Identification of Cerebrospinal Fluid Metabolites as Biomarkers for Enterovirus Meningitis

International Journal of Molecular Sciences

Frank Pessler¹  Thomas Skripuletz²  Dominica Ratuszny²  Kurt-Wolfram Sühs²  Martin Stangel²  Maike Kuhn³  Natalia Novoselova³  Volkhard Kaever⁴ 

[1] Centre for Individualised Infection Medicine, Feodor-Lynen-Str. 15, 30625 Hannover, Germany;Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany;Institute for Experimental Infection Research, TWINCORE Centre for Experimental and Clinical Infection Research GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany;Research Core Unit Metabolomics, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany;

关键词: enterovirus;    cerebrospinal fluid;    meningitis;    CNS infection;    metabolomics;    biomarker;    phosphatidylcholines;   

DOI  :  10.3390/ijms20020337

来源: DOAJ

【 摘 要 】

Enteroviruses are among the most common causes of viral meningitis. Enteroviral meningitis continues to represent diagnostic challenges, as cerebrospinal fluid (CSF) cell numbers (a well validated diagnostic screening tool) may be normal in up to 15% of patients. We aimed to identify potential CSF biomarkers for enteroviral meningitis, particularly for cases with normal CSF cell count. Using targeted liquid chromatography-mass spectrometry, we determined metabolite profiles from patients with enteroviral meningitis (n = 10), and subdivided them into those with elevated (n = 5) and normal (n = 5) CSF leukocyte counts. Non-inflamed CSF samples from patients with Bell’s palsy and normal pressure hydrocephalus (n = 19) were used as controls. Analysis of 91 metabolites revealed considerable metabolic reprogramming in the meningitis samples. It identified phosphatidylcholine PC.ae.C36.3, asparagine, and glycine as an accurate (AUC, 0.92) combined classifier for enterovirus meningitis overall, and kynurenine as a perfect biomarker for enteroviral meningitis with an increased CSF cell count (AUC, 1.0). Remarkably, PC.ae.C36.3 alone emerged as a single accurate (AUC, 0.87) biomarker for enteroviral meningitis with normal cell count, and a combined classifier comprising PC.ae.C36.3, PC.ae.C36.5, and PC.ae.C38.5 achieved nearly perfect classification (AUC, 0.99). Taken together, this analysis reveals the potential of CSF metabolites as additional diagnostic tools for enteroviral meningitis, and likely other Central nervous system (CNS) infections.

【 授权许可】

Unknown