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Rheumatic fever and rheumatic heart disease: genetics and pathogenesis Guilherme L; Ramasawmy R; Kalil JScand J Immunol 2007[Aug]; 66 (2-3): 199-207Molecular mimicry between streptococcal and human proteins is considered as the triggering factor leading to autoimmunity in rheumatic fever (RF) and rheumatic heart disease (RHD). Here, we present a review of the genetic susceptibility markers involved in the development of RF/RHD and the major immunopathological events underlying the pathogenesis of RF and RHD. Several human leucocyte antigen (HLA) class II alleles are associated with the disease. Among these alleles, HLA-DR7 is predominantly observed in different ethnicities and is associated with the development of valvular lesions in RHD patients. Cardiac myosin is one of the major autoantigens involved in rheumatic heart lesions and several peptides from the LMM (light meromyosin) region were recognized by peripheral and intralesional T-cell clones from RF and RHD patients. The production of TNF-alpha and IFN-gamma from heart-infiltrating mononuclear cells suggests that Th-1 type cytokines are the mediators of RHD heart lesions while the presence of few interleukin-4 producing cells in the valve tissue contributes to the maintenance and progression of the valvular lesions.|Amino Acid Sequence[MESH]|Animals[MESH]|Autoimmune Diseases/genetics/metabolism/pathology[MESH]|Humans[MESH]|Molecular Sequence Data[MESH]|Rheumatic Fever/*genetics/*immunology/metabolism/pathology[MESH]|Rheumatic Heart Disease/*genetics/*immunology/metabolism/pathology[MESH] |
