{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T01:08:09Z","timestamp":1793495289505,"version":"4.5.0"},"reference-count":125,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":41,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIAID; ACS; NIDCR","award":["UM1AI109565,PF-21-084-01-DMC,T32AI052077,R01DE025994"],"award-info":[{"award-number":["UM1AI109565,PF-21-084-01-DMC,T32AI052077,R01DE025994"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,23]]},"abstract":"<jats:p>\n                    Epstein-Barr virus (EBV) infection precedes multiple sclerosis (MS) onset and plays a poorly understood etiologic role. To investigate possible viral pathogenesis, we analyzed single-cell expression in peripheral B cells from people with early MS collected longitudinally during the Immune Tolerance Network STAyCIS Trial. Expression profiles were compared with single-cell RNA-Seq (scRNA-Seq) from in vitro EBV models, autoimmune disorders, chronic infectious diseases, and healthy controls. Analyses focused on CD19\n                    <jats:sup>+<\/jats:sup>\n                    CD20\n                    <jats:sup>+<\/jats:sup>\n                    CD21\n                    <jats:sup>lo<\/jats:sup>\n                    CD11c\n                    <jats:sup>+<\/jats:sup>\n                    T-bet\n                    <jats:sup>+<\/jats:sup>\n                    atypical B cells (ABCs). ABCs were significantly enriched in early MS PBMCs versus healthy controls by scRNA-Seq and flow cytometry, establishing ABC expansion as a clinical feature. EBV-associated ABC expression, including CXCR3, programmed cell death ligand 1 (PD-L1), and PD-L2, was enriched in early MS; however, direct EBV infection of ABCs was not detected. Early MS ABCs exhibited significantly upregulated inflammatory cytokine mRNAs (\n                    <jats:italic>CXCL8<\/jats:italic>\n                    ,\n                    <jats:italic>IL18<\/jats:italic>\n                    ,\n                    <jats:italic>VEGFA<\/jats:italic>\n                    ). Further, de novo EBV-infected B cells secreted IL-8 and VEGF. MS activity stratification revealed rare, distinctive inflammatory ABCs significantly underrepresented in individuals with no evidence of activity long-term versus people with additional relapsing-remitting MS activity at the primary endpoint. Moreover, CXCR3\n                    <jats:sup>+<\/jats:sup>\n                    ABCs increased after baseline diagnosis and were significantly enriched in people with disease exacerbation during the study. Thus, ABC expansion and inflammatory responses correlate to early MS activity, possibly as a bystander response to EBV.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.188543","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T12:00:20Z","timestamp":1747137620000},"source":"Crossref","is-referenced-by-count":23,"title":["Early multiple sclerosis activity associated with TBX21+CD21loCXCR3+ B cell expansion resembling EBV-induced phenotypes"],"prefix":"10.1172","volume":"10","author":[{"given":"Elliott D.","family":"SoRelle","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellora","family":"Haukenfrers","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian Q.","family":"Horn","sequence":"additional","affiliation":[{"name":"Department of Integrative Immunobiology, Duke University School of Medicine, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8505-9778","authenticated-orcid":true,"given":"Vaibhav","family":"Jain","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Giarraputo","sequence":"additional","affiliation":[{"name":"Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Abramson","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Hocke","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Cooney","sequence":"additional","affiliation":[{"name":"Immune Tolerance Network, Bethesda, Maryland, USA."},{"name":"Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6957-514X","authenticated-orcid":true,"given":"Kristina M.","family":"Harris","sequence":"additional","affiliation":[{"name":"Immune Tolerance Network, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2720-9915","authenticated-orcid":true,"given":"Scott 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