E-Poster with pre-recorded video presentation Lorne Infection and Immunity 2021

Simultaneous Induction of Cardiac and Neurobehavioral Autoimmune Pathology Following Exposure to Streptococcal Antigens (#253)

Rukshan AM 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 Sunshine Coast , Sunshine Coast, Queensland, Australia
  3. Bacterial Pathogenesis Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia

Streptococcal infections constitute more than 700 million cases annually. Repeated or/untreated streptococcal infections lead to post-streptococcal sequelae including Acute Rheumatic Fever, Rheumatic Heart Disease (ARF/RHD) and associated neurobehavioral disorder Sydenham’s Chorea (SC). These autoimmune multisystem disorders are complex and require detailed mechanistic investigations. An animal model, which exhibit both characteristics of cardiac and neurobehavioral defects associated with ARF/RHD, is important for such studies. The objective of this study was to assess the mechanisms including functional and neurobehavioral defects following exposure to streptococcal antigens in a rodent model.

 

Following exposure to Group A streptococcus (GAS) recombinant M5 protein (rM5), whole killed GAS, and recombinant Group G streptococcus M protein (GGS-stg480) we assessed impairments in fine motor control (Food manipulation), gait and balance (beam walking) and obsessive-compulsive behaviour (Grooming and Marble burying). Cardiac tissue damage was assessed by electrocardiography and histology. Rats were euthanised 70 days post exposure; heart and brain were collected for immunopathological analysis and serum assessed for cross-reactivity with cardiac myosin, collagen, tropomycin, laminin, lysogangliosideGM1, dopamine receptors and tubulin.

 

Significant differences were observed in food manipulation (p=0.0086), beam walking (p=0.0101) marble burying (p=0.003) and grooming behaviours (p=<0.0001) in rats injected with streptococcal antigens. In contrast, there were no differences in all of the behavioral tests in control rats. Prolonged P-R intervals were observed in rats injected with streptococcal antigens compared to control rats (p=0.0007). Histological examination of heart sections from these rats demonstrated infiltration of mononuclear cells (carditis score p=<0.0001) and brain sections with deposition of antibodies whereas control rats showed little or no evidence of inflammation.

 

In conclusion, for the first time we have characterised a model that provides longitudinal stability of age-dependent behaviour, to simultaneously investigate both neurobehavioral and cardiac autoimmune abnormalities associated with post streptococcal sequelae.