Quantitative proteomic analysis of cerebrospinal fluid reveals CD163, A2M and full-length APP as potential diagnostic biomarkers of paediatric bacterial meningitis
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) quanti...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-05-01
|
| Series: | Proteome Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12953-022-00191-5 |
| _version_ | 1818191504825384960 |
|---|---|
| author | Ting Luo Sai Yang Yan Chen Shulei Liu Liming Yang Nanfei Hu Ye Ma Jun Qiu Kewei Wang Liping Li Lihong Tan |
| author_facet | Ting Luo Sai Yang Yan Chen Shulei Liu Liming Yang Nanfei Hu Ye Ma Jun Qiu Kewei Wang Liping Li Lihong Tan |
| author_sort | Ting Luo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T00:15:40Z |
| format | Article |
| id | doaj.art-3eb516771f884a9290c7446b687b36f9 |
| institution | Directory Open Access Journal |
| issn | 1477-5956 |
| language | English |
| last_indexed | 2024-12-12T00:15:40Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Proteome Science |
| spelling | doaj.art-3eb516771f884a9290c7446b687b36f92022-12-22T00:44:51ZengBMCProteome Science1477-59562022-05-0120111110.1186/s12953-022-00191-5Quantitative proteomic analysis of cerebrospinal fluid reveals CD163, A2M and full-length APP as potential diagnostic biomarkers of paediatric bacterial meningitisTing Luo0Sai Yang1Yan Chen2Shulei Liu3Liming Yang4Nanfei Hu5Ye Ma6Jun Qiu7Kewei Wang8Liping Li9Lihong Tan10Pediatrics Research Institute of Hunan Province, Hunan Children’s HospitalDepartment of Neurology, Hunan Children’s HospitalPediatrics Research Institute of Hunan Province, Hunan Children’s HospitalDepartment of Neurology, Hunan Children’s HospitalDepartment of Neurology, Hunan Children’s HospitalDepartment of Neurology, Hunan Children’s HospitalDepartment of Neurology, Hunan Children’s HospitalPediatrics Research Institute of Hunan Province, Hunan Children’s HospitalPediatrics Research Institute of Hunan Province, Hunan Children’s HospitalPediatrics Research Institute of Hunan Province, Hunan Children’s HospitalPediatrics Research Institute of Hunan Province, Hunan Children’s HospitalAbstract 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.https://doi.org/10.1186/s12953-022-00191-5Paediatric bacterial meningitisCerebrospinal fluidDiagnostic biomarkersProteomicsInfection of the central nervous system |
| spellingShingle | Ting Luo Sai Yang Yan Chen Shulei Liu Liming Yang Nanfei Hu Ye Ma Jun Qiu Kewei Wang Liping Li Lihong Tan Quantitative proteomic analysis of cerebrospinal fluid reveals CD163, A2M and full-length APP as potential diagnostic biomarkers of paediatric bacterial meningitis Proteome Science Paediatric bacterial meningitis Cerebrospinal fluid Diagnostic biomarkers Proteomics Infection of the central nervous system |
| title | Quantitative proteomic analysis of cerebrospinal fluid reveals CD163, A2M and full-length APP as potential diagnostic biomarkers of paediatric bacterial meningitis |
| title_full | Quantitative proteomic analysis of cerebrospinal fluid reveals CD163, A2M and full-length APP as potential diagnostic biomarkers of paediatric bacterial meningitis |
| title_fullStr | Quantitative proteomic analysis of cerebrospinal fluid reveals CD163, A2M and full-length APP as potential diagnostic biomarkers of paediatric bacterial meningitis |
| title_full_unstemmed | Quantitative proteomic analysis of cerebrospinal fluid reveals CD163, A2M and full-length APP as potential diagnostic biomarkers of paediatric bacterial meningitis |
| title_short | Quantitative proteomic analysis of cerebrospinal fluid reveals CD163, A2M and full-length APP as potential diagnostic biomarkers of paediatric bacterial meningitis |
| title_sort | quantitative proteomic analysis of cerebrospinal fluid reveals cd163 a2m and full length app as potential diagnostic biomarkers of paediatric bacterial meningitis |
| topic | Paediatric bacterial meningitis Cerebrospinal fluid Diagnostic biomarkers Proteomics Infection of the central nervous system |
| url | https://doi.org/10.1186/s12953-022-00191-5 |
| work_keys_str_mv | AT tingluo quantitativeproteomicanalysisofcerebrospinalfluidrevealscd163a2mandfulllengthappaspotentialdiagnosticbiomarkersofpaediatricbacterialmeningitis AT saiyang quantitativeproteomicanalysisofcerebrospinalfluidrevealscd163a2mandfulllengthappaspotentialdiagnosticbiomarkersofpaediatricbacterialmeningitis AT yanchen quantitativeproteomicanalysisofcerebrospinalfluidrevealscd163a2mandfulllengthappaspotentialdiagnosticbiomarkersofpaediatricbacterialmeningitis AT shuleiliu quantitativeproteomicanalysisofcerebrospinalfluidrevealscd163a2mandfulllengthappaspotentialdiagnosticbiomarkersofpaediatricbacterialmeningitis AT limingyang quantitativeproteomicanalysisofcerebrospinalfluidrevealscd163a2mandfulllengthappaspotentialdiagnosticbiomarkersofpaediatricbacterialmeningitis AT nanfeihu quantitativeproteomicanalysisofcerebrospinalfluidrevealscd163a2mandfulllengthappaspotentialdiagnosticbiomarkersofpaediatricbacterialmeningitis AT yema quantitativeproteomicanalysisofcerebrospinalfluidrevealscd163a2mandfulllengthappaspotentialdiagnosticbiomarkersofpaediatricbacterialmeningitis AT junqiu quantitativeproteomicanalysisofcerebrospinalfluidrevealscd163a2mandfulllengthappaspotentialdiagnosticbiomarkersofpaediatricbacterialmeningitis AT keweiwang quantitativeproteomicanalysisofcerebrospinalfluidrevealscd163a2mandfulllengthappaspotentialdiagnosticbiomarkersofpaediatricbacterialmeningitis AT lipingli quantitativeproteomicanalysisofcerebrospinalfluidrevealscd163a2mandfulllengthappaspotentialdiagnosticbiomarkersofpaediatricbacterialmeningitis AT lihongtan quantitativeproteomicanalysisofcerebrospinalfluidrevealscd163a2mandfulllengthappaspotentialdiagnosticbiomarkersofpaediatricbacterialmeningitis |