{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:02:09Z","timestamp":1791241329885,"version":"4.1.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The pathogenesis of multiple sclerosis (MS) has not yet been fully uncovered. There is increasing evidence that Epstein-Barr-Virus (EBV) infection, which affects over 90% of people during life and causes infectious mononucleosis, leads to an increased incidence of MS, and thus may play a crucial role in the pathophysiology of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using the Disease Analyzer database (IQVIA) featuring diagnoses as well as basic medical and demographic data of outpatients from general practices in Germany, we identified a total of 16,058 patients with infectious mononucleosis that were matched to a cohort of equal size without infectious mononucleosis based on patients\u2019 age, sex, index year and yearly consultation frequency. Incidence of MS was compared within a 10-year follow-up period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Within 10 years from the index date, the incidence of MS was 22.6 cases per 100,000 person-years among patient with infectious mononucleosis but only 11.9 cases per 100,000 person-years among individuals without infectious mononucleosis. In regression analysis, infectious mononucleosis was significantly associated with the incidence of MS (HR: 1.86, 95% CI: 1.09-3.16). Subgroup analysis revealed the strongest association between infectious mononucleosis and MS in the age group between 14 and 20 years (HR: 3.52, 95% CI: 1.00-12.37) as well as a stronger association in men compared to women.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Infectious mononucleosis is associated with an increased incidence of MS especially in younger individuals. Our data support the growing evidence of a decisive involvement of EBV in the currently unknown pathophysiology of MS and should trigger further research efforts to better understand and potentially prevent cases of this disabling disease in future.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.937583","type":"journal-article","created":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T07:06:50Z","timestamp":1659424010000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Infectious mononucleosis is associated with an increased incidence of multiple sclerosis: Results from a cohort study of 32,116 outpatients in Germany"],"prefix":"10.3389","volume":"13","author":[{"given":"Sven H.","family":"Loosen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Doege","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven G.","family":"Meuth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Luedde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Kostev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Roderburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30443-5","article-title":"Global, regional, and national burden of multiple sclerosis 1990-2016: A systematic analysis for the global burden of disease study 2016","volume":"18","year":"2019","journal-title":"Lancet Neurol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1401483","article-title":"Multiple sclerosis","volume":"378","author":"Reich","year":"2018","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30959-X","article-title":"Diagnosis of multiple sclerosis: Progress and challenges","volume":"389","author":"Brownlee","year":"2017","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1126\/science.abj8222","article-title":"Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis","volume":"375","author":"Bjornevik","year":"2022","journal-title":"Science"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1001\/jama.293.20.2496","article-title":"Temporal relationship between elevation of Epstein-Barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis","volume":"293","author":"Levin","year":"2005","journal-title":"JAMA"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000466","article-title":"Molecular signature of Epstein-Barr virus infection in Ms brain lesions","volume":"5","author":"Moreno","year":"2018","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071030","article-title":"Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain","volume":"204","author":"Serafini","year":"2007","journal-title":"J Exp Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr197","article-title":"Epstein-Barr Virus in the multiple sclerosis brain: A controversial issue\u2013report on a focused workshop held in the centre for brain research of the medical university of Vienna, Austria","volume":"134","author":"Lassmann","year":"2011","journal-title":"Brain"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.5414\/CP203320","article-title":"Basic characteristics and representativeness of the German disease analyzer database","volume":"56","author":"Rathmann","year":"2018","journal-title":"Int J Clin Pharmacol Ther"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e14690","DOI":"10.1111\/ijcp.14690","article-title":"Clinical characteristics and sick leave associated with infectious mononucleosis in a real-world setting in Germany","volume":"75","author":"Kap","year":"2021","journal-title":"Int J Clin Pract"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1177\/20552173211022784","article-title":"Is there an association between multiple sclerosis and osteoarthritis in Germany? 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