Poster Presentation Lancefield International Symposium for Streptococci and Streptococcal Diseases 2025

The longitudinal characterisation of immune responses in the Rat Autoimmune Valvulitis model enables the assessment of disease severity and the identification of biomarkers for ARF/RHD screening (#260)

Rukshan Ahamed Mohamed Rafeek 1 , Mohammad Raguib Munif 1 , Robert A Hart 1 , Ailin Lepletier 2 , David McMillan 3 , Manisha Pandey 2 , Michael F Good 2 , Natkunam Ketheesan 1
  1. School of Science and Technology, University of New England, Armidale, NSW, Australia
  2. Institute for Biomedicine and Glycomics, Griffith University, Gold Coast, Queensland, Australia
  3. School of Science, Technology, Engineering and Genecology Research Centre, University of Sunshine Coast , Sunshine Coast, Queensland, Australia

Acute rheumatic fever (ARF) is an autoimmune disorder triggered by group A streptococcal (GAS) throat and/or skin infections that can lead to rheumatic heart disease (RHD). Understating the immune response to GAS M protein, which is one of the main contributors to the inflammatory process in ARF/RHD, is essential to determine the pathogenesis, identify molecules for screening and therapeutic targets. In this study, we assessed the cross-reactive antibody levels and T-helper cell (Th) responses at different stages of the disease process in the Rat Autoimmune Valvulitis model.

Lewis rats were injected with recombinant GAS M protein (GAS rM5), and both functional (ECG) and immunohistological studies were conducted to evaluate cardiac pathology. Tissue cross-reactive antibody levels and Th 1 and 17 cell responses were determined by ELISA and flow cytometry analysis respectively at days 7, 14, 21, 28, 35, 70 and 210 post primary injection.

Elevated levels of cross-reactive antibodies, Th1 & Th17 cells and reduced levels of regulatory T-cells were required for the induction of functional and histological changes in the cardiac tissue. The levels of cross-reactive antibodies and Th 1 and 17 cells gradually reduced over the 210 day period post initial injection with rM5. However, when the rats were boosted with an additional GAS rM5 injection on day 204, levels of antibodies and T-cells were further elevated. Therefore, the characterisation of immune responses to GAS rM5 provides a new insight into the role of cross-reactive antibodies and T cells in the pathogenesis and disease progression of ARF/RHD.