Lipocalin 2 Proposed as Biomarker for Bacterial Meningitis

Central nervous system (CNS) infections cause significant mortality and morbidity worldwide. Common CNS infections include bacterial meningitis (BM) other than tuberculosis, viral encephalitis, tuberculous meningitis (TBM) and cryptococcal meningitis, but there are more than 100 documented infectious causes of CNS infections.

Clinical features are often insufficient to discriminate the likely cause and standard laboratory investigations identify the causative agent in less than 60% of cases. Critically, the clinical management of CNS infections varies according to its etiology. Therefore, rapid and accurate identification of the likely cause of the infection is essential to initiate appropriate therapy and improve patient outcome.

Scientists from the Oxford University Clinical Research Unit (Ho Chi Minh City, Vietnam) and their associates applied liquid chromatography tandem mass-spectrometry on 45 cerebrospinal fluid (CSF) samples from a cohort of adults with/without CNS infections to discover potential diagnostic biomarkers. They then validated the diagnostic performance of a selected biomarker candidate in an independent cohort of 364 consecutively treated adults with CNS infections admitted to a referral hospital in Vietnam.

Measurement of lipocalin 2 (LCN2) concentrations was performed on CSF samples and a subset of plasma samples of the study participants using monoclonal antibody based Quantikine ELISA kits (R&D Systems, Minneapolis, MN, USA) which costs around USD 10/test. CSF was analyzed as individual samples using proteomic platforms. MS/MS spectra were searched against the UniProt Homo Sapiens Reference proteome. Deamidation on asparagine and glutamine and oxidation on methionine were included as variable modifications.

The team identified LCN2 as a potential biomarker of BM other than tuberculous meningitis. The analysis of the validation cohort showed that LCN2 could discriminate BM from other CNS infections (including tuberculous meningitis, cryptococcal meningitis and viral/antibody-mediated encephalitis), with the sensitivity of 0.88, the specificity equaled 0.91 and the diagnostic odds ratio was 73.8. LCN2 outperformed other CSF markers (leukocytes, glucose, protein and lactate) commonly used in routine care worldwide. The combination of LCN2, CSF leukocytes, glucose, protein and lactate resulted in the highest diagnostic performance for BM (area under receiver-operating-characteristic-curve = 0.96).

The authors concluded that their results suggest that LCN2 is a sensitive and specific biomarker for discriminating BM from a broad spectrum of other CNS infections. A prospective study is needed to assess the diagnostic utility of LCN2 in the diagnosis and management of CNS infections. The study was published on July 10, 2020 in the journal Clinical Microbiology and Infection.

Related Links:
Oxford University Clinical Research Unit
R&D Systems