Introduction: Acute rheumatic fever and rheumatic heart disease (ARF/RHD) have long been described as autoimmune sequelae of Streptococcus pyogenes or group A streptococcal (GAS) infection. Although in some ARF/RHD endemic regions, Streptococcus dysgalactiae subspecies equisimilis (SDSE), also known as β-hemolytic groups C and G streptococci (GCS/GGS) have been implicated in the pathogenesis of ARF/RHD, to date there has been no experimental evidence supporting this proposition.
Methods: We used the Rat Autoimmune Valvulitis (RAV) model to investigate multiple mechanisms involved in initiating and potentiating cardiac damage including the potential of streptococci other than GAS contributing to the development of ARF/RHD.
Results: We discovered that GGS does indeed cause both myocarditis and valvulitis, hallmarks of ARF/RHD. Furthermore histological, immunological, echocardiographic and electrocardiographic changes in the hearts of rats exposed to GGS were identical to those exposed to GAS. T and B cell responses and antibody cross-reactivity to cardiac myosin were comparable in both GGS and GAS exposed animals providing additional evidence that GGS can induce and/or exacerbate ARF/RHD.
Discussion: Our experimental observations confirm that repetitive infections with GAS and/or GGS have the potential to initiate and/or exacerbate ARF/RHD. Therefore, ARF/RHD should no longer be described as a disease solely triggered by GAS infection.