{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:25:41Z","timestamp":1791278741231,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,3,13]],"date-time":"2013-03-13T00:00:00Z","timestamp":1363132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Current or recent enteroviral infections show an association with type 1 diabetes. However, evidence for this has mainly been generated using a particular mouse monoclonal antibody (clone 5\u2010<jats:styled-content style=\"fixed-case\">D8<\/jats:styled-content>\/1) which binds the viral capsid protein <jats:styled-content style=\"fixed-case\">VP1<\/jats:styled-content>. Difficulty in confirming these findings using other independent methods has led to the concern that this might be artefactual. To address this, we examined the potential cross\u2010reactivity of clone 5\u2010<jats:styled-content style=\"fixed-case\">D8<\/jats:styled-content>\/1 with normal islet proteins. Western blotting, two\u2010dimensional gel electrophoresis, and mass spectrometry were used to identify human islet proteins bound by the clone 5\u2010<jats:styled-content style=\"fixed-case\">D8<\/jats:styled-content>\/1. We found a distinct reactivity with two mitochondrial proteins, creatine kinase B\u2010type and <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> synthase beta subunit. Immunohistochemistry using the clone 5\u2010<jats:styled-content style=\"fixed-case\">D8<\/jats:styled-content>\/1 revealed a granular cytoplasmic staining pattern in mitochondria\u2010rich cells, ie hepatocytes, ductal epithelial cells, vascular endothelial cells, skeletal muscle cells, and the neoplastic salivary gland oncocytoma cells, whereas connective tissue and infiltrating immune cells were negative. Staining on islets of Langerhans from subjects with recent\u2010onset type 1 diabetes, but not on isolated human islets infected <jats:italic>in vitro<\/jats:italic> with enteroviruses, could be blocked after mixing the clone 5\u2010<jats:styled-content style=\"fixed-case\">D8<\/jats:styled-content>\/1 with the mitochondrial proteins. Collectively, our data show that the clone 5\u2010<jats:styled-content style=\"fixed-case\">D8<\/jats:styled-content>\/1 detects two human mitochondrial enzymes in addition to enteroviral <jats:styled-content style=\"fixed-case\">VP1<\/jats:styled-content>. The notion that the previously reported <jats:styled-content style=\"fixed-case\">VP1<\/jats:styled-content> positivity in islets of recent\u2010onset type 1 diabetes patients could reflect cross\u2010reactivity to native islet proteins and not the presence of <jats:styled-content style=\"fixed-case\">EV<\/jats:styled-content> is supported by difficulties in demonstrating <jats:styled-content style=\"fixed-case\">EV<\/jats:styled-content> infection by independent techniques such as <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> or <jats:italic>in situ<\/jats:italic> hybridization. These findings call for revisiting the presence of enteroviruses in pancreatic islets of patients with type 1 diabetes. Copyright \u00a9 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:bold><\/jats:p>","DOI":"10.1002\/path.4166","type":"journal-article","created":{"date-parts":[[2013,1,17]],"date-time":"2013-01-17T13:38:59Z","timestamp":1358429939000},"page":"719-728","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Enteroviruses and the pathogenesis of type 1 diabetes revisited: cross\u2010reactivity of enterovirus capsid protein (<scp>VP1<\/scp>) antibodies with human mitochondrial proteins"],"prefix":"10.1002","volume":"229","author":[{"given":"Sara F","family":"Hansson","sequence":"first","affiliation":[{"name":"Proteomics Core Facility University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Korsgren","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology Uppsala University  Uppsala 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