Group A streptococci (GAS) has the potential to initiate an autoimmune process leading to acute rheumatic fever (ARF) and rheumatic heart disease (RHD). GAS infections can also trigger acute post-streptococcal glomerulonephritis (APSGN) leading to chronic kidney failure (CKD). Due to the inability to determining the early events that lead to these chronic conditions, both clinicians and researchers have long recognised the need for small laboratory animal models that mimic the human disease.
Using the rat autoimmune valvulitis model (RAV), we determined kinetics of specific antibodies and T cells during the early to late phase (35-210 days post exposure to GAS rM5) in inducing the cardiac damage. A series of preliminary studies were conducted on Lewis rats to determine how selected GAS proteins cause renal pathology.
Lewis rats injected with GAS M proteins developed significant cardiac functional and neurobehavioral abnormalities in comparison to control rats injected with PBS. Serum from rats injected with M protein cross-reacted with purified cardiac, connective and neuronal proteins. We have observed a dysregulation of T cells, including GAS M protein induced interleukin 17A/interferon γ- mediated tissue damage, a feature of ARF/RHD.
Our investigations have identified the immunopathological events leading to initial antibody production and T cell activation and subsequent cardiac damage. The development of the RAV model has enabled to: (1) assess the safety of anti-streptococcal vaccine candidates; (2) identify specific biomarkers for point-of-care screening tests and (3) develop next generation immunotherapies. Preliminary results from our APSGN study are inconclusive and may indicate the involvement of multiple GAS proteins in the development of kidney pathology.