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

脑脊液定量蛋白质组学分析显示 CD163、A2M 和全长 APP 是儿童细菌性脑膜炎的潜在诊断生物标志物

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作者:Ting Luo #, Sai Yang #, Yan Chen, Shulei Liu, Liming Yang, Nanfei Hu, Ye Ma, Jun Qiu, Kewei Wang, Liping Li, Lihong Tan

Background

Bacterial meningitis (BM) is a life-threatening infectious disease of the central nervous system in infants and children. To date, no diagnostic

Conclusions

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

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.

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