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Kynurenine is a cerebrospinal fluid biomarker for bacterial and viral CNS infections.
Sühs, Kurt-Wolfram Novoselova, Natalia Kuhn, Maike Seegers, Lena Kaever, Volkhard Müller-Vahl, Kirsten Trebst, Corinna Skripuletz, Thomas Stangel, Martin Pessler, Frank
Sühs, Kurt-Wolfram
Novoselova, Natalia
Kuhn, Maike
Seegers, Lena
Kaever, Volkhard
Müller-Vahl, Kirsten
Trebst, Corinna
Skripuletz, Thomas
Stangel, Martin
Pessler, Frank
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2019-02-05
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Abstract
The tryptophan-kynurenine-NAD+ pathway is closely associated with regulation of immune cells toward less inflammatory phenotypes and may exert neuroprotective effects. Investigating its regulation in CNS infections would improve our understanding of pathophysiology and end-organ damage, and, furthermore, open doors to its evaluation as a source of diagnostic and/or prognostic biomarkers. We measured concentrations of kynurenine (Kyn) and tryptophan (Trp) in 220 cerebrospinal fluid samples from patients with bacterial and viral (herpes simplex, varicella zoster, enteroviruses) meningitis/encephalitis, neuroborreliosis, autoimmune neuroinflammation (anti-NMDA-R encephalitis, multiple sclerosis), and noninflamed controls (Bell's palsy, normal pressure hydrocephalus, Tourette syndrome). Kyn concentrations correlated strongly with CSF markers of neuroinflammation (leukocyte count, lactate, and blood-CSF-barrier dysfunction) and were highly increased in bacterial and viral CNS infections, but were low or undetectable in anti-NMDA-R encephalitis, multiple sclerosis, and controls. Trp was decreased mostly in viral CNS infections and neuroborreliosis. Multiple logistic regression analysis revealed combinations of Kyn, Trp and Kyn/Trp ratio with leukocyte count or lactate as accurate classifiers for the clinically important differentiation between neuroborreliosis, viral CNS infections, and autoimmune neuroinflammation. The Trp-Kyn-NAD+ pathway is activated in CNS infections and provides highly accurate CSF biomarkers, particularly when combined with standard CSF indices of neuroinflammation.
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J Infect Dis. 2019 Feb 5. pii: 5307059. doi: 10.1093/infdis/jiz048.
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en
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1537-6613
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Attribution-NonCommercial-ShareAlike 4.0 International