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Updated: Dec 31, 2025
A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
Published on: October 20, 2016
Phosphatidylcholine PC ae C44:6 in cerebrospinal fluid is a sensitive biomarker for bacterial meningitis
Leonardo Silva de Araujo1,2,3, Kevin Pessler1, Kurt-Wolfram Sühs4,5
1Research Group "Biomarkers for Infectious Diseases", TWINCORE Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Str. 7, 30625, Hannover, Germany.
Background:
The timely diagnosis of bacterial meningitis is of utmost importance due to the need to institute antibiotic treatment as early as possible. Moreover, the differentiation from other causes of meningitis/encephalitis is critical because of differences in management such as the need for antiviral or immunosuppressive treatments. Considering our previously reported association between free membrane phospholipids in cerebrospinal fluid (CSF) and CNS involvement in neuroinfections we evaluated phosphatidylcholine PC ae C44:6, an integral constituent of cell membranes, as diagnostic biomarker for bacterial meningitis.
Methods:
We used tandem mass spectrometry to measure concentrations of PC ae C44:6 in cell-free CSF samples (n = 221) from patients with acute bacterial meningitis, neuroborreliosis, viral meningitis/encephalitis (herpes simplex virus, varicella zoster virus, enteroviruses), autoimmune neuroinflammation (anti-NMDA-receptor autoimmune encephalitis, multiple sclerosis), facial nerve and segmental herpes zoster (shingles), and noninflammatory CNS disorders (Bell's palsy, Tourette syndrome, normal pressure hydrocephalus).
Results:
PC ae C44:6 concentrations were significantly higher in bacterial meningitis than in all other diagnostic groups, and were higher in patients with a classic bacterial meningitis pathogen (e.g. Streptococcus pneumoniae, Neisseria meningitidis, Staphylococcus aureus) than in those with less virulent or opportunistic pathogens as causative agents (P = 0.026). PC ae C44:6 concentrations were only moderately associated with CSF cell count (Spearman's ρ = 0.45; P = 0.009), indicating that they do not merely reflect neuroinflammation. In receiver operating characteristic curve analysis, PC ae C44:6 equaled CSF cell count in the ability to distinguish bacterial meningitis from viral meningitis/encephalitis and autoimmune CNS disorders (AUC 0.93 both), but had higher sensitivity (91% vs. 41%) and negative predictive value (98% vs. 89%). A diagnostic algorithm comprising cell count, lactate and PC ae C44:6 had a sensitivity of 97% (specificity 87%) and negative predictive value of 99% (positive predictive value 61%) and correctly diagnosed three of four bacterial meningitis samples that were misclassified by cell count and lactate due to low values not suggestive of bacterial meningitis.
Conclusions:
Increased CSF PC ae C44:6 concentrations in bacterial meningitis likely reflect ongoing CNS cell membrane stress or damage and have potential as additional, sensitive biomarker to diagnose bacterial meningitis in patients with less pronounced neuroinflammation.
Insights
Phosphatidylcholine PC ae C44:6 is a promising biomarker for bacterial meningitis diagnosis. Elevated levels in cerebrospinal fluid (CSF) help differentiate bacterial meningitis from other neurological conditions, improving early treatment initiation.
Area of Science:
- Neuroscience
- Biochemistry
- Clinical Diagnostics
Background:
- Timely diagnosis of bacterial meningitis is crucial for effective antibiotic treatment.
- Differentiating bacterial meningitis from other CNS infections (viral, autoimmune) is critical for appropriate management.
- Previous research linked free membrane phospholipids in CSF to CNS infections.
Purpose of the Study:
- To evaluate phosphatidylcholine PC ae C44:6 as a diagnostic biomarker for bacterial meningitis.
- To assess the utility of PC ae C44:6 in distinguishing bacterial meningitis from other neurological disorders.
Main Methods:
- Tandem mass spectrometry was used to measure PC ae C44:6 concentrations in cerebrospinal fluid (CSF) from 221 patients.
- Patient groups included bacterial meningitis, neuroborreliosis, viral meningitis/encephalitis, autoimmune neuroinflammation, and noninflammatory CNS disorders.
- Receiver operating characteristic (ROC) curve analysis was employed to evaluate diagnostic performance.
Main Results:
- PC ae C44:6 concentrations were significantly higher in bacterial meningitis compared to all other groups.
- PC ae C44:6 demonstrated high diagnostic accuracy (AUC 0.93) comparable to CSF cell count in distinguishing bacterial from viral/autoimmune meningitis.
- PC ae C44:6 showed higher sensitivity (91%) and negative predictive value (98%) than CSF cell count (41%, 89%).
- A diagnostic algorithm including PC ae C44:6 improved bacterial meningitis detection, correctly classifying cases missed by cell count and lactate.
Conclusions:
- Elevated CSF PC ae C44:6 concentrations suggest CNS cell membrane stress or damage in bacterial meningitis.
- PC ae C44:6 shows potential as a sensitive biomarker for diagnosing bacterial meningitis, especially in cases with subtle neuroinflammation.
- This biomarker can aid in differentiating bacterial meningitis from other neurological conditions, facilitating timely and appropriate patient management.
