{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T02:38:28Z","timestamp":1776998308897,"version":"3.51.4"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2015\u201002419"],"award-info":[{"award-number":["2015\u201002419"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2020\u201001638"],"award-info":[{"award-number":["2020\u201001638"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009778","name":"Region J\u00e4mtland H\u00e4rjedalen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009778","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018367","name":"Swedish Foundation for MS Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018367","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003792","name":"Hj\u00e4rnfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003792","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Several factors have been associated with altered risk of developing multiple sclerosis (MS). Epstein\u2013Barr virus (EBV) is the critical risk factor for MS, but recent studies indicate that human herpesvirus 6A (HHV\u20106A) and cytomegalovirus (CMV) are involved in MS aetiopathogenesis. We recently reported an association between rubella virus (RV) envelope protein 1 (E1) seropositivity and the risk of developing MS. Here, we aimed to further explore this association.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Bio\u2010banked blood samples collected before the onset of MS from 981 cases and 1278 matched controls were analysed for antibodies against RV envelope proteins 1 and 2 (E2), and serum\u2010neurofilament light chain (S\u2010NfL), a marker for axonal injury. The association between RV and MS was analysed with conditional logistic regression, calculating odds ratios (OR) with 95% confidence intervals (CI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Rubella E1 seropositivity was significantly associated with a higher risk of MS development, even when adjusting for EBV, CMV and HHV\u20106A serostatus (OR\u2009=\u20091.67, 95% CI 1.29\u20132.14,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). We also observed an increase in seroreactivity against RV E1 before an increase in S\u2010NfL in MS cases, indicating that increased RV E1 seroreactivity precedes axonal injury in the MS prodrome at group\u2010level. There was no association between RV E2 serostatus and MS risk. The association between RV E1 serostatus and MS risk remained similar when the analysis was restricted to unvaccinated participants (OR\u2009=\u20091.78, 95% CI 1.07\u20132.98,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.028).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results support a broadening of the viral hypothesis in MS, arguing for further studies on the neurotropic RV in MS aetiology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cti2.70094","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T07:41:31Z","timestamp":1776325291000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Seropositivity against rubella virus envelope protein 1, but not 2, is associated with an increased risk of multiple sclerosis"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4261-9434","authenticated-orcid":false,"given":"Jens","family":"Ingvarsson","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences, Neurosciences Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5415-6567","authenticated-orcid":false,"given":"Viktor","family":"Grut","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Neurosciences Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3994-2305","authenticated-orcid":false,"given":"Martin","family":"Bistr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Neurosciences Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linn Persson","family":"Berg","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Institute of Biomedicine University of Gothenburg  Gothenburg Sweden"},{"name":"Department of Clinical Microbiology Sahlgrenska University Hospital  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Butt","sequence":"additional","affiliation":[{"name":"Division of Infections and Cancer Epidemiology German Cancer Research Center  Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgitta","family":"Michels","sequence":"additional","affiliation":[{"name":"Division of Infections and Cancer Epidemiology German Cancer Research Center  Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pernilla","family":"Stridh","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience Karolinska Institutet  Stockholm Sweden"},{"name":"Center for Molecular Medicine Karolinska University Hospital  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomas","family":"Olsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience Karolinska Institutet  Stockholm Sweden"},{"name":"Center for Molecular Medicine Karolinska University Hospital  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Alfredsson","sequence":"additional","affiliation":[{"name":"Institute of Environmental Medicine Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0867-4726","authenticated-orcid":false,"given":"Ingrid","family":"Kockum","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience Karolinska Institutet  Stockholm 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