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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\u2010DR7 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\u2010cell clones from RF and RHD patients. The production of TNF\u2010<jats:italic>\u03b1<\/jats:italic> and IFN\u2010<jats:italic>\u03b3<\/jats:italic> from heart\u2010infiltrating mononuclear cells suggests that Th\u20101 type cytokines are the mediators of RHD heart lesions while the presence of few interleukin\u20104 producing cells in the valve tissue contributes to the maintenance and progression of the valvular lesions.<\/jats:p>","DOI":"10.1111\/j.1365-3083.2007.01974.x","type":"journal-article","created":{"date-parts":[[2007,7,16]],"date-time":"2007-07-16T11:48:39Z","timestamp":1184586519000},"page":"199-207","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Rheumatic Fever and Rheumatic Heart Disease: Genetics and Pathogenesis"],"prefix":"10.1111","volume":"66","author":[{"given":"L.","family":"Guilherme","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Ramasawmy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Kalil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,7,16]]},"reference":[{"key":"e_1_2_9_2_2","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1001\/jama.1992.03490150121036","article-title":"Guidelines for the diagnosis of Rheumatic Fever: Jones criteria, 1992 uptade","volume":"268","author":"Dajani AS","year":"1992","journal-title":"JAMA"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1601-0825.2002.1o816.x"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.10.5.699"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(52)90294-5"},{"key":"e_1_2_9_6_2","first-page":"61","article-title":"Possible genetic factors in the etiology of rheumatic fever","volume":"5","author":"Uchida IA","year":"1953","journal-title":"Am J Hum Genet"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.1953.tb02546.x"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM196801252780403"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.5165.21"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780040210"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.5311.1023"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1973.tb00991.x"},{"key":"e_1_2_9_13_2","first-page":"319","article-title":"HL\u2010A antigens in Europeans and Maoris with rheumatic fever and rheumatic heart disease","volume":"2","author":"Caughey DE","year":"1975","journal-title":"J Rheumatol"},{"key":"e_1_2_9_14_2","first-page":"84","article-title":"Parallel studies of HLA antigens in patients with rheumatic heart disease and scleritis: comparisons with three control populations","volume":"3","author":"Joysey VC","year":"1977","journal-title":"J Rheumatol Suppl"},{"key":"e_1_2_9_15_2","first-page":"506","article-title":"Rheumatic fever and its sequels in children. 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