TY - JOUR
T1 - Unique diagnostic signatures of concussion in the saliva of male athletes
T2 - the study of concussion in Rugby Union through MicroRNAs (SCRUM)
AU - Di Pietro, Valentina
AU - O'Halloran, Patrick
AU - Watson, Callum N.
AU - Begum, Ghazala
AU - Acharjee, Animesh
AU - Yakoub, Kamal M.
AU - Bentley, Conor
AU - Davies, David J.
AU - Iliceto, Paolo
AU - Candilera, Gabriella
AU - Menon, David K.
AU - Cross, Matthew J.
AU - Stokes, Keith A.
AU - Kemp, Simon P.T.
AU - Belli, Antonio
N1 - Funding Information:
Funding The study was funded by the National Institute for Health Research (NIHR), Medical Research Council (MRC), Rugby Football Union, Midland Neuroscience Teaching and Research Fund (MNTRF) and Marker Diagnostics. The NIHR, MRC and MNTRF had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. This study was supported by the National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre (NIHR SRMRC). The views expressed are those of the authors and not necessarily those of the NIHR, the Department of Health and Social Care or the other funders.
Data availability statement:
Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Deidentified participant data available on request. Please contact the corresponding authors at the following address: v.dipietro@bham.ac.uk; a.belli@bham.ac.uk.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Objective: To investigate the role of salivary small non-coding RNAs (sncRNAs) in the diagnosis of sport-related concussion. Methods: Saliva was obtained from male professional players in the top two tiers of England's elite rugby union competition across two seasons (2017-2019). Samples were collected preseason from 1028 players, and during standardised head injury assessments (HIAs) at three time points (in-game, post-game, and 36-48 hours post-game) from 156 of these. Samples were also collected from controls (102 uninjured players and 66 players sustaining a musculoskeletal injury). Diagnostic sncRNAs were identified with next generation sequencing and validated using quantitative PCR in 702 samples. A predictive logistic regression model was built on 2017-2018 data (training dataset) and prospectively validated the following season (test dataset). Results: The HIA process confirmed concussion in 106 players (HIA+) and excluded this in 50 (HIA-). 32 sncRNAs were significantly differentially expressed across these two groups, with let-7f-5p showing the highest area under the curve (AUC) at 36-48 hours. Additionally, a combined panel of 14 sncRNAs (let-7a-5p, miR-143-3p, miR-103a-3p, miR-34b-3p, RNU6-7, RNU6-45, Snora57, snoU13.120, tRNA18Arg-CCT, U6-168, U6-428, U6-1249, Uco22cjg1,YRNA_255) could differentiate concussed subjects from all other groups, including players who were HIA- and controls, immediately after the game (AUC 0.91, 95% CI 0.81 to 1) and 36-48 hours later (AUC 0.94, 95% CI 0.86 to 1). When prospectively tested, the panel confirmed high predictive accuracy (AUC 0.96, 95% CI 0.92 to 1 post-game and AUC 0.93, 95% CI 0.86 to 1 at 36-48 hours). Conclusions: SCRUM, a large prospective observational study of non-invasive concussion biomarkers, has identified unique signatures of concussion in saliva of male athletes diagnosed with concussion.
AB - Objective: To investigate the role of salivary small non-coding RNAs (sncRNAs) in the diagnosis of sport-related concussion. Methods: Saliva was obtained from male professional players in the top two tiers of England's elite rugby union competition across two seasons (2017-2019). Samples were collected preseason from 1028 players, and during standardised head injury assessments (HIAs) at three time points (in-game, post-game, and 36-48 hours post-game) from 156 of these. Samples were also collected from controls (102 uninjured players and 66 players sustaining a musculoskeletal injury). Diagnostic sncRNAs were identified with next generation sequencing and validated using quantitative PCR in 702 samples. A predictive logistic regression model was built on 2017-2018 data (training dataset) and prospectively validated the following season (test dataset). Results: The HIA process confirmed concussion in 106 players (HIA+) and excluded this in 50 (HIA-). 32 sncRNAs were significantly differentially expressed across these two groups, with let-7f-5p showing the highest area under the curve (AUC) at 36-48 hours. Additionally, a combined panel of 14 sncRNAs (let-7a-5p, miR-143-3p, miR-103a-3p, miR-34b-3p, RNU6-7, RNU6-45, Snora57, snoU13.120, tRNA18Arg-CCT, U6-168, U6-428, U6-1249, Uco22cjg1,YRNA_255) could differentiate concussed subjects from all other groups, including players who were HIA- and controls, immediately after the game (AUC 0.91, 95% CI 0.81 to 1) and 36-48 hours later (AUC 0.94, 95% CI 0.86 to 1). When prospectively tested, the panel confirmed high predictive accuracy (AUC 0.96, 95% CI 0.92 to 1 post-game and AUC 0.93, 95% CI 0.86 to 1 at 36-48 hours). Conclusions: SCRUM, a large prospective observational study of non-invasive concussion biomarkers, has identified unique signatures of concussion in saliva of male athletes diagnosed with concussion.
KW - brain
KW - concussion
KW - contact sports
KW - diagnosis
KW - trauma
UR - http://www.scopus.com/inward/record.url?scp=85103163050&partnerID=8YFLogxK
U2 - 10.1136/bjsports-2020-103274
DO - 10.1136/bjsports-2020-103274
M3 - Article
AN - SCOPUS:85103163050
SN - 0306-3674
VL - 55
SP - 1395
EP - 1404
JO - British Journal of Sports Medicine
JF - British Journal of Sports Medicine
IS - 24
ER -