Mass spectrometry-based proteomic techniques to identify cerebrospinal fluid biomarkers for diagnosing suspected central nervous system infections. A systematic review

Abstract

Objectives: Central nervous system (CNS) infections account for considerable death and disability every year. An urgent research priority is scaling up diagnostic capacity, and introduction of point-of-care tests. We set out to assess current evidence for the application of mass spectrometry (MS) peptide sequencing in identification of diagnostic biomarkers for CNS infections. Methods: We performed a systematic review (PROSPERO-CRD42018104257) using PRISMA guidelines on use of MS to identify cerebrospinal fluid (CSF) biomarkers for diagnosing CNS infections. We searched PubMed, Embase, Web of Science, and Cochrane for articles published from 1 January 20 0 0 to 1 February 2019, and contacted experts. Inclusion criteria involved primary research except case reports, on the diagnosis of infectious diseases except HIV, applying MS to human CSF samples, and English language. Results: 4,620 papers were identified, of which 11 were included, largely confined to pre-clinical biomarker discovery, and eight (73%) published in the last five years. 6 studies performed further work termed verification or validation. In 2 of these studies, it was possible to extract data on sensitivity and specificity of the biomarkers detected by ELISA, ranging from 89-94% and 58-92% respectively. Conclusions: The findings demonstrate feasibility and potential of the methods in a variety of infectious diseases, but emphasise the need for strong interdisciplinary collaborations to ensure appropriate study design and biomarker validation.

Diagnostic Cerebrospinal Fluid Biomarker Discovery and Validation in Patients with Central Nervous System Infections

“…CSF cathelicidin for BM (22)) detected by original mass-spectrometry analysis). Likewise, we did not assess the diagnostic performance of LCN2 against and/or in combination newly proposed biomarkers for CNS infections such as procalcitonin and heparin-binding protein for BM (7, 9, 23–25), and CSF lipoarabinomannan for TBM (26). Additionally, we only focused our analysis on adults, leaving the utility potential of LCN2 in pediatric CNS infections unknown.…”

“…In spite of these limitations, the strengths of our study include that it represents the largest and most comprehensive mass-spectrometry-based biomarker discovery investigation focusing on patients with various clinical entities of CNS infections to date (7). The study was also conducted in Vietnam and therefore includes all the major infectious causes of CNS infections seen globally.…”

“…Over the last decade, mass-spectrometry has emerged as a sensitive, hypothesis-free approach for the discovery of novel diagnostic biomarkers in both communicable (e.g. CNS infections) and non-communicable diseases (7–9). However, previous biomarker-discovery studies of CNS infections have either been limited in sample size or have not included a validation phase (7).…”

“…CNS infections) and non-communicable diseases (7–9). However, previous biomarker-discovery studies of CNS infections have either been limited in sample size or have not included a validation phase (7). Here, using a mass-spectrometry based approach we first searched for novel diagnostic biomarkers in cerebrospinal fluid (CSF) samples from a discovery cohort of 45 patients with brain infections.…”

Recent advances in the bioanalytical methods of polyethylene glycols and PEGylated pharmaceuticals

“…(IV) The schematic of enhancement effect of a variable topology of a membrane‐tethered anti‐poly(ethylene glycol) antibody on the sensitivity for quantifying PEG and PEGylated molecules. Reprinted with permission from [135] Copyright © (2017) American Chemical Society…”