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Antibodies against GAS M proteins cross\u2010react with host tissue proteins in the heart and brain leading to the symptomatology observed in ARF\/RHD. As throat carriage of <jats:italic>Streptococcus dysgalactiae<\/jats:italic> subspecies <jats:italic>equisimilis<\/jats:italic> (SDSE) has been reported to be relatively high in some ARF\/RHD endemic regions compared with GAS, and both SDSE and GAS express coiled\u2010coil surface protein called M protein, we hypothesized that streptococci other than GAS can also associated with ARF\/RHD and neurobehavioral abnormalities. Neurobehavioral assessments and electrocardiography were performed on Lewis rats before and after exposure to recombinant GAS and SDSE M proteins. Histological assessments were performed to confirm inflammatory changes in cardiac and neuronal tissues. ELISA and Western blot analysis were performed to determine the cross\u2010reactivity of antibodies with host connective, cardiac and neuronal tissue proteins. Lewis rats injected with M proteins either from GAS or SDSE developed significant cardiac functional and neurobehavioral abnormalities in comparison to control rats injected with phosphate\u2010buffered saline. Antibodies against GAS and SDSE M proteins cross\u2010reacted with cardiac, connective and neuronal proteins. Serum from rats injected with streptococcal antigens showed higher immunoglobulin G binding to the striatum and cortex of the brain. Cardiac and neurobehavioral abnormalities observed in our experimental model were comparable to the cardinal symptoms observed in patients with ARF\/RHD. Here for the first time, we demonstrate in an experimental model that M proteins from different streptococcal species could initiate and drive the autoimmune\u2010mediated cardiac tissue damage and neurobehavioral abnormalities.<\/jats:p>","DOI":"10.1111\/imcb.12571","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T13:38:28Z","timestamp":1657114708000},"page":"653-666","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Characterization of an experimental model to determine streptococcal M protein\u2013induced autoimmune cardiac and neurobehavioral abnormalities"],"prefix":"10.1111","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7190-9666","authenticated-orcid":false,"given":"Rukshan AM","family":"Rafeek","sequence":"first","affiliation":[{"name":"School of Science &amp; Technology University of New England  Armidale NSW 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