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

Front Immunol. 2021 Dec 20:12:715102. doi: 10.3389/fimmu.2021.715102. eCollection 2021.

Abstract

Background: 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.

Methods: Patients were sampled within 6 weeks of debut of symptoms and after 6 months. Peripheral blood mononuclear cells (PBMC) were cultured and stimulated in vitro (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, in vitro and plasma cohorts, respectively.

Results: 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.

Conclusion: Patients developing chronic fatigue after IM have signs of T-cell activation and low-grade chronic inflammation at baseline and after 6 months.

Clinical trial registration: https://clinicaltrials.gov/, identifier NCT02335437.

Keywords: CFS; CRP; EBV; Epstein-Barr virus; RANTES; chronic fatigue syndrome; fatigue; infectious mononucleosis.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Viral / blood
  • Biomarkers
  • Cells, Cultured
  • Chemokine CCL5 / biosynthesis
  • Chemokine CCL5 / blood*
  • Chronic Disease
  • Convalescence
  • Cross-Sectional Studies
  • Cytokines / blood
  • Fatigue Syndrome, Chronic / blood
  • Fatigue Syndrome, Chronic / etiology*
  • Fatigue Syndrome, Chronic / immunology
  • Female
  • Follow-Up Studies
  • Herpesvirus 4, Human / immunology
  • Humans
  • Infectious Mononucleosis / blood
  • Infectious Mononucleosis / complications
  • Infectious Mononucleosis / immunology*
  • Inflammation / blood
  • Inflammation / etiology*
  • Inflammation / immunology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation*
  • Male
  • Prospective Studies
  • Receptors, Adrenergic, beta / physiology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Antibodies, Viral
  • Biomarkers
  • CCL5 protein, human
  • Chemokine CCL5
  • Cytokines
  • Receptors, Adrenergic, beta

Associated data

  • ClinicalTrials.gov/NCT02335437