RNA editing blood biomarkers for predicting mood alterations in HCV patients.
Fiche publication
Date publication
juillet 2019
Journal
Journal of neurovirology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BRONOWICKI Jean-Pierre
Tous les auteurs :
Salvetat N, Van der Laan S, Vire B, Chimienti F, Cleophax S, Bronowicki JP, Doffoel M, Bourlière M, Schwan R, Lang JP, Pujol JF, Weissmann D
Lien Pubmed
Résumé
Treatment-emergent depression is a common complication in patients with chronic hepatitis C virus (HCV) infection undergoing antiviral combination therapy with IFN-α and ribavirin. It has recently been shown that changes in A-to-I RNA editing rates are associated with various pathologies such as inflammatory disorders, depression and suicide. Interestingly, IFN-α induces gene expression of the RNA editing enzyme ADAR1-1 (ADAR1a-p150) and alters overall RNA editing activity. In this study, we took advantage of the high prevalence of pharmacologically induced depression in patients treated with IFN-α and ribavirin to test the interest of RNA editing-related biomarkers in white blood cells of patients. In this 16-week longitudinal study, a small cohort of patients was clinically evaluated using standard assessment methods prior to and during antiviral therapy and blood samples were collected to analyse RNA editing modifications. A-I RNA editing activity on the phosphodiesterase 8A (PDE8A) gene, a previously identified RNA editing hotspot in the context of lupus erythematosus, was quantified by using an ultra-deep next-generation sequencing approach. We also monitored gene expression levels of the ADAR enzymes and the PDE8A gene during treatment by qPCR. As expected, psychiatric evaluation could track treatment-emergent depression, which occurred in 30% of HCV patients. We show that PDE8A RNA editing is increased in all patients following interferon treatment, but differently in 30% of patients. This effect was mimicked in a cellular model using SHSY-5Y neuroblastoma cells. By combining the data of A-I RNA editing and gene expression, we generated an algorithm that allowed discrimination between the group of patients who developed a treatment-emergent depression and those who did not. The current model of drug-induced depression identified A-I RNA editing biomarkers as useful tools for the identification of individuals at risk of developing depression in an objective, quantifiable biological blood test.
Mots clés
A-to-I RNA editing, ADAR, Chronic hepatitis C virus, Depression, Epitranscriptomic biomarkers, Inflammation, Interferon alpha, PDE8A
Référence
J. Neurovirol.. 2019 Jul 22;: