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Unique diagnostic signatures of concussion in the saliva of male athletes: the Study of Concussion in Rugby Union through MicroRNAs (SCRUM)

Published version
Peer-reviewed

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Authors

Di Pietro, Valentina  ORCID logo  https://orcid.org/0000-0001-9430-4723
O'Halloran, Patrick 
Watson, Callum N 
Begum, Ghazala 
Acharjee, Animesh 

Abstract

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.

Description

Funder: Medical Research Council; FundRef: http://dx.doi.org/10.13039/501100000265


Funder: National Institute for Health Research; FundRef: http://dx.doi.org/10.13039/501100000272


Funder: Marker Diagnostics


Funder: Rugby Football Union


Funder: Midland Neuroscience Teaching and Research Fund

Keywords

Original research, 1506, 1612, 2314, trauma, concussion, brain, contact sports, diagnosis

Journal Title

British Journal of Sports Medicine

Conference Name

Journal ISSN

0306-3674
1473-0480

Volume Title

Publisher

BMJ Publishing Group