Dataset Information

Monitoring of Protein Biomarkers of Inflammation in Human Traumatic Brain Injury Using Microdialysis and Proximity Extension Assay Technology in Neurointensive Care.

ABSTRACT: Traumatic brain injury (TBI) is followed by secondary injury mechanisms strongly involving neuroinflammation. To monitor the complex inflammatory cascade in human TBI, we used cerebral microdialysis (MD) and multiplex proximity extension assay (PEA) technology and simultaneously measured levels of 92 protein biomarkers of inflammation in MD samples every three hours for five days in 10 patients with severe TBI under neurointensive care. One ?L MD samples were incubated with paired oligonucleotide-conjugated antibodies binding to each protein, allowing quantification by real-time quantitative polymerase chain reaction. Sixty-nine proteins were suitable for statistical analysis. We found five different patterns with either early (<48?h; e.g., CCL20, IL6, LIF, CCL3), mid (48-96?h; e.g., CCL19, CXCL5, CXCL10, MMP1), late (>96?h; e.g., CD40, MCP2, MCP3), biphasic peaks (e.g., CXCL1, CXCL5, IL8) or stable (e.g., CCL4, DNER, VEGFA)/low trends. High protein levels were observed for e.g., CXCL1, CXCL10, MCP1, MCP2, IL8, while e.g., CCL28 and MCP4 were detected at low levels. Several proteins (CCL8, -19, -20, -23, CXCL1, -5, -6, -9, -11, CST5, DNER, Flt3L, and SIRT2) have not been studied previously in human TBI. Cross-correlation analysis revealed that LIF and CXCL5 may play a central role in the inflammatory cascade. This study provides a unique data set with individual temporal trends for potential inflammatory biomarkers in patients with TBI. We conclude that the combination of MD and PEA is a powerful tool to map the complex inflammatory cascade in the injured human brain. The technique offers new possibilities of protein profiling of complex secondary injury pathways.

SUBMITTER: Dyhrfort P

PROVIDER: S-EPMC6761596 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Monitoring of Protein Biomarkers of Inflammation in Human Traumatic Brain Injury Using Microdialysis and Proximity Extension Assay Technology in Neurointensive Care.

Dyhrfort Philip P Shen Qiujin Q Clausen Fredrik F Thulin Måns M Enblad Per P Kamali-Moghaddam Masood M Lewén Anders A Hillered Lars L

Journal of neurotrauma 20190617 20

Traumatic brain injury (TBI) is followed by secondary injury mechanisms strongly involving neuroinflammation. To monitor the complex inflammatory cascade in human TBI, we used cerebral microdialysis (MD) and multiplex proximity extension assay (PEA) technology and simultaneously measured levels of 92 protein biomarkers of inflammation in MD samples every three hours for five days in 10 patients with severe TBI under neurointensive care. One μL MD samples were incubated with paired oligonucleotid ...[more]

PMID: 31017044

Similar Datasets

Project description:Cerebral protein profiling in traumatic brain injury (TBI) is needed to better comprehend secondary injury pathways. Cerebral microdialysis (CMD), in combination with the proximity extension assay (PEA) technique, has great potential in this field. By using PEA, we have previously screened >500 proteins from CMD samples collected from TBI patients. In this study, we customized a PEA panel prototype of 21 selected candidate protein biomarkers, involved in inflammation (13), neuroplasticity/-repair (six), and axonal injury (two). The aim was to study their temporal dynamics and relation to age, structural injury, and clinical outcome. Ten patients with severe TBI and CMD monitoring, who were treated in the Neurointensive Care Unit, Uppsala University Hospital, Sweden, were included. Hourly CMD samples were collected for up to 7 days after trauma and analyzed with the 21-plex PEA panel. Seventeen of the 21 proteins from the CMD sample analyses showed significantly different mean levels between days. Early peaks (within 48 h) were noted with interleukin (IL)-1β, IL-6, IL-8, granulocyte colony-stimulating factor, transforming growth factor alpha, brevican, junctional adhesion molecule B, and neurocan. C-X-C motif chemokine ligand 10 peaked after 3 days. Late peaks (>5 days) were noted with interleukin-1 receptor antagonist (IL-1ra), monocyte chemoattractant protein (MCP)-2, MCP-3, urokinase-type plasminogen activator, Dickkopf-related protein 1, and DRAXIN. IL-8, neurofilament heavy chain, and TAU were biphasic. Age (above/below 22 years) interacted with the temporal dynamics of IL-6, IL-1ra, vascular endothelial growth factor, MCP-3, and TAU. There was no association between radiological injury (Marshall grade) or clinical outcome (Extended Glasgow Outcome Scale) with the protein expression pattern. The PEA method is a highly sensitive molecular tool for protein profiling from cerebral tissue in TBI. The novel TBI dedicated 21-plex panel showed marked regulation of proteins belonging to the inflammation, plasticity/repair, and axonal injury families. The method may enable important insights into complex injury processes on a molecular level that may be of value in future efforts to tailor pharmacological TBI trials to better address specific disease processes and optimize timing of treatments.

Project description:BackgroundAlthough the potential of biomarkers to aid in early detection of colorectal cancer (CRC) is recognized and numerous biomarker candidates have been reported in the literature, to date only few molecular markers have been approved for daily clinical use.MethodsIn order to improve the translation of biomarkers from the bench to clinical practice we initiated a biomarker study focusing on a novel technique, the proximity extension assay, with multiplexing capability and the possible additive effect obtained from biomarker panels. We performed a screening of 74 different biomarkers in plasma derived from a case-control sample set consisting of symptomatic individuals representing CRC patients, patients with adenoma, patients with non-neoplastic large bowel diseases and healthy individuals.ResultsAfter statistical evaluation we found 12 significant indicators of CRC and the receiver operating characteristic (ROC) curve of Carcinoembryonic antigen (CEA), Transferrin Receptor-1 (TFRC), Macrophage migration inhibitory factor (MIF), Osteopontin (OPN/SPP1) and cancer antigen 242 (CA242) showed additive effect. This biomarker panel identified CRC patients with a sensitivity of 56% at 90% specificity and thus the performance is sufficiently high to further investigate this combination of five proteins as serological biomarkers for detection of CRC. Furthermore, when applying the indicators to identify early-stage CRC a combination of CEA, TFRC and CA242 resulted in a ROC curve with an area under the curve of 0.861.ConclusionsFive plasma protein biomarkers were found to be potential CRC discriminators and three of these were additionally found to be discriminators of early-stage CRC. These explorative data in symptomatic individuals demonstrates the feasibility of the multiplex proximity extension assay for screening of potential serological protein biomarkers and warrants independent analyses in a larger sample cohort, including asymptomatic individuals, to further validate the performances of our CRC biomarker panel.

Dataset Information

Monitoring of Protein Biomarkers of Inflammation in Human Traumatic Brain Injury Using Microdialysis and Proximity Extension Assay Technology in Neurointensive Care.

Publications

Monitoring of Protein Biomarkers of Inflammation in Human Traumatic Brain Injury Using Microdialysis and Proximity Extension Assay Technology in Neurointensive Care.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets