Elevated Free Phosphatidylcholine Levels in Cerebrospinal Fluid Distinguish Bacterial from Viral CNS Infections
The identification of CSF biomarkers for bacterial meningitis can potentially improve diagnosis and understanding of pathogenesis, and the differentiation from viral CNS infections is of particular clinical importance. Considering that substantial changes in CSF metabolites in CNS infections have re...
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doaj-c7f89e6a9b6c4725ab6081aa9e4395e52021-05-31T23:17:00ZengMDPI AGCells2073-44092021-05-01101115111510.3390/cells10051115Elevated Free Phosphatidylcholine Levels in Cerebrospinal Fluid Distinguish Bacterial from Viral CNS InfectionsAmani Al-Mekhlafi0Kurt-Wolfram Sühs1Sven Schuchardt2Maike Kuhn3Kirsten Müller-Vahl4Corinna Trebst5Thomas Skripuletz6Frank Klawonn7Martin Stangel8Frank Pessler9Biostatistics, Helmholtz Centre for Infection Research, 38124 Braunschweig, GermanyDepartment of Neurology, Clinical Neuroimmunology and Neurochemistry, Hannover Medical School, 30625 Hannover, GermanyFraunhofer Institute for Toxicology and Experimental Medicine (ITEM), 30625 Hannover, GermanyResearch Group Biomarkers for Infectious Diseases, TWINCORE Centre for Experimental and Clinical Infection Research, 30625 Hannover and Helmholtz Centre for Infection Research, 38124 Braunschweig, GermanyDepartment of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, 30625 Hannover, GermanyDepartment of Neurology, Clinical Neuroimmunology and Neurochemistry, Hannover Medical School, 30625 Hannover, GermanyDepartment of Neurology, Clinical Neuroimmunology and Neurochemistry, Hannover Medical School, 30625 Hannover, GermanyBiostatistics, Helmholtz Centre for Infection Research, 38124 Braunschweig, GermanyDepartment of Neurology, Clinical Neuroimmunology and Neurochemistry, Hannover Medical School, 30625 Hannover, GermanyResearch Group Biomarkers for Infectious Diseases, TWINCORE Centre for Experimental and Clinical Infection Research, 30625 Hannover and Helmholtz Centre for Infection Research, 38124 Braunschweig, GermanyThe identification of CSF biomarkers for bacterial meningitis can potentially improve diagnosis and understanding of pathogenesis, and the differentiation from viral CNS infections is of particular clinical importance. Considering that substantial changes in CSF metabolites in CNS infections have recently been demonstrated, we compared concentrations of 188 metabolites in CSF samples from patients with bacterial meningitis (<i>n</i> = 32), viral meningitis/encephalitis (<i>n</i> = 34), and noninflamed controls (<i>n</i> = 66). Metabolite reprogramming in bacterial meningitis was greatest among phosphatidylcholines, and concentrations of all 54 phosphatidylcholines were significantly (<i>p</i> = 1.2 × 10<sup>−25</sup>–1.5 × 10<sup>−4</sup>) higher than in controls. Indeed, all biomarkers for bacterial meningitis vs. viral meningitis/encephalitis with an AUC ≥ 0.86 (ROC curve analysis) were phosphatidylcholines. Four of the five most accurate (AUC ≥ 0.9) phosphatidylcholine biomarkers had higher sensitivity and negative predictive values than CSF lactate or cell count. Concentrations of the 10 most accurate phosphatidylcholine biomarkers were lower in meningitis due to opportunistic pathogens than in meningitis due to typical meningitis pathogens, and they correlated most strongly with parameters reflecting blood–CSF barrier dysfunction and CSF lactate (<i>r</i> = 0.73–0.82), less so with CSF cell count, and not with blood CRP. In contrast to the elevated phosphatidylcholine concentrations in CSF, serum concentrations remained relatively unchanged. Taken together, these results suggest that increased free CSF phosphatidylcholines are sensitive biomarkers for bacterial meningitis and do not merely reflect inflammation but are associated with local disease and a shift in CNS metabolism.https://www.mdpi.com/2073-4409/10/5/1115biomarkercentral nervous systemcell membraneenterovirusherpes simplex virusinfection |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Amani Al-Mekhlafi Kurt-Wolfram Sühs Sven Schuchardt Maike Kuhn Kirsten Müller-Vahl Corinna Trebst Thomas Skripuletz Frank Klawonn Martin Stangel Frank Pessler |
spellingShingle |
Amani Al-Mekhlafi Kurt-Wolfram Sühs Sven Schuchardt Maike Kuhn Kirsten Müller-Vahl Corinna Trebst Thomas Skripuletz Frank Klawonn Martin Stangel Frank Pessler Elevated Free Phosphatidylcholine Levels in Cerebrospinal Fluid Distinguish Bacterial from Viral CNS Infections Cells biomarker central nervous system cell membrane enterovirus herpes simplex virus infection |
author_facet |
Amani Al-Mekhlafi Kurt-Wolfram Sühs Sven Schuchardt Maike Kuhn Kirsten Müller-Vahl Corinna Trebst Thomas Skripuletz Frank Klawonn Martin Stangel Frank Pessler |
author_sort |
Amani Al-Mekhlafi |
title |
Elevated Free Phosphatidylcholine Levels in Cerebrospinal Fluid Distinguish Bacterial from Viral CNS Infections |
title_short |
Elevated Free Phosphatidylcholine Levels in Cerebrospinal Fluid Distinguish Bacterial from Viral CNS Infections |
title_full |
Elevated Free Phosphatidylcholine Levels in Cerebrospinal Fluid Distinguish Bacterial from Viral CNS Infections |
title_fullStr |
Elevated Free Phosphatidylcholine Levels in Cerebrospinal Fluid Distinguish Bacterial from Viral CNS Infections |
title_full_unstemmed |
Elevated Free Phosphatidylcholine Levels in Cerebrospinal Fluid Distinguish Bacterial from Viral CNS Infections |
title_sort |
elevated free phosphatidylcholine levels in cerebrospinal fluid distinguish bacterial from viral cns infections |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2021-05-01 |
description |
The identification of CSF biomarkers for bacterial meningitis can potentially improve diagnosis and understanding of pathogenesis, and the differentiation from viral CNS infections is of particular clinical importance. Considering that substantial changes in CSF metabolites in CNS infections have recently been demonstrated, we compared concentrations of 188 metabolites in CSF samples from patients with bacterial meningitis (<i>n</i> = 32), viral meningitis/encephalitis (<i>n</i> = 34), and noninflamed controls (<i>n</i> = 66). Metabolite reprogramming in bacterial meningitis was greatest among phosphatidylcholines, and concentrations of all 54 phosphatidylcholines were significantly (<i>p</i> = 1.2 × 10<sup>−25</sup>–1.5 × 10<sup>−4</sup>) higher than in controls. Indeed, all biomarkers for bacterial meningitis vs. viral meningitis/encephalitis with an AUC ≥ 0.86 (ROC curve analysis) were phosphatidylcholines. Four of the five most accurate (AUC ≥ 0.9) phosphatidylcholine biomarkers had higher sensitivity and negative predictive values than CSF lactate or cell count. Concentrations of the 10 most accurate phosphatidylcholine biomarkers were lower in meningitis due to opportunistic pathogens than in meningitis due to typical meningitis pathogens, and they correlated most strongly with parameters reflecting blood–CSF barrier dysfunction and CSF lactate (<i>r</i> = 0.73–0.82), less so with CSF cell count, and not with blood CRP. In contrast to the elevated phosphatidylcholine concentrations in CSF, serum concentrations remained relatively unchanged. Taken together, these results suggest that increased free CSF phosphatidylcholines are sensitive biomarkers for bacterial meningitis and do not merely reflect inflammation but are associated with local disease and a shift in CNS metabolism. |
topic |
biomarker central nervous system cell membrane enterovirus herpes simplex virus infection |
url |
https://www.mdpi.com/2073-4409/10/5/1115 |
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