RT Journal Article
SR Electronic
T1 Unique diagnostic signatures of concussion in the saliva of male athletes: the Study of Concussion in Rugby Union through MicroRNAs (SCRUM)
JF British Journal of Sports Medicine
JO Br J Sports Med
FD BMJ Publishing Group Ltd and British Association of Sport and Exercise Medicine
SP 1395
OP 1404
DO 10.1136/bjsports-2020-103274
VO 55
IS 24
A1 Di Pietro, Valentina
A1 O'Halloran, Patrick
A1 Watson, Callum N
A1 Begum, Ghazala
A1 Acharjee, Animesh
A1 Yakoub, Kamal M
A1 Bentley, Conor
A1 Davies, David J
A1 Iliceto, Paolo
A1 Candilera, Gabriella
A1 Menon, David K
A1 Cross, Matthew J
A1 Stokes, Keith A
A1 Kemp, Simon PT
A1 Belli, Antonio
YR 2021
UL http://bjsm.bmj.com/content/55/24/1395.abstract
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.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.