{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:51:10Z","timestamp":1790682670125,"version":"4.1.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"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>Epstein-Barr virus (EBV) causes infectious mononucleosis (IM) that can lead to chronic fatigue syndrome. The CEBA-project (Chronic fatigue following acute EBV infection in Adolescents) has followed 200 patients with IM and here we present an immunological profiling of adolescents with IM related to clinical characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients were sampled within 6 weeks of debut of symptoms and after 6 months. Peripheral blood mononuclear cells (PBMC) were cultured and stimulated <jats:italic>in vitro<\/jats:italic> (n=68), and supernatants analyzed for cytokine release. Plasma was analyzed for inflammatory markers (n=200). The Chalder Fatigue Questionnaire diagnosed patients with and without chronic fatigue at 6 months (CF+ and CF- group, respectively) (n=32 and n=91, <jats:italic>in vitro<\/jats:italic> and plasma cohorts, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Broad activation of PBMC at baseline, with high levels of RANTES (Regulated on activation, normal T-cell expressed and secreted) in the CF+ group, and broad inflammatory response in plasma with high levels of T-cell markers was obeserved. At 6 months, there was an increased \u03b2-agonist response and RANTES was still elevated in cultures from the CF+ group. Plasma showed decrease of inflammatory markers except for CRP which was consistently elevated in the CF+ group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients developing chronic fatigue after IM have signs of T-cell activation and low-grade chronic inflammation at baseline and after 6 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration<\/jats:title><jats:p><jats:uri>https:\/\/clinicaltrials.gov\/<\/jats:uri>, identifier NCT02335437.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.715102","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T08:04:10Z","timestamp":1639987450000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and 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