{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:52:04Z","timestamp":1791301924436,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"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":["Annals of Neurology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Epstein\u2013Barr virus (EBV) has been implicated in the pathogenesis of multiple sclerosis (MS). Elevated immunoglobulin G (IgG) titers against EBV nuclear antigen 1 (EBNA1) represent the most consistent serological marker of MS risk, with levels remaining persistently elevated following disease onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted high\u2010dimensional profiling of virus\u2010specific antibody\u2010associated immune features in 60 individuals with relapsing\u2010onset MS followed over time and in 54 age\u2010 and sex\u2010matched EBV\u2010seropositive healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>EBNA1\u2010specific IgG in MS patients exhibited a distinct proinflammatory Fc signature, characterized by increased affinity for Fc \u03b3 receptors (Fc\u03b3Rs) and enhanced Fc\u2010mediated effector functions, including antibody\u2010dependent phagocytosis, complement activation, and natural killer cell engagement. This signature was not observed for antibodies against other common viral antigens and showed a strong association with MS. Increased Fc\u03b3R binding by IgG, specific for both EBNA1 and the lytic EBV glycoprotein 350 (EBV\u2010gp350) correlated with disease activity, defined as clinical relapse and\/or presence of contrast\u2010enhancing brain lesions (CELs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Both fragment antigen\u2010binding and pro\u2010inflammatory functional Fc\u2010mediated features contribute to the association between EBNA1\u2010specific antibody responses and MS. Fc effector functions of EBV\u2010specific antibodies may actively participate in promoting focal disease activity in MS. ANN NEUROL 2026;100:547\u2013558<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78285","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:17:47Z","timestamp":1781756267000},"page":"547-558","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proinflammatory Epstein\u2013Barr Virus Antibody Functions Track with Disease Activity in Multiple Sclerosis"],"prefix":"10.1002","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6400-8747","authenticated-orcid":false,"given":"Malina","family":"Behrens","sequence":"first","affiliation":[{"name":"Department of Neurology University Hospital M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Terroba\u2010Navajas","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital M\u00fcnster  M\u00fcnster 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