{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:59:47Z","timestamp":1780574387836,"version":"3.54.1"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T00:00:00Z","timestamp":1647043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Multiple sclerosis (MS) is characterized by inflammatory lesions in the central nervous system involving pro-inflammatory T-cells. Immune dysregulation is well described in prevalent disease, but it is not known whether this precedes disease development. Bacillus Calmette\u2013Gu\u00e9rin (BCG) vaccination ameliorates MS-like disease in mice. In people vaccinated with BCG, the tuberculin skin test (TST) offers a standardized measure of a T-cell-mediated immune response. We therefore hypothesized that the strength of the TST response after BCG vaccination is associated with subsequent MS risk.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Using data from a Norwegian tuberculosis screening programme (1963\u20131975), we designed a population-based cohort study and related the size of TST reactions in individuals previously vaccinated with BCG to later MS disease identified through the Norwegian MS registry. We fitted Cox proportional hazard models and flexible parametric survival models to investigate the association between TST reactivity, MS risk and its temporal relationship.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among 279\u200a891 participants (52% females), 679 (69% females) later developed MS. Larger TST reactivity was associated with decreased MS risk. The hazard ratio for MS per every 4-mm increase in skin induration size was 0.86 (95% confidence interval 0.76\u20130.96) and similar between sexes. The strength of the association persisted for &amp;gt;30\u2009years after the TST.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>A strong in vivo vaccine response to BCG is associated with reduced MS risk &amp;gt;30 years later. The immunological mechanisms determining TST reactivity suggest that skewed T-cell-mediated immunity precedes MS onset by many decades.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ije\/dyac039","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T12:11:34Z","timestamp":1645186294000},"page":"1637-1644","source":"Crossref","is-referenced-by-count":8,"title":["Strong tuberculin response after BCG vaccination is associated with low multiple sclerosis risk: a population-based cohort study"],"prefix":"10.1093","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4765-0636","authenticated-orcid":false,"given":"Ola","family":"Nakken","sequence":"first","affiliation":[{"name":"Department of Neurology, Akershus University Hospital , L\u00f8renskog, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trygve","family":"Holm\u00f8y","sequence":"additional","affiliation":[{"name":"Department of Neurology, Akershus University Hospital , L\u00f8renskog, Norway"},{"name":"Institute of Clinical Medicine, University of Oslo , Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hein","family":"Stigum","sequence":"additional","affiliation":[{"name":"Department of Physical Health and Ageing, Norwegian Institute of Public Health , Oslo, Norway"},{"name":"Department of Community Medicine and Global Health, University of Oslo , Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjell-Morten","family":"Myhr","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, University of Bergen , Bergen, Norway"},{"name":"Neuro-SysMed, Department of Neurology, Haukeland University Hospital , Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"Dahl","sequence":"additional","affiliation":[{"name":"Department of Physical Health and Ageing, Norwegian Institute of Public Health , Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Einar","family":"Heldal","sequence":"additional","affiliation":[{"name":"Department of Physical Health and Ageing, Norwegian Institute of Public Health , Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haakon E","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Physical Health and Ageing, Norwegian Institute of Public Health , Oslo, Norway"},{"name":"Department of Community Medicine and Global Health, University of Oslo , Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,12]]},"reference":[{"key":"2022101416064061400_dyac039-B1","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1177\/1352458520970841","article-title":"Rising prevalence of multiple sclerosis worldwide: insights from the Atlas of MS","volume":"26","author":"Walton","year":"2020","journal-title":"Mult Scler"},{"key":"2022101416064061400_dyac039-B2","doi-asserted-by":"crossref","first-page":"17562864211007687","DOI":"10.1177\/17562864211007687","article-title":"Inflammation in multiple sclerosis","volume":"14","author":"Haase","year":"2021","journal-title":"Ther Adv Neurol Disord"},{"key":"2022101416064061400_dyac039-B3","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nature10251","article-title":"Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis","volume":"476","author":"Sawcer","year":"2011","journal-title":"Nature"},{"key":"2022101416064061400_dyac039-B4","doi-asserted-by":"crossref","first-page":"248ra107","DOI":"10.1126\/scitranslmed.3008879","article-title":"B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes","volume":"6","author":"Stern","year":"2014","journal-title":"Sci Transl Med"},{"key":"2022101416064061400_dyac039-B5","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/ana.21117","article-title":"Environmental risk factors for multiple sclerosis. 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