Cerebrospinal fluid biomarker candidates associated with human WNV neuroinvasive disease.
During the last decade, the epidemiology of WNV in humans has changed in the southern regions of Europe, with high incidence of West Nile fever (WNF) cases, but also of West Nile neuroinvasive disease (WNND). The lack of human vaccine or specific treatment against WNV infection imparts a pressing need to characterize indicators associated with neurological involvement. By its intimacy with central nervous system (CNS) structures, modifications in the cerebrospinal fluid (CSF) composition could accurately reflect CNS pathological process. Until now, few studies investigated the association between imbalance of CSF elements and severity of WNV infection. The aim of the present study was to apply the iTRAQ technology in order to identify the CSF proteins whose abundances are modified in patients with WNND. Forty-seven proteins were found modified in the CSF of WNND patients as compared to control groups, and most of them are reported for the first time in the context of WNND. On the basis of their known biological functions, several of these proteins were associated with inflammatory response. Among them, Defensin-1 alpha (DEFA1), a protein reported with anti-viral effects, presented the highest increasing fold-change (FC>12). The augmentation of DEFA1 abundance in patients with WNND was confirmed at the CSF, but also in serum, compared to the control individual groups. Furthermore, the DEFA1 serum level was significantly elevated in WNND patients compared to subjects diagnosed for WNF. The present study provided the first insight into the potential CSF biomarkers associated with WNV neuroinvasion. Further investigation in larger cohorts with kinetic sampling could determine the usefulness of measuring DEFA1 as diagnostic or prognostic biomarker of detrimental WNND evolution.
Aix Marseille Université, Unité de Recherche en Maladies Infectieuses et Tropicales Emergentes, UM63, CNRS 7278, IRD 198, Inserm 1095, Marseille, France; Unité de Recherche en Biologie et Epidémiologie Parasitaires (URBEP), Institut de Recherche Biomédicale des Armées (IRBA), Marseille, France.
Christophe
C
Fraisier
Department of Microbiology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Anna
A
Papa
CRCM, Marseille Protéomique, Inserm, U1068, Marseille, France; Aix-Marseille Université, UM 105, Marseille, France.
Samuel
S
Granjeaud
Department of Neurology, Erasmus MC, Rotterdam, The Netherlands.
Rogier
R
Hintzen
Department of Virology, Erasmus MC, Rotterdam, The Netherlands.
Byron
B
Martina
CRCM, Marseille Protéomique, Inserm, U1068, Marseille, France; Aix-Marseille Université, UM 105, Marseille, France.
Luc
L
Camoin
Aix Marseille Université, Unité de Recherche en Maladies Infectieuses et Tropicales Emergentes, UM63, CNRS 7278, IRD 198, Inserm 1095, Marseille, France; Unité de Recherche en Biologie et Epidémiologie Parasitaires (URBEP), Institut de Recherche Biomédicale des Armées (IRBA), Marseille, France.
Lionel
L
Almeras
D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002493:Central Nervous System Diseases / Q000134:cerebrospinal fluid* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D014901:West Nile Fever / Q000134:cerebrospinal fluid* / Q000473:pathology
D015415:Biomarkers