title: Rheumatic heart disease: mediation by complex immune events.
abstract: Rheumatic fever (RF) is an autoimmune disease caused by the Gram-positive bacteria Streptococcus pyogenes following an untreated throat infection in susceptible children. Rheumatic heart disease (RHD), the most serious complication, occurs in 30-45% of RF patients and leads to chronic valvular lesions. Here, we focus on the genes that confer susceptibility for developing this disease. Molecular mimicry mediates the cross-reactions between streptococcal antigens and human proteins. Several autoantigens have been identified, including cardiac myosin epitopes, vimentin, and other intracellular proteins. In heart tissue, antigen-driven oligoclonal T cell expansions probably cause the rheumatic heart lesions. These cells are CD4+ and produce inflammatory cytokines (TNF alpha and IFN gamma). IL-4+ cells are found in the myocardium; however, these cells are very scarce in the valve lesions of RHD patients. IL-4 is a Th2-type cytokine and plays a regulatory role in the inflammatory response mediated by Th1 cytokines. Our findings indicate that the Th1/Th2 cytokine balance has a role in healing myocarditis while the low numbers of IL-4-producing cells in the valves probably induced the progressive and permanent valve damage.
authors.affiliation: Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil. luizagui@usp.br
authors.forename: L
authors.initials: L
authors.lastname: Guilherme
authors.forename: K F
authors.initials: KF
authors.lastname: Köhler
authors.forename: J
authors.initials: J
authors.lastname: Kalil
mesh_terms: D020022:Genetic Predisposition to Disease; D006801:Humans; D015847:Interleukin-4 / Q000502:physiology; D018716:Molecular Mimicry; D012214:Rheumatic Heart Disease / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D015847:Interleukin-4