Chapter 27 - Rheumatic Fever: How Streptococcal Throat Infection Triggers an Autoimmune Disease

Abstract

Molecular mimicry between streptococcal and human proteins has been proposed as the triggering factor leading to autoimmunity in rheumatic fever (RF) and rheumatic heart disease (RHD). Punctual genetic polymorphisms related to both innate and adaptive immune responses are involved in the development of RF/RHD. Some adhesion molecules and chemokines facilitate the monocytes and macrophages and T and B cell infiltration to the heart-tissue. Here we presented data on molecular mimicry mediated by B and T cell responses of peripheral blood and T cell clones infiltrating heart lesions from RHD patients against streptococcal antigens and human tissue proteins. The molecular analysis of T cell recognition is assessed by the definition of heart-cross reactive antigens. Degenerate patterns of T cell receptor (TCR) recognition in which intralesional T cell clones presenting the same TCR-BVJB and AVJB and recognized different antigens are described. The production of inflammatory cytokines such as TNFa, IL-2, IL-17, IL-23 and IFNg from peripheral and heart-infiltrating mononuclear cells, suggested that Th-1 and Th-17 type cytokines are the mediators of RHD heart lesions. All the results presented here delineate the mechanisms involved in RF/RHD and can certainly be a model for other autoimmune diseases.