High-mobility group box-1, promising serological biomarker for the distinction of human WNV disease severity.

The recent increase of West Nile neuroinvasive disease (WNND) incidence in southern Europe made this change in epidemiology a major concern for public health. The lack of a vaccine or specific treatment against human WNV infection imposes the need to discover biological markers associated with disease severity for diagnostic and/or therapeutic purposes. Recently, using a brain proteomic study from a mouse model of West Nile virus (WNV) infection with neuronal involvement, we reported the kinetic up-regulation of high-mobility group box-1 (HMGB1) and peroxiredoxin-6 (PRDX6), before and after onset of clinical symptoms, respectively. To evaluate whether these proteins could be useful biomarkers for the distinction of WNV disease severity in humans, HMBG1 and PRDX6 concentrations in serum from WNV-infected patients (n=49) diagnosed for either WNF (n=22) or WNND (n=27), were measured by ELISA and compared to concentrations in serum from uninfected healthy individuals (n=30). HMGB1 concentrations were significantly higher in WNND than in either WNF patients (p<0.05) or healthy individuals (p<0.001). In contrast, PRDX6 levels were significantly higher in healthy individuals compared with WNV-infected patients (p<0.001), regardless of clinical symptoms. The present study highlighted the deregulation of HMGB1 and PRDX6 serum level in WNV-infected patients and provided HMGB1 as candidate biomarker distinguishing disease severity. Further investigation in larger cohorts could confirm HMGB1 and PRDX6 as auxiliary biomarkers in confirmed cases of WNV infection and validate the usefulness of measuring HMBG1 for prediction of detrimental clinical outcome.