Proteomic Analysis of Cerebrospinal Fluid in Children with Acute Enterovirus-Associated Meningoencephalitis Identifies Dysregulated Host Processes and Potential Biomarkers

Enteroviruses (EVs) are major causes
of viral meningoencephalitis
in children. To better understand the pathogenesis and identify potential
biomarkers, cerebrospinal fluid proteome in children (n = 52) suffering from EV meningoencephalitis was compared to that
in EV-negative control subjects (n = 53) using the
BoxCar acquisition technique. Among 1697 proteins identified, 1193
with robust assay readouts were used for quantitative analyses. Differential
expression analyses identified 154 upregulated and 227 downregulated
proteins in the EV-positive group. Functional analyses showed that
the upregulated proteins are mainly related to activities of lymphocytes
and cytokines, inflammation, and responses to stress and viral invasion,
while the downregulated proteins are mainly related to neuronal integrity
and activity as well as neurogenesis. According to receiver operating
characteristic analysis results, Rho-GDP-dissociation inhibitor 2
exhibited the highest sensitivity (96.2%) and specificity (100%) for
discriminating EV-positive from EV-negative patients. The chemokine
CXCL10 was most upregulated (>300-fold) with also high sensitivity
(92.3%) and specificity (94.3%) for indicating EV positivity. Thus,
this study uncovered perturbations of multiple host processes due
to EV meningoencephalitis, especially the general trend of enhanced
immune responses but impaired neuronal functions. The identified dysregulated
proteins may also prompt biomarker development.