Pin E, Petricoin E, Cortes N, Bowman T, Andersson E, Uhlen M, Nilsson P, Caswell SV
J. Neurotrauma - (-) - [2021-04-15; online 2021-04-15]
The diagnosis and management of concussion is hindered by its diverse clinical presentation and assessment tools reliant upon subjectively-experienced symptoms. The biomechanical threshold of concussion is also not well understood and asymptomatic or 'subconcussive impacts' of variable magnitudes are common in contact sports. Concerns have risen because athletes returning to activity too soon have an increased risk of prolonged recovery or long-term adverse health consequences. To date, little is understood on a molecular level regarding concussion and subconcussive impacts. Recent research suggests that neuro-inflammatory mechanisms may serve an important role subsequent to concussion and possibly subconcussive impacts. These studies suggest that autoantibodies may be a feasible method of detection for acute concussion and monitoring for changes due to cumulative exposure to subconcussive impacts. Hence, we aimed to profile the IgA autoantibody repertoire in saliva by screening a unique sport-related head trauma biobank. Saliva samples (N=167) were donated by male and female participants enrolled in either the Concussion (24 to 48 hours post-injury) or Subconcussion (non-concussed participants having moderate or high cumulative subconcussive impact exposure) Cohorts. Study design included discovery and verification phases. Discovery aimed to identify new candidate autoimmune targets of IgA. Verification tested whether Concussion and Subconcussion Cohorts increased IgA reactivity and cohorts showed similarities. In each phase, sample testing was randomized. The results show a significant increase in the prevalence of IgA towards protein fragments representing HTR1A, SRRM4 and FAS after concussion and subconcussion. These results may suggest that concussion and subconcussion induce similar physiological effects, especially in terms of immune response. Our study demonstrates that saliva is a potential biofluid for autoantibody detection in concussion and subconcussion. After rigorous confirmation in much larger independent study sets, a validated salivary autoantibody assay could provide a non-subjective quantitative means of assessing concussive and subconcussive events.
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