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. 2022 May 6;20(1):8.
doi: 10.1186/s12953-022-00191-5.

Quantitative proteomic analysis of cerebrospinal fluid reveals CD163, A2M and full-length APP as potential diagnostic biomarkers of paediatric bacterial meningitis

Ting Luo #  1 , Sai Yang #  2 , Yan Chen  1 , Shulei Liu  2 , Liming Yang  2 , Nanfei Hu  2 , Ye Ma  2 , Jun Qiu  1 , Kewei Wang  1 , Liping Li  3 , Lihong Tan  4
Affiliations

Quantitative proteomic analysis of cerebrospinal fluid reveals CD163, A2M and full-length APP as potential diagnostic biomarkers of paediatric bacterial meningitis

Ting Luo et al. Proteome Sci. .

Abstract

Background: Bacterial meningitis (BM) is a life-threatening infectious disease of the central nervous system in infants and children. To date, no diagnostic methods for the early and precise diagnosis of paediatric BM have been developed.

Methods: A label-free cerebrospinal fluid (CSF) quantitative proteomic analysis of 8 patients with confirmed or suspected BM, 9 patients with confirmed or suspected viral meningitis (VM) and 6 non-CNS-infected hospital patients was performed via high-resolution LC-MS/MS.

Results: Our CSF proteomic analysis allowed the identification of critical differences between the BM and non-BM groups. Compared to the proteomes of the non-BM groups, the proteome of the paediatric BM group was characterized by upregulation of complement and coagulation cascades, regulation of IGF transport, uptake by IGF-binding proteins and acute inflammatory response, downregulation of developmental growth, and metabolism of carbohydrates. Moreover, the levels of CD163, A2M and full-length APP in CSF showed excellent diagnostic performance for paediatric BM, with AUC values of 0.911 (95% CI: 0.839-0.984), 0.908 (95% CI: 0.816-1.000) and 0.944 (95% CI: 0.86, 1.000), respectively. Among them, A2M and full-length APP are reported here for the first time as potential diagnostic biomarkers of BM. The findings imply that peptidase regulator activity plays an important role in BM and provide potential novel targets for precision medicine in paediatric BM.

Conclusions: CD163, A2M and full-length APP are validated as potential diagnostic biomarkers of paediatric BM.

Keywords: Cerebrospinal fluid; Diagnostic biomarkers; Infection of the central nervous system; Paediatric bacterial meningitis; Proteomics.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Workflow of the study design
Fig. 2
Fig. 2
Comparison of CSF proteome profiles between the BM and non-BM groups. A Two-dimensional scatter plot of principal component analysis (PCA) distribution of all samples using quantified proteins; B Histogram of the number distribution of DEPs in different comparison groups
Fig. 3
Fig. 3
Heatmap of the DEPs between the BM and non-BM groups and bar graph of the top enriched biological functions of these DEPs in both comparison groups
Fig. 4
Fig. 4
Visualization of the network of major enriched functions and their associated genes
Fig. 5
Fig. 5
Validation of the protein expression levels of CD163, A2M, sAPPα and full-length APP in CSF and evaluation of their diagnostic performance in paediatric BM
See this image and copyright information in PMC

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