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

Research output: Contribution to journalArticlepeer-review

Authors

  • Callum N Watson
  • Ghazala Begum
  • Kamal M Yakoub
  • Conor Bentley
  • Paolo Iliceto
  • Gabriella Candilera
  • David K Menon
  • Matthew J Cross
  • Keith A Stokes
  • Simon Pt Kemp

External organisations

  • Marker Diagnostics UK Limited
  • University Hospital Birmingham
  • S&P Statistics and Psychometrics Ltd
  • University of Cambridge
  • University of Bath
  • Rugby Football Union, London, GB

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.

Bibliographic note

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Details

Original languageEnglish
JournalBritish Journal of Sports Medicine
Early online date23 Mar 2021
Publication statusE-pub ahead of print - 23 Mar 2021