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

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.

Source: Fevang B, Wyller VBB, Mollnes TE, Pedersen M, Asprusten TT, Michelsen A, Ueland T, Otterdal K. 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. PMID: 34987499; PMCID: PMC8721200. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721200/ (Full text)

Viral infection and its causative role for chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS), of unknown etiology, have been increasingly reported. This syndrome is characterized by debilitating fatigue, lymphadenopathy, and fever. Herein, I focus on and review this syndrome from the view point of the causative role of viral infection. Since the symptoms of CFS are similar to those of chronic infectious mononucleosis (CIM) or chronic Epstein-Barr virus infection (CEBV), the role of EBV has been intensively studied. The etiological relationship between EBV and CFS, however, is questioned, like other lymphotropic viruses, including human retroviruses, adenoviruses and human herpesvirus 6. Additionally, severe chronic active EBV infection syndrome (SCAEBV) is also discussed in this review because symptoms of this disorder are similar to those of CFS but more severe in degree. Currently, the cause(s) and treatment of CFS are enigmatic and require further research and multidisciplinary study.

 

Source: Okano M. Viral infection and its causative role for chronic fatigue syndrome. Nihon Rinsho. 1992 Nov;50(11):2617-24. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337559