{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T09:25:56Z","timestamp":1784280356306,"version":"3.55.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2013,8,6]],"date-time":"2013-08-06T00:00:00Z","timestamp":1375747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Italian Ministry of Health"},{"DOI":"10.13039\/501100004271","name":"Sapienza Universit\u00e0 di Roma","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fondazione Umberto di Mario ONLUS"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,8,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Rheumatic heart disease (RHD) is characterized by the presence of anti-streptococcal group A antibodies and anti-endothelial cell antibodies (AECA). Molecular mimicry between streptococcal antigens and self proteins is a hallmark of the pathogenesis of rheumatic fever. We aimed to identify, in RHD patients, autoantibodies specific to endothelial autoantigens cross-reactive with streptococcal proteins and to evaluate their role in inducing endothelial damage. We used an immunoproteomic approach with endothelial cell-surface membrane proteins in order to identify autoantigens recognized by AECA of 140 RHD patients. Cross-reactivity of purified antibodies with streptococcal proteins was analysed. Homologous peptides recognized by serum cross-reactive antibodies were found through comparing the amino acid sequence of streptococcal antigens with human antigens. To investigate interleukin (IL)-1R-associated kinase (IRAK1) and nuclear factor-\u03baB (NF-\u03baB) activation, we performed a Western blot analysis of whole extracts proteins from unstimulated or stimulated human microvascular cardiac endothelial cells (HMVEC-C). Adhesion molecule expression and release of proinflammatory cytokines and growth factors were studied by multiplex bead based immunoassay kits. We observed anti-vimentin antibodies in sera from 49% RHD AECA-positive patients. Cross-reactivity of purified anti-vimentin antibodies with heat shock protein (HSP)70 and streptopain streptococcal proteins was shown. Comparing the amino acid sequence of streptococcal HSP70 and streptopain with human vimentin, we found two homologous peptides recognized by serum cross-reactive antibodies. These antibodies were able to stimulate HMVEC-C inducing IRAK and NF-\u03baB activation, adhesion molecule expression and release of proinflammatory cytokines and growth factors. In conclusion, streptococcal\u2013vimentin cross-reactive antibodies were able to activate microvascular cardiac endothelium by amplifying the inflammatory response in RHD.<\/jats:p>","DOI":"10.1111\/cei.12135","type":"journal-article","created":{"date-parts":[[2013,5,13]],"date-time":"2013-05-13T10:22:40Z","timestamp":1368440560000},"page":"419-429","source":"Crossref","is-referenced-by-count":26,"title":["Streptococcal\u2013vimentin cross-reactive antibodies induce microvascular cardiac endothelial proinflammatory phenotype in rheumatic heart disease"],"prefix":"10.1093","volume":"173","author":[{"given":"F","family":"Delunardo","sequence":"first","affiliation":[{"name":"Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanit\u00e0, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Scalzi","sequence":"additional","affiliation":[{"name":"Reumatologia, Dipartimento di Medicina Interna e Specialit\u00e0 Mediche, Sapienza Universit\u00e0 di Roma, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Capozzi","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale, Sapienza Universit\u00e0 di Roma, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Camerini","sequence":"additional","affiliation":[{"name":"Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanit\u00e0, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Misasi","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale, Sapienza Universit\u00e0 di Roma, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Pierdominici","sequence":"additional","affiliation":[{"name":"Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanit\u00e0, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Pendolino","sequence":"additional","affiliation":[{"name":"Reumatologia, Dipartimento di Medicina Interna e Specialit\u00e0 Mediche, Sapienza Universit\u00e0 di Roma, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Crescenzi","sequence":"additional","affiliation":[{"name":"Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanit\u00e0, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Sorice","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale, Sapienza Universit\u00e0 di Roma, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Valesini","sequence":"additional","affiliation":[{"name":"Reumatologia, Dipartimento di Medicina Interna e Specialit\u00e0 Mediche, Sapienza Universit\u00e0 di Roma, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Ortona","sequence":"additional","affiliation":[{"name":"Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanit\u00e0, Roma, Italy"},{"name":"Istituto San Raffaele Sulmona, Sulmona (AQ), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Alessandri","sequence":"additional","affiliation":[{"name":"Reumatologia, Dipartimento di Medicina Interna e Specialit\u00e0 Mediche, Sapienza Universit\u00e0 di Roma, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,8,6]]},"reference":[{"key":"2021122009565605500_cei12135-bib-0001","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1001\/jama.1992.03490150121036","article-title":"Guidelines for the diagnosis of rheumatic fever. 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