Oral Presentation Lancefield International Symposium for Streptococci and Streptococcal Diseases 2025

A peptide epitope biomarker signature that differentiates acute rheumatic fever from related clinical presentations (118534)

Tim Barnett 1 2 , Luke Marshall 3 , Soraya Leedham 3 , Paige Warburton 3 , Monika Tschochner 3 , Reuben McGregor 4 5 , Anna Ralph 6 , Rachel Webb 7 8 9 , Emmy Okello 10 11 , Andrea Beaton 12 13 , Jonathan Carapetis 14 , Nikki Moreland 4 5 , Mark Davies 15 , Samuel Lundin 3
  1. Wesfarmers Centre for Vaccines and Infectious Diseases, The Kids Research Institute Australia, Nedlands, WA, Australia
  2. School of Biomedical Sciences, The University of Western Australia, Nedlands, WA, Australia
  3. Biotome Pty Ltd, Nedlands, WA, Australia
  4. School of Medical Science, The University of Auckland, Auckland, New Zealand
  5. Maurice Wilkins Centre for Biodiscovery, The University of Auckland, Auckland, New Zealand
  6. Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
  7. KidzFirst Children’s Hospital, Health New Zealand – Te Whatu Ora, Auckland, New Zealand
  8. Starship Children’s Hospital, Health New Zealand – Te Whatu Ora, Auckland, New Zealand
  9. Department of Paediatrics, Child and Youth Health, The University of Auckland, Auckland, New Zealand
  10. The Uganda Heart Institute, Mulago Hospital Complex, Kampala, Uganda
  11. Department of Medicine, Makerere University, Kampala, Uganda
  12. Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
  13. Department of Pediatrics, The University of Cincinnati School of Medicine, Cincinnati, OH, USA
  14. Telethon Kids Institute and the University of Western Australia, Nedlands, WA, Australia
  15. Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia

BACKGROUND
Streptococcus pyogenes (Group A Streptococcus, GAS) causes throat infections which can lead to a systemic inflammatory disorder called acute rheumatic fever (ARF). Early ARF diagnosis is vital to avoid permanent damage to the heart valves called rheumatic heart disease (RHD). While ARF mostly occurs in children aged 5–14 years, RHD has lifelong effects on quality of life and productivity. ARF diagnosis relies on clinical criteria and demonstrating a temporally-associated GAS infection. However, serology based on the conserved GAS antigens streptolysin O and DNAse B is complicated in endemic disease settings due to very high rates of superficial GAS infections.

METHODS
We investigated whether GAS strain-specific linear antibody epitopes could improve ARF diagnosis, using a combination of comparative genomics and high-density peptide microarray profiling. We screened IgG- and IgA-binding to 41,600 sequence-overlapping 12-mer peptides from 1,100 GAS proteins, using pooled serum samples from ARF cases or healthy controls. Identified epitopes (n=1,200) were further tested using individual serum/plasma samples (n=300) from three different study cohorts that included ARF cases, individuals with clinically-similar conditions, and healthy controls.

RESULTS
We identified a panel of linear epitopes (n=12) that provided good discrimination between ARF patients and clinically-similar conditions (ROC-AUC > 0.85).

CONCLUSION
While our findings require further validation, they highlight the potential for epitope specific serology to identify clinically useful biomarkers that could improve detection of ARF-associated GAS infections.