Protobios Llc, Mäealuse 4, 12618, Tallinn, Estonia.
Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, 12618, Tallinn, Estonia.
Commun Biol. 2022 Mar 4;5(1):205. doi: 10.1038/s42003-022-03122-4.
Cumulative evidence over the last decades have supported the role of gum infections as a risk for future major cardiovascular events. The precise mechanism connecting coronary artery disease (CAD) with periodontal findings has remained elusive. Here, we employ next generation phage display mimotope-variation analysis (MVA) to identify the features of dysfunctional immune system that associate CAD with periodontitis. We identify a fine molecular description of the antigenic epitope repertoires of CAD and its most severe form - acute coronary syndrome (ACS) by profiling the antibody reactivity in a patient cohort with invasive heart examination and complete clinical oral assessment. Specifically, we identify a strong immune response to an EBV VP26 epitope mimicking multiple antigens of oral biofilm as a biomarker for the no-CAD group. With a 2-step biomarker test, we stratify subjects with periodontitis from healthy controls (balanced accuracy 84%), and then assess the risk for ACS with sensitivity 71-89% and specificity 67-100%, depending on the oral health status. Our findings highlight the importance of resolving the immune mechanisms related to severe heart conditions such as ACS in the background of oral health. Prospective validation of these findings will support incorporation of these non-invasive biomarkers into clinical practice.
过去几十年的累积证据支持了牙龈感染是未来发生重大心血管事件的风险因素。将冠状动脉疾病(CAD)与牙周病发现联系起来的确切机制仍难以捉摸。在这里,我们采用下一代噬菌体展示模拟表位变异分析(MVA)来识别与牙周炎相关的 CAD 及最严重形式 - 急性冠脉综合征(ACS)的功能失调免疫系统的特征。我们通过对接受侵袭性心脏检查和完整临床口腔评估的患者队列进行抗体反应分析,对 CAD 及其最严重形式 - 急性冠脉综合征(ACS)的抗原表位库进行了精细的分子描述。具体而言,我们发现针对 EBV VP26 表位的强烈免疫反应,该表位模拟口腔生物膜的多种抗原,是无 CAD 组的生物标志物。通过两步生物标志物测试,我们对牙周炎患者进行分层,将其与健康对照组进行区分(平衡准确性为 84%),然后根据口腔健康状况,以 71-89%的敏感性和 67-100%的特异性来评估 ACS 的风险。我们的研究结果强调了解决与 ACS 等严重心脏疾病相关的免疫机制的重要性,而这些机制在口腔健康的背景下发生。对这些发现进行前瞻性验证将支持将这些非侵入性生物标志物纳入临床实践。