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This was a prospective and observational study including patients with RRMS with active and inactive disease and healthy controls. Blood EVs were isolated by precipitation. Titers of antibodies against nuclear (anti-EBNA1) and capsid (anti-VCA) EBV antigens in EVs and in plasma, as well as content of myelin antibodies in EVs were determined by ELISA. An exploratory analysis of correlations with clinical and radiological data was performed. Patients with RRMS had higher titers of anti-VCA inside EVs and free in plasma than healthy controls. Patients with active disease showed higher levels of anti-EBNA1 in EVs, but not in plasma, than patients with inactive disease. EV anti-VCA levels correlated with disease duration and with decreased brain volume structures\u2014total brain, white matter, gray matter, cerebellum, hippocampus, \u2014but not with T2\/FLAIR lesion volume or EDSS, SDMT, or 9HPT. In addition, EV anti-VCA correlated with EV anti-MBP. The anti-VCA and anti-EBNA1 content in EVs could represent diagnostic and disease activity blood biomarkers, respectively, in RRMS.<\/jats:p>","DOI":"10.3390\/ijms241814192","type":"journal-article","created":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T06:36:45Z","timestamp":1694932605000},"page":"14192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Antibody Content against Epstein\u2013Barr Virus in Blood Extracellular Vesicles Correlates with Disease Activity and Brain Volume in Patients with Relapsing\u2013Remitting Multiple Sclerosis"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4885-0181","authenticated-orcid":false,"given":"Mireya","family":"Fern\u00e1ndez-Fournier","sequence":"first","affiliation":[{"name":"Neuroimmunology and Multiple Sclerosis Unit, Department of Neurology, Neurological Sciences and Cerebrovascular Research Laboratory, Neurology and Cerebrovascular Disease Group, Neuroscience Area of Hospital La Paz Institute for Health Research\u2014IdiPAZ (La Paz University Hospital\u2014Universidad Aut\u00f3noma de Madrid), 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MariPaz","family":"L\u00f3pez-Molina","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Multiple Sclerosis Unit, Department of Neurology, Neurological Sciences and Cerebrovascular Research Laboratory, Neurology and Cerebrovascular Disease Group, Neuroscience Area of Hospital La Paz Institute for Health Research\u2014IdiPAZ (La Paz University Hospital\u2014Universidad Aut\u00f3noma de Madrid), 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Torres Iglesias","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Multiple Sclerosis Unit, Department of Neurology, Neurological Sciences and Cerebrovascular Research Laboratory, Neurology and 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