Rheumatic fever revisited

Abstract

In their Perspectives article (Tandon, R. et al. Revisiting the pathogenesis of rheumatic fever and carditis. Nat. Rev. Cardiol. 10, 171–177 [2013]),1 Tandon et al. provide a very thoughtful analysis and review of the pathogenesis of acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Their views challenge the role of molecular mimicry in rheumatic carditis. For years, two groups of thought have existed, one proposing molecular mimicry between streptococcus and the heart, and the other proposing collagen-mediated disease in the valve. Both could be correct and are supported by data indicating elevation of anticollagen and anti-cardiac-myosin antibody responses in rheumatic carditis.2 These two hypotheses are important, but one hypothesis does not exclude the other. Most autoimmune diseases involve more than one autoantigen,3 and both cardiac myosin and collagen are autoantigens in RHD,2 and one might precede the other. ARF and RHD develop over time from multiple streptococcal infections4 leading to the production of IgG autoantibodies of relatively high avidity. This pathophysiology does not occur as a result of gross immaturity of the immune system, as suggested by Tandon and colleagues, but because of the continual streptococcal infections that maintain the germinal centre reaction and affinity maturation of antibody. Earlier this year, Zhang et al. proposed that antibody feeds back and stops the germinal centre reaction in the normal immune response.5 However, in ARF and RHD, high levels of immune complexes would capture antibodies of higher affinity and allow the germinal centres to continue to feed highaffinity autoantibody specificities into the blood, which would eventually cause damage to the valve. When levels of antibodies against streptococcal group A carbohydrate continue to elevate during ARF and RHD, prognosis is poor. Only upon valve replacement do the levels of autoantibody against the valve and group A carbohydrate subside concomitantly with healing and restoration of heart function.6 Anti-group A Rheumatic fever revisited

DOI: 10.1038/nrcardio.2012.197-c1

Cite this paper

@article{Cunningham2014RheumaticFR, title={Rheumatic fever revisited}, author={Madeleine W. Cunningham}, journal={Nature Reviews Cardiology}, year={2014}, volume={11}, pages={123-123} }