Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) proteomic profiling of cerebrospinal fluid in the diagnosis of enteroviral meningitis: a proof-of-principle study

Abstract

The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for diagnosing viral infections by directly testing clinical specimens has not previously been explored. In this proof-of-principle study, we tested the hypothesis that proteomic profiling of cerebrospinal fluid (CSF) by mass spectrometry may be useful in the diagnosis of enteroviral (EV) meningitis. A total of 114 cryopreserved CSF samples were analyzed, of which 47 were positive for EV and 67 were negative. Total CSF proteins were precipitated and subjected to MALDI-TOF-MS analysis in a low (2–20 kDa) molecular weight range using a MicroFlex LT mass spectrometer. The whole data set was randomly split into a training set (n = 76 specimens) and a validation set (n = 38 samples). Backward/forward stepwise logistic regression analyses identified 30 peaks that were differentially present in EV-positive and EV-negative specimens. These were used to build a model which displayed an overall classification accuracy of 93%. The discriminative ability of the model was confirmed by using a validation sample set (overall accuracy 83%). In fact, the model was able to correctly classify 61 out of 67 EV-negative samples and 42 out of 47 EV-positive specimens. EV meningitis is associated with a distinctive protein profile that may be directly detectable in CSF specimens by MALDI-TOF-MS.