{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:51:32Z","timestamp":1791204692546,"version":"4.2.0"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Epstein\u2013Barr Virus (EBV) and its clinical manifestation, infectious mononucleosis (IM), are strongly linked to MS risk. A recent in\u00a0vitro study suggests that\n HLA\u2010E*01:03<\/jats:italic>\n , in contrast to\n HLA\u2010E*01:01<\/jats:italic>\n , may protect against MS through more effective immune responses against EBV\u2010infected B cells. However, the role of\n HLA\u2010E*01<\/jats:italic>\n in MS remains unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We investigated if\n HLA\u2010E*01:01<\/jats:italic>\n was significantly associated with higher MS risk in individuals with a history of IM diagnosis, using 487,144 individuals from the UK Biobank's cohort. We estimated the interaction between\n HLA\u2010E*01:01<\/jats:italic>\n and IM using Cox proportional hazard models, adjusting for demographics, smoking, childhood body size, older siblings, and MS\u2010related HLA alleles (e.g.,\n HLA\u2010DRB1*15:01<\/jats:italic>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n HLA\u2010E*01:01<\/jats:italic>\n allele alone was not significantly associated with IM or MS (\n p<\/jats:italic>\n \u2009>\u20090.05). However, a significant interaction between\n HLA\u2010E*01:01<\/jats:italic>\n and IM history was observed in relation to MS risk (\n p<\/jats:italic>\n \u2009<\u20090.001). Specifically, MS risk was significantly higher in both\n HLA\u2010E*01:01<\/jats:italic>\n heterozygotes (HR\u2009=\u20091.74 [95% CI: 1.36, 1.97],\n p<\/jats:italic>\n \u2009<\u20090.001) and homozygotes (HR\u2009=\u20093.01 [95% CI: 1.81, 3.88],\n p<\/jats:italic>\n \u2009<\u20090.001) with IM history, compared to\n HLA\u2010E*01:03<\/jats:italic>\n homozygotes\n .<\/jats:italic>\n Conversely, these associations were non\u2010significant in individuals without IM history (\n p<\/jats:italic>\n \u2009>\u20090.05). The estimated proportion of the combined risk attributable to interaction effects was 40% in\n HLA\u2010E*01:01<\/jats:italic>\n heterozygotes and 65% in\n HLA\u2010E*01:01<\/jats:italic>\n homozygotes.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n HLA\u2010E*01:01<\/jats:italic>\n carriers diagnosed with IM are at significantly increased risk of MS, independently from other MS\u2010related HLA alleles. This supports the hypothesis that\n HLA\u2010E*01:01<\/jats:italic>\n may contribute to MS susceptibility due to weaker immune control over EBV infection. Incorporating\n HLA\u2010E*01:01<\/jats:italic>\n into existing MHC\u2010based MS risk models could then enhance personalized risk assessments in individuals with IM history.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/ene.70131","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T12:27:20Z","timestamp":1744028840000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Stratifying Multiple Sclerosis Susceptibility Risk: The Role of\n HLA\u2010E*01<\/i>\n and Infectious Mononucleosis in a Population Cohort"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7258-1938","authenticated-orcid":false,"given":"Andrea","family":"Nova","sequence":"first","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8391-0725","authenticated-orcid":false,"given":"Davide","family":"Gentilini","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia Pavia Italy"},{"name":"Bioinformatics and Statistical Genomic Unit IRCCS Istituto Auxologico Italiano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1913-9897","authenticated-orcid":false,"given":"Giovanni","family":"Di Caprio","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2452-2861","authenticated-orcid":false,"given":"Sonia","family":"Bourguiba\u2010Hachemi","sequence":"additional","affiliation":[{"name":"Center for Research in Transplantation and Translational Immunology, UMR 1064 Nantes Universit\u00e9, CHU Nantes, INSERM Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3767-6210","authenticated-orcid":false,"given":"Nicolas","family":"Vince","sequence":"additional","affiliation":[{"name":"Center for Research in Transplantation and Translational Immunology, UMR 1064 Nantes Universit\u00e9, CHU Nantes, INSERM Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4176-8388","authenticated-orcid":false,"given":"Pierre\u2010Antoine","family":"Gourraud","sequence":"additional","affiliation":[{"name":"Center for Research in Transplantation and Translational Immunology, UMR 1064 Nantes Universit\u00e9, CHU Nantes, INSERM Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7551-6664","authenticated-orcid":false,"given":"Luisa","family":"Bernardinelli","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9577-8450","authenticated-orcid":false,"given":"Teresa","family":"Fazia","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.17879\/freeneuropathology\u20102023\u20104675"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58649"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.16088"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj8222"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.11.015"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.11.023"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adg3032"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012496"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.937583"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2011.42"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.01368"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000203"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20215496"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2022.04.010"},{"key":"e_1_2_9_16_1","article-title":"Multiple Sclerosis Genomic Map Implicates Peripheral Immune Cells and Microglia in Susceptibility","volume":"365","author":"Patsopoulos N. 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