Abstract
Rheumatic fever (RF) is an autoimmune disease which affects more than 20 million children in developing countries. It is triggered by Streptococcus pyogenes throat infection in untreated susceptible individuals. Carditis, the most serious manifestation of the disease, leads to severe and permanent valvular lesions, causing chronic rheumatic heart disease (RHD). We have been studying the mechanisms leading to pathological autoimmunity in RF/RHD for the last 15 years. Our studies allowed us a better understanding of the cellular and molecular pathogenesis of RHD, paving the way for the development of a safe vaccine for a post-infection autoimmune disease. We have focused on the search for protective T and B cell epitopes by testing 620 human blood samples against overlapping peptides spanning 99 residues of the C-terminal portion of the M protein, differing by one amino acid residue. We identified T and B cell epitopes with 22 and 25 amino acid residues, respectively. Although these epitopes were from different regions of the C-terminal portion of the M protein, they showed an identical core of 16 amino acid residues. Antibodies against the B cell epitope inhibited bacterial invasion/adhesion in vitro. Our results strongly indicated that the selected T and B cell epitopes could potentially be protective against S. pyogenes.
Highlights
Rheumatic fever (RF) is a post-infectious autoimmune disease which affects over 20 million children worldwide, most of which are from developing countries
Our studies have focused on the search for protective T and B cell epitopes by using a large panel of human blood samples, tested against overlapping peptides derived from the C-terminal portion of the streptococcal M protein differing by only one amino acid residue
Aiming to find a common streptococcal epitope able to induce the production of antibodies in healthy individuals as well as in RF patients, we evaluated the IgG response of 250 serum samples to 79 overlapping C-terminal streptococcal M protein peptides (Figure 2)
Summary
Rheumatic fever (RF) is a post-infectious autoimmune disease which affects over 20 million children worldwide, most of which are from developing countries. This disease affects 3– 4% of untreated susceptible individuals infected by Streptococcus pyogenes. RHD continues to be a major public health problem in developing countries, leading to 233,000 deaths/ year (Carapetis et al 2005a,b). The incidence of RHD in the world is at least 15.6 million cases and the highest documented prevalence of the disease among children from developing countries is 5.7 per 1000 in sub-Saharan Africa (Carapetis et al 2005a,b). In Brazil, the incidence of acute rheumatic fever (ARF) has decreased by 75% in the last 10 years, it is still high, reaching 5000 new cases/year (data from the Brazilian Health Ministry)
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