Human Lyme Neuroborreliosis LC-MS (plasma)

Lyme neuroborreliosis (LNB) is a nervous system infection caused by tick-borne spirochetes of the Borrelia burgdorferi sensu lato complex and is one of the most frequent bacterial infections of the nervous system in Europe. Early diagnosis remains challenging due to limited sensitivity and specificity of current tests and the need for invasive lumbar punctures, highlighting the need for improved and potentially less invasive diagnostic tools. In this study, we used bottom-up proteomics to analyze 308 cerebrospinal fluid (CSF) samples and 207 plasma samples from well-characterized cohorts, including patients with LNB, viral meningitis, other manifestations of Lyme borreliosis without central nervous system involvement, and controls with normal CSF findings. We identified diagnostic panels of regulated proteins and evaluated their performance using machine learning–based classifiers. The resulting models distinguished LNB from viral meningitis and controls in CSF with areas under the ROC curve (AUC) of 0.92 and 0.90, respectively. In plasma, LNB was distinguished from controls with an AUC of 0.80. These findings suggest a potential diagnostic role for proteomics-based biomarker panels in LNB and provide a large-scale, publicly available proteomic resource for further biomarker discovery and validation studies. NOTE the CSF search and raw files can be found in PXD067474.