AUTHOR=Fevang Børre , Wyller Vegard Bruun Bratholm , Mollnes Tom Eirik , Pedersen Maria , Asprusten Tarjei Tørre , Michelsen Annika , Ueland Thor , Otterdal Kari 

TITLE=Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.715102

DOI=10.3389/fimmu.2021.715102

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><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.</p></sec><sec><title>Methods</title><p>Patients were sampled within 6 weeks of debut of symptoms and after 6 months. Peripheral blood mononuclear cells (PBMC) were cultured and stimulated <italic>in vitro</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, <italic>in vitro</italic> and plasma cohorts, respectively.</p></sec><sec><title>Results</title><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 β-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.</p></sec><sec><title>Conclusion</title><p>Patients developing chronic fatigue after IM have signs of T-cell activation and low-grade chronic inflammation at baseline and after 6 months.</p></sec><sec><title>Clinical Trial Registration</title><p><uri xlink:href="https://clinicaltrials.gov/" xmlns:xlink="http://www.w3.org/1999/xlink">https://clinicaltrials.gov/</uri>, identifier NCT02335437.</p></sec>