ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Streptococcal antigens induce autoimmune carditis and neurobehavioral changes – implications for rheumatic heart disease diagnosis and prevention (#244)

Rukshan Ahamed Mohamed Rafeek 1 , Adam S Hamlin 1 , Nicholas M Andronicos 1 , David J McMillan 2 , Kadaba S Sriprakash 3 , Natkunam Ketheesan 1
  1. School of Science and Technology, University of New England, Armidale, NSW, Australia
  2. School of Science, Technology, Engineering and Genecology Research Centre, University of the Sunshine Coast, Maroochydore, Queensland, Australia
  3. Institute for Biomedicine and Glycomics, Griffith University, Gold Coast, Queensland, Australia

Background: The pathogenesis of Acute Rheumatic Fever/Rheumatic Heart Disease (ARF/RHD) and associated neurobehavioral disorders is complex. An autoimmune response triggered by group A streptococcal (GAS) infection elicits antibodies that cross-reacts with the pathogen and host proteins leading to cardiac tissue damage and neurobehavioral changes. Because throat carriage of GAS has been reported to be relatively low in some ARF/RHD endemic regions as opposed to Streptococcus dysgalactiae subspecies equisimilis (SDSE), we hypothesised that streptococci other than GAS may also be associated with the development of ARF/RHD and associated neurobehavioral disorders.

Methods: Lewis rats were injected with recombinant GAS and SDSE M proteins. Standard neurobehavioral assessments and electrocardiography were performed for both pre and post streptococcal antigen exposed groups. ELISA and Western blot analysis were performed to determine the cross reactivity of antibodies with host connective tissue, cardiac and neuronal proteins. Histological assessments were performed to confirm inflammatory changes in cardiac and neuronal tissue.

Results: Lewis rats exposed to both GAS and SDSE antigens developed significant cardiac functional and neurobehavioral abnormalities compared to control animal injected with PBS. Antibodies against GAS and SDSE antigens cross-reacted with cardiac myosin, collagen, tropomycin, laminin, lysoganglioside, tubulin, dopamine 1 and dopamine 2 receptors. The specificity of the cross-reactive anti-GAS and anti-SDSE antibody responses with endogenous host antigens were further confirmed by Western blot analysis.   

Conclusion: Cardiac and neurobehavioral changes observed in our experimental model exposed to GAS and SDSE antigens were comparable to human disease and demonstrated for the first time that antigen from a streptococcal species other than GAS can initiate and drive the autoimmune responses that cause cardiac and neurobehavioral changes. This study has contributed to the understanding of the early events following streptococcal antigen exposure leading to carditis and neurobehavioral changes thereby bridging the gap between preclinical observations and clinical practice.