Exploring serum glycome patterns after moderate to severe traumatic brain injury: A prospective pilot study
Summary: Background: Glycans play essential functional roles in the nervous system and their pathobiological relevance has become increasingly recognized in numerous brain disorders, but not fully explored in traumatic brain injury (TBI). We investigated longitudinal glycome patterns in patients wi...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | EClinicalMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537022002243 |
| _version_ | 1828725595583807488 |
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| author | Stefania Mondello Viktor Sandner Mona Goli Endre Czeiter Krisztina Amrein Patrick M. Kochanek Sakshi Gautam Byeong Gwan Cho Ryan Morgan Ali Nehme Giacomo Fiumara Ali H. Eid Chloe Barsa Muhammad Ali Haidar Andras Buki Firas H. Kobeissy Yehia Mechref |
| author_facet | Stefania Mondello Viktor Sandner Mona Goli Endre Czeiter Krisztina Amrein Patrick M. Kochanek Sakshi Gautam Byeong Gwan Cho Ryan Morgan Ali Nehme Giacomo Fiumara Ali H. Eid Chloe Barsa Muhammad Ali Haidar Andras Buki Firas H. Kobeissy Yehia Mechref |
| author_sort | Stefania Mondello |
| collection | DOAJ |
| description | Summary: Background: Glycans play essential functional roles in the nervous system and their pathobiological relevance has become increasingly recognized in numerous brain disorders, but not fully explored in traumatic brain injury (TBI). We investigated longitudinal glycome patterns in patients with moderate to severe TBI (Glasgow Coma Scale [GCS] score ≤12) to characterize glyco-biomarker signatures and their relation to clinical features and long-term outcome. Methods: This prospective single-center observational study included 51 adult patients with TBI (GCS ≤12) admitted to the neurosurgical unit of the University Hospital of Pecs, Pecs, Hungary, between June 2018 and April 2019. We used a high-throughput liquid chromatography–tandem mass spectrometry platform to assess serum levels of N-glycans up to 3 days after injury. Outcome was assessed using the Glasgow Outcome Scale-Extended (GOS-E) at 12 months post-injury. Multivariate statistical techniques, including principal component analysis and orthogonal partial least squares discriminant analysis, were used to analyze glycomics data and define highly influential structures driving class distinction. Receiver operating characteristic analyses were used to determine prognostic accuracy. Findings: We identified 94 N-glycans encompassing all typical structural types, including oligomannose, hybrid, and complex-type entities. Levels of high mannose, hybrid and sialylated structures were temporally altered (p<0·05). Four influential glycans were identified. Two brain-specific structures, HexNAc5Hex3DeoxyHex0NeuAc0 and HexNAc5Hex4DeoxyHex0NeuAc1, were substantially increased early after injury in patients with unfavorable outcome (GOS-E≤4) (area under the curve [AUC]=0·75 [95%CI 0·59-0·90] and AUC=0·71 [0·52-0·89], respectively). Serum levels of HexNAc7Hex7DeoxyHex1NeuAc2 and HexNAc8Hex6DeoxyHex0NeuAc0 were persistently increased in patients with favorable outcome, but undetectable in those with unfavorable outcome. Levels of HexNAc5Hex4DeoxyHex0NeuAc1 were acutely elevated in patients with mass lesions and in those requiring decompressive craniectomy. Interpretation: In spite of the exploratory nature of the study and the relatively small number of patients, our results provide to the best of our knowledge initial evidence supporting the utility of glycomics approaches for biomarker discovery and patient phenotyping in TBI. Further larger multicenter studies will be required to validate our findings and to determine their pathobiological value and potential applications in practice. Funding: This work was funded by the Italian Ministry of Health (grant number GR-2013-02354960), and also partially supported by a NIH grant (1R01GM112490-08). |
| first_indexed | 2024-04-12T13:29:42Z |
| format | Article |
| id | doaj.art-0728102a99474dfbbc49395e624e36e7 |
| institution | Directory Open Access Journal |
| issn | 2589-5370 |
| language | English |
| last_indexed | 2024-04-12T13:29:42Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj.art-0728102a99474dfbbc49395e624e36e72022-12-22T03:31:12ZengElsevierEClinicalMedicine2589-53702022-08-0150101494Exploring serum glycome patterns after moderate to severe traumatic brain injury: A prospective pilot studyStefania Mondello0Viktor Sandner1Mona Goli2Endre Czeiter3Krisztina Amrein4Patrick M. Kochanek5Sakshi Gautam6Byeong Gwan Cho7Ryan Morgan8Ali Nehme9Giacomo Fiumara10Ali H. Eid11Chloe Barsa12Muhammad Ali Haidar13Andras Buki14Firas H. Kobeissy15Yehia Mechref16Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy; Corresponding author.Sartorius Data Analytics, Sartorius Stedim Austria GmbH, 1030 Vienna, AustriaDepartment of Chemistry and Biochemistry, Texas Tech University, Box 41061, Lubbock, TX 79409-1061, USADepartment of Neurosurgery, University of Pécs, H-7623 Pécs, Hungary; Neurotrauma Research Group, Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary; MTA-PTE Clinical Neuroscience MR Research Group, H-7623 Pécs, HungaryDepartment of Neurosurgery, University of Pécs, H-7623 Pécs, Hungary; Neurotrauma Research Group, Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary; MTA-PTE Clinical Neuroscience MR Research Group, H-7623 Pécs, HungaryDepartments of Critical Care Medicine, Pediatrics, Anesthesiology, and Clinical and Translational Science, University of Pittsburgh School of Medicine, and UPMC Children's Hospital of Pittsburgh, Pittsburgh 15224, USADepartment of Chemistry and Biochemistry, Texas Tech University, Box 41061, Lubbock, TX 79409-1061, USADepartment of Chemistry and Biochemistry, Texas Tech University, Box 41061, Lubbock, TX 79409-1061, USADepartment of Chemistry and Biochemistry, Texas Tech University, Box 41061, Lubbock, TX 79409-1061, USADepartment of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via Consolare Valeria 1, 98125 Messina, ItalyDepartment of Mathematical and Computer Science, Physical Sciences and Earth Sciences, University of Messina, 98100 Messina, ItalyDepartment of Biochemistry and Molecular Genetics, American University of Beirut, 1107-2020 Beirut, Lebanon; Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, QatarDepartment of Biochemistry and Molecular Genetics, American University of Beirut, 1107-2020 Beirut, LebanonDepartment of Biochemistry and Molecular Genetics, American University of Beirut, 1107-2020 Beirut, LebanonDepartment of Neurosurgery, University of Pécs, H-7623 Pécs, Hungary; Neurotrauma Research Group, Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary; MTA-PTE Clinical Neuroscience MR Research Group, H-7623 Pécs, HungaryDepartment of Biochemistry and Molecular Genetics, American University of Beirut, 1107-2020 Beirut, Lebanon; Department of Psychiatry and Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USADepartment of Chemistry and Biochemistry, Texas Tech University, Box 41061, Lubbock, TX 79409-1061, USA; Corresponding author.Summary: Background: Glycans play essential functional roles in the nervous system and their pathobiological relevance has become increasingly recognized in numerous brain disorders, but not fully explored in traumatic brain injury (TBI). We investigated longitudinal glycome patterns in patients with moderate to severe TBI (Glasgow Coma Scale [GCS] score ≤12) to characterize glyco-biomarker signatures and their relation to clinical features and long-term outcome. Methods: This prospective single-center observational study included 51 adult patients with TBI (GCS ≤12) admitted to the neurosurgical unit of the University Hospital of Pecs, Pecs, Hungary, between June 2018 and April 2019. We used a high-throughput liquid chromatography–tandem mass spectrometry platform to assess serum levels of N-glycans up to 3 days after injury. Outcome was assessed using the Glasgow Outcome Scale-Extended (GOS-E) at 12 months post-injury. Multivariate statistical techniques, including principal component analysis and orthogonal partial least squares discriminant analysis, were used to analyze glycomics data and define highly influential structures driving class distinction. Receiver operating characteristic analyses were used to determine prognostic accuracy. Findings: We identified 94 N-glycans encompassing all typical structural types, including oligomannose, hybrid, and complex-type entities. Levels of high mannose, hybrid and sialylated structures were temporally altered (p<0·05). Four influential glycans were identified. Two brain-specific structures, HexNAc5Hex3DeoxyHex0NeuAc0 and HexNAc5Hex4DeoxyHex0NeuAc1, were substantially increased early after injury in patients with unfavorable outcome (GOS-E≤4) (area under the curve [AUC]=0·75 [95%CI 0·59-0·90] and AUC=0·71 [0·52-0·89], respectively). Serum levels of HexNAc7Hex7DeoxyHex1NeuAc2 and HexNAc8Hex6DeoxyHex0NeuAc0 were persistently increased in patients with favorable outcome, but undetectable in those with unfavorable outcome. Levels of HexNAc5Hex4DeoxyHex0NeuAc1 were acutely elevated in patients with mass lesions and in those requiring decompressive craniectomy. Interpretation: In spite of the exploratory nature of the study and the relatively small number of patients, our results provide to the best of our knowledge initial evidence supporting the utility of glycomics approaches for biomarker discovery and patient phenotyping in TBI. Further larger multicenter studies will be required to validate our findings and to determine their pathobiological value and potential applications in practice. Funding: This work was funded by the Italian Ministry of Health (grant number GR-2013-02354960), and also partially supported by a NIH grant (1R01GM112490-08).http://www.sciencedirect.com/science/article/pii/S2589537022002243Traumatic brain injuryGlycosylationGlycomicsGlycomarkersBiomarkersSerum |
| spellingShingle | Stefania Mondello Viktor Sandner Mona Goli Endre Czeiter Krisztina Amrein Patrick M. Kochanek Sakshi Gautam Byeong Gwan Cho Ryan Morgan Ali Nehme Giacomo Fiumara Ali H. Eid Chloe Barsa Muhammad Ali Haidar Andras Buki Firas H. Kobeissy Yehia Mechref Exploring serum glycome patterns after moderate to severe traumatic brain injury: A prospective pilot study EClinicalMedicine Traumatic brain injury Glycosylation Glycomics Glycomarkers Biomarkers Serum |
| title | Exploring serum glycome patterns after moderate to severe traumatic brain injury: A prospective pilot study |
| title_full | Exploring serum glycome patterns after moderate to severe traumatic brain injury: A prospective pilot study |
| title_fullStr | Exploring serum glycome patterns after moderate to severe traumatic brain injury: A prospective pilot study |
| title_full_unstemmed | Exploring serum glycome patterns after moderate to severe traumatic brain injury: A prospective pilot study |
| title_short | Exploring serum glycome patterns after moderate to severe traumatic brain injury: A prospective pilot study |
| title_sort | exploring serum glycome patterns after moderate to severe traumatic brain injury a prospective pilot study |
| topic | Traumatic brain injury Glycosylation Glycomics Glycomarkers Biomarkers Serum |
| url | http://www.sciencedirect.com/science/article/pii/S2589537022002243 |
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