McMillan David J, Rafeek Rukshan A M, Norton Robert E, Good Michael F, Sriprakash Kadaba S, Ketheesan Natkunam
School of Science and Technology, Engineering and Genecology Research Centre, University of the Sunshine Coast, Maroochydore, QLD, Australia.
School of Science and Technology, University of New England, Armidale, NSW, Australia.
Front Cardiovasc Med. 2021 May 14;8:674805. doi: 10.3389/fcvm.2021.674805. eCollection 2021.
Current diagnosis of Acute Rheumatic Fever and Rheumatic Heart Disease (ARF/RHD) relies on a battery of clinical observations aided by technologically advanced diagnostic tools and non-specific laboratory tests. The laboratory-based assays fall into two categories: those that (1) detect "evidence of preceding streptococcal infections" (ASOT, anti-DNAse B, isolation of the Group A from a throat swab) and (2) those that detect an ongoing inflammatory process (ESR and CRP). These laboratory tests are positive during any streptococcal infection and are non-specific for the diagnosis of ARF/RHD. Over the last few decades, we have accumulated considerable knowledge about streptococcal biology and the immunopathological mechanisms that contribute to the development, progression and exacerbation of ARF/RHD. Although our knowledge is incomplete and many more years will be devoted to understanding the exact molecular and cellular mechanisms involved in the spectrum of clinical manifestations of ARF/RHD, in this commentary we contend that there is sufficient understanding of the disease process that using currently available technologies it is possible to identify pathogen associated peptides and develop a specific test for ARF/RHD. It is our view that with collaboration and sharing of well-characterised serial blood samples from patients with ARF/RHD from different regions, antibody array technology and/or T-cell tetramers could be used to identify streptococcal peptides specific to ARF/RHD. The availability of an appropriate animal model for this uniquely human disease can further facilitate the determination as to whether these peptides are pathognomonic. Identification of such peptides will also facilitate testing of potential anti-streptococcal vaccines for safety and avoid potential candidates that may pre-dispose potential vaccine recipients to adverse outcomes. Such peptides can also be readily incorporated into a universally affordable point of care device for both primary and tertiary care.
目前，急性风湿热和风湿性心脏病（ARF/RHD）的诊断依赖于一系列临床观察，并借助技术先进的诊断工具和非特异性实验室检查。基于实验室的检测可分为两类：一类是检测“先前链球菌感染的证据”（抗链球菌溶血素O、抗脱氧核糖核酸酶B、从咽拭子中分离出A组链球菌），另一类是检测正在进行的炎症过程（红细胞沉降率和C反应蛋白）。这些实验室检查在任何链球菌感染期间都会呈阳性，对ARF/RHD的诊断并无特异性。在过去几十年里，我们积累了大量关于链球菌生物学以及导致ARF/RHD发生、发展和加重的免疫病理机制的知识。尽管我们的知识尚不完整，还需要很多年才能完全理解ARF/RHD临床表现谱中确切的分子和细胞机制，但在本评论中，我们认为对疾病过程已有足够的了解，利用现有技术有可能识别病原体相关肽，并开发出针对ARF/RHD的特异性检测方法。我们认为，通过合作并共享来自不同地区ARF/RHD患者特征明确的系列血样，抗体芯片技术和/或T细胞四聚体可用于识别ARF/RHD特有的链球菌肽。针对这种独特的人类疾病建立合适的动物模型，可进一步有助于确定这些肽是否具有致病性。识别此类肽还将有助于检测潜在抗链球菌疫苗的安全性，并避免可能使潜在疫苗接种者易出现不良后果的候选疫苗。此类肽还可很容易地整合到一种普遍适用且价格亲民的基层和三级医疗即时检测设备中。
