{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T19:34:52Z","timestamp":1791833692958,"version":"4.3.4"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,8,28]],"date-time":"2007-08-28T00:00:00Z","timestamp":1188259200000},"content-version":"vor","delay-in-days":88,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:p><jats:bold><jats:sc>Abstract:\u2002<\/jats:sc><\/jats:bold>  <jats:bold>Rheumatic fever (RF) is triggered by <jats:italic>S. pyogenes<\/jats:italic> and affects 3\u20134% of untreated susceptible children. The immune response against streptococcal antigens can lead cross\u2010recognition of heart tissue proteins resulting in rheumatic heart disease (RHD). HLA class II alleles have been associated with the development of RF\/RHD. Tumor necrosis factor (TNF)\u2010\u03b1 is also located in the same chromosomal region of HLA genes and has been investigated in RHD patients from Mexico, Turkey, and Brazil. Associations with the TNFA\u2010308 allele were found and probably are related to the development of valvular lesions. A deficient mannose\u2010binding lectin (MBL) allele was found in Brazilian patients. MBL is a protein important for the first line of host defense against the bacteria. The association with diverse genes probably indicates a role of certain molecules in both the innate and adaptive immune response. Antigen\u2010presenting cells bearing the HLA\u2010DR7 molecule from RHD patients preferentially recognized a heart\u2010tissue protein cross\u2010reactive M5 (81\u201396) peptide. The same peptide was also recognized by heart tissue T cell clones. Cardiac myosin peptides were recognized by high numbers of intralesional T cell clones. The cytokine pattern of infiltrating mononuclear cells in both myocardium and valvular tissue showed a predominance of proinflammatory cytokines (TNF\u2010\u03b1 and IFN\u2010\u03b3) and scarce production of regulatory cytokines, such as IL\u20104, in the valve tissue. IL\u201010, a predominant regulatory cytokine, was also secreted by large numbers of cells in both valve and myocardium tissue. Data here indicate the complexity of immune reactions leading to autoimmune lesions in RF\/RHD.<\/jats:bold> <\/jats:p>","DOI":"10.1196\/annals.1381.045","type":"journal-article","created":{"date-parts":[[2007,9,5]],"date-time":"2007-09-05T15:32:48Z","timestamp":1189006368000},"page":"426-433","source":"Crossref","is-referenced-by-count":19,"title":["Rheumatic Fever"],"prefix":"10.1111","volume":"1107","author":[{"given":"L.","family":"GUILHERME","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"KALIL","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,8,28]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66874-2"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1601-0825.2002.1o816.x"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1017\/S146239940501015X"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-8411(03)00079-9"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2005.05.005"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2006.10.001"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2006.08.296"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.83.6.1995"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0198-8859(94)90024-8"},{"key":"e_1_2_6_11_2","first-page":"1518","article-title":"Association of HLA\u2010DR7 with rheumatic fever in the Brazilian population","volume":"27","author":"Visentainer J.E.","year":"2000","journal-title":"J. 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