNS), causing acute meningoencephalitis and often long-term neurocognitive sequelae. The lack of specific treatment for TBE highlights the need to improve understanding of disease mechanisms and identify novel biomarkers. Enteroviral meningitis is typically a milder infection of the CNS and rarely causes encephalitis.Objectives In this hypothesis-generating study, we aimed to characterise temporal changes in the cerebrospinal fluid (CSF) proteome in TBE and identify candidate biomarkers associated with pathophysiological mechanisms, disease severity, and neurocognitive outcome.Methods Patients with TBE, enteroviral meningitis, or aseptic meningoencephalitis of unknown origin were retrospectively included from a previously established cohort. CSF proteomes were analysed by label-free mass spectrometry, followed by differential protein expression analysis and functional annotation. Temporal proteome dynamics and protein associations with disease severity and neurocognitive outcome were assessed. Data are available via ProteomeXchange with identifier PXD077931.Results Proteomic analyses revealed alterations in proteins related to synaptic function, inflammatory pathways, the complement system, and the 14-3-3 protein family. Adrenomedullin was markedly increased in the late phase of TBE compared with enteroviral meningitis.Conclusion Temporal changes in the CSF proteome in TBE indicate a strong inflammatory response occurring in concert with lower levels of proteins related to synaptic function during the acute phase. These findings provide insights into the host response and pathogenesis of TBE and identify proteins of potential interest for future validation.