Utility of Human Immune Responses to GAS Antigens as a Diagnostic Indicator for ARF: A Systematic Review

Abstract

Background: 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.Methods: 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).Results and Conclusion: The search strategy yielded 534 studies, from which 24 met the inclusion criteria, reporting on evaluation of titers for SLO (n = 10), DNase B (n = 9), anti-streptokinase (ASK) (n = 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.

Serum Immune Responses to Group A Streptococcal Antigens following Pharyngeal Acquisitions among Children in Cape Town, South Africa

“…In the current study, 60% of the participants in groups 1 and 3 demonstrated antibody increases against either SLO or DNaseB, which is similar to the 67% observed in the previous study. While there is not a standardized ELISA for new immune responses to SLO and DNaseB, these results confirm previous observations showing the relatively low sensitivity of these antibody responses in detecting prior Strep A infection ( 8 , 15 , 23 ). This study also highlights the usefulness of employing a change in the antibody response from one time point to the next for accurately describing a positive association with a particular antigen.…”

American Heart Association's Children's Strategically Focused Research Network Experience

“…Nearly a century after AHA began and half a century after commissioning of Cardiovascular Disease in the Young, the Children's Strategically Focused Research Network (SFRN) was established to apply state‐of‐the‐art basic, clinical, and population science strategies and train the next generation of pediatric cardiology scientists while still embodying Cardiovascular Disease in the Young's original focus on RHD, CHD, and preventive cardiology. The Children's SFRN directly and proudly builds on work done by the early pioneers in of pediatric cardiovascular science within AHA in the 1940s and 1950s.This article highlights the hypotheses, goals, accomplishments, challenges, and future directions of each center; provides an overview of collaboration efforts (Table 1 ) 1 , 2 , 3 , 4 and trainee accomplishments (Table 2 ) 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ; and summarizes how we can leverage the output of this SFRN to advance pediatric cardiovascular science.…”