Plaatjie Ontefetse Neo, van Furth A Marceline Tutu, Solomons Regan, van der Kuip Martijn, Mason Shayne
Department of Biochemistry, Human Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom, South Africa.
Department of Paediatric Infectious Diseases and Immunology, Amsterdam University Medical Center, Emma Children's Hospital, Amsterdam, The Netherlands.
Sci Rep. 2025 Aug 11;15(1):29366. doi: 10.1038/s41598-025-15000-0.
The poor outcome of tuberculous meningitis (TBM) is largely due to the difficulty of diagnosis caused by nonspecific symptoms and the absence of specific and sensitive tests. Carnitines regulate energy metabolism, and their elevation has been consistently reported in the cerebrospinal fluid (CSF) of TBM patients. We employed a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach to investigate the acylcarnitine metabolome in paediatric TBM, comparing it to non-meningitis controls (NMC) and viral meningitis (VM). We also investigated correlations of significant acylcarnitines with clinical metadata. We found that short-chain acylcarnitines were significantly elevated in TBM. Acetylcarnitine, propionylcarnitine, and butyrylcarnitine demonstrated significant diagnostic potential in distinguishing between TBM and control groups, with 80-90% specificity and 70-80% sensitivity. Free carnitine stood out as the strongest potential marker for TBM, distinguishing TBM from NMC (100% specificity, 90% sensitivity) and VM (80% specificity, 90% sensitivity). Furthermore, free carnitine is strongly correlated with basal meningeal enhancement and hydrocephalus, key neuroradiological markers of TBM. Free carnitine could serve as a potential biomarker for TBM, as well as a marker of TBM severity. Our results suggest that disruptions in fatty acid and energy metabolism in TBM cases are important because free carnitine plays a crucial role in the β-oxidation of fatty acids by transporting long-chain fatty acids into the mitochondria for energy production.
结核性脑膜炎（TBM）预后不佳很大程度上是由于非特异性症状导致诊断困难，且缺乏特异性和敏感性高的检测方法。肉碱调节能量代谢，TBM患者脑脊液（CSF）中肉碱水平持续升高已有报道。我们采用靶向液相色谱-串联质谱（LC-MS/MS）方法研究儿童TBM的酰基肉碱代谢组，并与非脑膜炎对照组（NMC）和病毒性脑膜炎（VM）进行比较。我们还研究了显著酰基肉碱与临床元数据之间的相关性。我们发现TBM中短链酰基肉碱显著升高。乙酰肉碱、丙酰肉碱和丁酰肉碱在区分TBM和对照组方面具有显著的诊断潜力，特异性为80-90%，敏感性为70-80%。游离肉碱是TBM最有力的潜在标志物，可将TBM与NMC（特异性100%，敏感性90%）和VM（特异性80%，敏感性90%）区分开来。此外，游离肉碱与基底脑膜强化和脑积水密切相关，这是TBM的关键神经放射学标志物。游离肉碱可作为TBM的潜在生物标志物，以及TBM严重程度的标志物。我们的结果表明，TBM病例中脂肪酸和能量代谢的紊乱很重要，因为游离肉碱通过将长链脂肪酸转运到线粒体中进行能量产生，在脂肪酸的β氧化中起着关键作用。
