Plasma metabolomics profiling for the prediction of cytomegalovirus DNAemia and analysis of virus–host interaction in allogeneic stem cell transplant recipients
Metabolomics analysis of biofluids is increasingly being recognized as a useful tool for the diagnosis and management of a number of infectious diseases. Here we showed that plasma metabolomics profiling by untargeted 1H nuclear magnetic resonance may allow the anticipation of the occurrence of cytomegalovirus (CMV) DNAemia in allogeneic stem cell transplant. For this purpose, key discriminatory metabolites were total glutathione, taurine, methylamine, trimethylamine N-oxide and lactate, all of which were upregulated in patients eventually developing CMV DNAemia. The overall classification accuracy (predictability) of the projection to latent structure discriminant analysis (PLS-DA) model in cross-validation technical replicates was 73 %. Increased levels of alanine, lactate and total fatty acids, and a shift in the fatty acid profile towards unsaturated species, were observed in patients with detectable CMV DNA in plasma. The classification accuracy of this PLS-DA model in cross-validation technical replicates was 81 %. Plasma metabolomics profiling may prove useful for identifying patients at highest risk for CMV DNAemia thus allowing early inception of antiviral therapy.
BodiV., SanchisJ., MoralesJ.M., MarrachelliV.G., NuñezJ., FortezaM.J., ChaustreF., GomezC., MainarL., other authors. 2012; Metabolomic profile of human myocardial ischemia by nuclear magnetic resonance spectroscopy of peripheral blood serum: a translational study based on transient coronary occlusion models. J Am Coll Cardiol 59:1629–1641 [View Article][PubMed]
ClariM.Á., BravoD., CostaE., Muñoz-CoboB., SolanoC., RemigiaM.J., GiménezE., Benmarzouk-HidalgoO.J., Pérez-RomeroP., NavarroD.2013; Comparison of the new Abbott Real Time CMV assay and the Abbott CMV PCR Kit for the quantitation of plasma cytomegalovirus DNAemia. Diagn Microbiol Infect Dis 75:207–209 [View Article][PubMed]
GiménezE., Muñoz-CoboB., SolanoC., AmatP., NavarroD., TangY.-W.2014; Early kinetics of plasma cytomegalovirus DNA load in allogeneic stem cell transplant recipients in the era of highly sensitive real-time PCR assays: does it have any clinical value?. J Clin Microbiol 52:654–656 [View Article][PubMed]
HolmesE., LooR.L., StamlerJ., BictashM., YapI.K., ChanQ., EbbelsT., De IorioM., BrownI.J., other authors. 2008; Human metabolic phenotype diversity and its association with diet and blood pressure. Nature 453:396–400 [View Article][PubMed]
LocciE., NotoA., LanariM., LazzarottoT., FanosV., AtzoriL.2013; Metabolomics: a new tool for the investigation of metabolic changes induced by cytomegalovirus. J Matern Fetal Neonatal Med 26:(Suppl. 2)17–19 [View Article][PubMed]
MichaeliB., MartinezA., RevellyJ.P., CayeuxM.C., ChioléroR.L., TappyL., BergerM.M.2012; Effects of endotoxin on lactate metabolism in humans. Crit Care 16:R139 [View Article][PubMed]
MickiewiczB., DugganG.E., WinstonB.W., DoigC., KubesP., VogelH.J., Alberta Sepsis Network. 2014; Metabolic profiling of serum samples by 1H nuclear magnetic resonance spectroscopy as a potential diagnostic approach for septic shock. Crit Care Med 42:1140–1149 [View Article][PubMed]
NotoA., DessiA., PudduM., MussapM., FanosV.2014; Metabolomics technology and their application to the study of the viral infection. J Matern Fetal Neonatal Med 27:(Suppl. 2)53–57 [View Article][PubMed]
TangW.H., WangZ., FanY., LevisonB., HazenJ.E., DonahueL.M., WuY., HazenS.L.2014; Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: refining the gut hypothesis. J Am Coll Cardiol 64:1908–1914 [View Article][PubMed]
TormoN., SolanoC., BenetI., NietoJ., de la CámaraR., LópezJ., Garcia-NoblejasA., Muñoz-CoboB., CostaE., other authors. 2011; Reconstitution of CMV pp65 and IE-1-specific IFN-γ CD8(+) and CD4(+) T-cell responses affording protection from CMV DNAemia following allogeneic hematopoietic SCT. Bone Marrow Transplant 46:1437–1443 [View Article][PubMed]
Plasma metabolomics profiling for the prediction of cytomegalovirus DNAemia and analysis of virus–host interaction in allogeneic stem cell transplant recipients