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Exploring serum glycome patterns after moderate to severe traumatic brain injury: A prospective pilot study
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 moderat...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218141/ https://www.ncbi.nlm.nih.gov/pubmed/35755600 http://dx.doi.org/10.1016/j.eclinm.2022.101494 |
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author | Mondello, Stefania Sandner, Viktor Goli, Mona Czeiter, Endre Amrein, Krisztina Kochanek, Patrick M. Gautam, Sakshi Cho, Byeong Gwan Morgan, Ryan Nehme, Ali Fiumara, Giacomo Eid, Ali H. Barsa, Chloe Haidar, Muhammad Ali Buki, Andras Kobeissy, Firas H. Mechref, Yehia |
author_facet | Mondello, Stefania Sandner, Viktor Goli, Mona Czeiter, Endre Amrein, Krisztina Kochanek, Patrick M. Gautam, Sakshi Cho, Byeong Gwan Morgan, Ryan Nehme, Ali Fiumara, Giacomo Eid, Ali H. Barsa, Chloe Haidar, Muhammad Ali Buki, Andras Kobeissy, Firas H. Mechref, Yehia |
author_sort | Mondello, Stefania |
collection | PubMed |
description | 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). |
format | Online Article Text |
id | pubmed-9218141 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-92181412022-06-24 Exploring serum glycome patterns after moderate to severe traumatic brain injury: A prospective pilot study Mondello, Stefania Sandner, Viktor Goli, Mona Czeiter, Endre Amrein, Krisztina Kochanek, Patrick M. Gautam, Sakshi Cho, Byeong Gwan Morgan, Ryan Nehme, Ali Fiumara, Giacomo Eid, Ali H. Barsa, Chloe Haidar, Muhammad Ali Buki, Andras Kobeissy, Firas H. Mechref, Yehia eClinicalMedicine Articles 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). Elsevier 2022-06-17 /pmc/articles/PMC9218141/ /pubmed/35755600 http://dx.doi.org/10.1016/j.eclinm.2022.101494 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Articles Mondello, Stefania Sandner, Viktor Goli, Mona Czeiter, Endre Amrein, Krisztina Kochanek, Patrick M. Gautam, Sakshi Cho, Byeong Gwan Morgan, Ryan Nehme, Ali Fiumara, Giacomo Eid, Ali H. Barsa, Chloe Haidar, Muhammad Ali Buki, Andras Kobeissy, Firas H. Mechref, Yehia Exploring serum glycome patterns after moderate to severe traumatic brain injury: A prospective pilot study |
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 | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218141/ https://www.ncbi.nlm.nih.gov/pubmed/35755600 http://dx.doi.org/10.1016/j.eclinm.2022.101494 |
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