Febre reumatica

PERSPECTIVES
OPINION

Revisiting the pathogenesis of rheumatic fever and carditis
Rajendra Tandon, Meenakshi Sharma, Y. Chandrashekhar, Malak Kotb,
Magdi H. Yacoub and Jagat Narula
Abstract | Rheumatic fever is one of the most-neglected ailments, and its pathogenesis remains poorly understood. The major thrust of research has been directed towards cross-reactivity between streptococcal M protein and myocardial α‑helical coiled-coil proteins. M protein has also been the focus of vaccine development. The characteristic pathological findings suggest that the primary site of rheumatic-fever-related damage is subendothelial and perivascular connective tissue matrix and overlying endothelium. Over the past 5 years, a streptococcal M protein
N‑terminus domain has been shown to bind to the CB3 region in collagen type IV. This binding seems to initiate an antibody response to the collagen and result in ground substance inflammation. These antibodies do not cross-react with M proteins, and we believe that no failure of immune system and, possibly, no molecular mimicry occur in rheumatic fever. This alternative hypothesis shares similarity with collagen involvement in both Goodpasture syndrome and Alport syndrome.
Tandon, R. et al. Nat. Rev. Cardiol. 10, 171–177; published online 15 January 2013; doi:10.1038/nrcardio.2012.197 Introduction
Rheumatic heart disease is known to affect
15 million individuals worldwide;1,2 how­ ever, systematic echocardiographic screen­ ing in endemic areas indicates that this figure is a gross underestimation. 3,4 No effective methods for primary prevention or specific medical therapy are currently avail­ able, because the pathogenesis of rheuma­ tic fever remains poorly understood. The pathogenesis of this condition is believed to involve cross reactivity between various moieties in the causative strepto­ occus c strain and numerous cardiac antigenic epitopes; the most-discussed molecular mimicry has