Salie M Taariq, Rampersadh Kimona, Muhamed Babu, Engel Kélin C, Zühlke Liesl J, Dale James B, Engel Mark E
Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Division of Cardiology, Children's National Health System, Washington, DC, United States.
Front Cardiovasc Med. 2021 Jul 20;8:691646. doi: 10.3389/fcvm.2021.691646. eCollection 2021.
Previous studies have established that streptococcal antibody titer is correlated with a diagnosis of acute rheumatic fever (ARF). However, results vary in the usefulness of GAS antibodies, particularly anti-streptolysin-O (ASO) and anti-DNase B, in confirming a recent GAS infection. Therefore, we sought to provide, from published studies, an evidence-based synthesis of the correlation of streptococcal serology to establish the usefulness of immunological data in aiding the diagnosis of ARF. These findings are anticipated to have implications where echocardiography is not freely available, especially where ARF is rampant. We conducted a comprehensive search across a number of databases. Applying a priori criteria, we selected articles reporting on studies, regardless of study design, that evaluate the levels of antibodies against GAS-specific antigens in ARF subjects against control values or a published standard. Data were extracted onto data extraction forms, captured electronically, and analyzed using Stata software. Risk of bias was assessed in included studies using the Newcastle-Ottawa Scale (NOS). The search strategy yielded 534 studies, from which 24 met the inclusion criteria, reporting on evaluation of titers for SLO ( = 10), DNase B ( = 9), anti-streptokinase (ASK) ( = 3) amongst others. Elevation in titers was determined by comparison with controls and upper limit of normal (ULN) antibody values as determined in healthy individuals. Meta-analysis of case-controlled studies revealed moderate odds ratio (OR) correlations between ARF diagnosis and elevated titers for SLO (OR = 10.57; 95% CI, 3.36-33.29; 10 studies) and DNAse B (OR = 6.97; 95% CI, 2.99-16.27; 7 studies). While providing support for incorporating SLO and DNase B in the diagnosis of ARF, we present the following reflections: an elevation in SLO and DNase B levels are not consistently associated with an ARF diagnosis; increasing the number of GAS proteins in the test is warranted to improve sensitivity; paired (acute and convalescent) samples could provide a more accurate indication of a rising titer. Use of community-based controls as a standard is not a reliable marker by which to gauge recent GAS infection.
以往的研究已经证实，链球菌抗体滴度与急性风湿热（ARF）的诊断相关。然而，A群链球菌（GAS）抗体，特别是抗链球菌溶血素O（ASO）和抗脱氧核糖核酸酶B，在确认近期GAS感染方面的效用结果各不相同。因此，我们试图从已发表的研究中，对链球菌血清学的相关性进行基于证据的综合分析，以确定免疫学数据在辅助ARF诊断中的效用。预计这些发现将对超声心动图无法广泛获取的地区产生影响，尤其是在ARF猖獗的地区。我们在多个数据库中进行了全面搜索。根据预先设定的标准，我们选择了报告研究的文章，无论研究设计如何，这些研究评估了ARF受试者中针对GAS特异性抗原的抗体水平与对照值或已发表标准的比较。数据被提取到数据提取表格上，进行电子记录，并使用Stata软件进行分析。使用纽卡斯尔-渥太华量表（NOS）对纳入研究的偏倚风险进行评估。搜索策略共产生534项研究，其中24项符合纳入标准，报告了对链球菌溶血素O（SLO，n = 10）、脱氧核糖核酸酶B（n = 9）、抗链激酶（ASK，n = 3）等的滴度评估。通过与对照组以及健康个体中确定的正常上限（ULN）抗体值进行比较来确定滴度升高情况。病例对照研究的荟萃分析显示，ARF诊断与SLO滴度升高（比值比[OR] = 10.57；95%置信区间[CI]，3.36 - 33.29；10项研究）和脱氧核糖核酸酶B滴度升高（OR = 6.97；95% CI，2.99 - 16.27；7项研究）之间存在中等程度的OR相关性。在支持将SLO和脱氧核糖核酸酶B纳入ARF诊断的同时，我们提出以下思考：SLO和脱氧核糖核酸酶B水平升高与ARF诊断并非始终相关；有必要增加检测中GAS蛋白的数量以提高敏感性；配对（急性期和恢复期）样本可能会更准确地显示滴度升高情况。将基于社区的对照作为标准并非衡量近期GAS感染的可靠指标。
