The diagnosis and management of concussion is hindered by its diverse clinical presentation and assessment tools reliant on subjectively experienced symptoms. The biomechanical threshold of concussion is also not well understood, and asymptomatic concussion 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 neuroinflammatory mechanisms may serve an important role subsequent to concussion and possibly to subconcussive impacts. These studies suggest that autoantibodies may be a valuable tool for detection of acute concussion and monitoring for changes caused by cumulative exposure to subconcussive impacts. Hence, we aimed to profile the immunoglobulin (Ig)A 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 (24–48 h 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 whether cohorts showed similarities. The results show a significant increase in the prevalence of IgA toward protein fragments representing 5-hydroxytryptamine receptor 1A (HTR1A), serine/arginine repetitive matrix 4 (SRRM4) and FAS (tumor necrosis factor receptor superfamily member 6) 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.

中文翻译：

---

急性脑震荡和亚脑震荡后运动员唾液中富含脑和凋亡调节蛋白的免疫球蛋白 A 自身反应性

脑震荡的诊断和管理受到其依赖于主观体验症状的多样化临床表现和评估工具的阻碍。脑震荡的生物力学阈值也不是很清楚，无症状脑震荡或不同幅度的“亚脑震荡”在接触性运动中很常见。由于运动员过早恢复活动会增加长期恢复或长期不良健康后果的风险，因此人们越来越担心。迄今为止，关于震荡和次震荡影响的分子水平知之甚少。最近的研究表明，神经炎症机制可能在脑震荡和亚脑震荡后发挥重要作用。这些研究表明，自身抗体可能是检测急性脑震荡和监测亚脑震荡累积暴露引起的变化的宝贵工具。因此，我们旨在通过筛选独特的运动相关头部创伤生物库来分析唾液中的免疫球蛋白 (Ig)A 自身抗体库。唾液样本 (n = 167) 由参加脑震荡（受伤后 24-48 小时）或脑震荡（非脑震荡参与者具有中度或高度累积次脑震荡影响）队列的男性和女性参与者捐赠。研究设计包括发现和验证阶段。发现旨在确定 IgA 的新候选自身免疫靶点。验证测试了脑震荡和亚脑震荡队列是否增加了 IgA 反应性以及队列是否显示出相似性。结果显示，在脑震荡和脑震荡后，IgA 对代表 5-羟色胺受体 1A (HTR1A)、丝氨酸/精氨酸重复基质 4 (SRRM4) 和 FAS（肿瘤坏死因子受体超家族成员 6）的蛋白质片段的流行显着增加。这些结果可能表明脑震荡和亚脑震荡会引起相似的生理效应，尤其是在免疫反应方面。我们的研究表明，唾液是用于脑震荡和脑震荡下的自身抗体检测的潜在生物流体。在更大的独立研究集中经过严格确认后，经过验证的唾液自身抗体测定可以提供评估震荡和亚震荡事件的非主观定量方法。