Format

Send to:

Choose Destination
See comment in PubMed Commons below
PLoS One. 2014 Jan 15;9(1):e85387. doi: 10.1371/journal.pone.0085387. eCollection 2014.

Deficient EBV-specific B- and T-cell response in patients with chronic fatigue syndrome.

Author information

  • 1Institute for Medical Immunology, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany.
  • 2Institute for Medical Immunology, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany ; Julius Wolff Institute, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany.
  • 3Labor Berlin GmbH, Immunology Department, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany.
  • 4Institute for Medical Diagnostics, Berlin, Germany.
  • 5Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Medicine Berlin, Germany ; Department Nephrology, Charité University Medicine Berlin, Germany.
  • 6Institute for Medical Immunology, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany ; Labor Berlin GmbH, Immunology Department, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany.
  • 7Institute for Medical Immunology, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany ; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Medicine Berlin, Germany.

Abstract

Epstein-Barr virus (EBV) has long been discussed as a possible cause or trigger of Chronic Fatigue Syndrome (CFS). In a subset of patients the disease starts with infectious mononucleosis and both enhanced and diminished EBV-specific antibody titers have been reported. In this study, we comprehensively analyzed the EBV-specific memory B- and T-cell response in patients with CFS. While we observed no difference in viral capsid antigen (VCA)-IgG antibodies, EBV nuclear antigen (EBNA)-IgG titers were low or absent in 10% of CFS patients. Remarkably, when analyzing the EBV-specific memory B-cell reservoir in vitro a diminished or absent number of EBNA-1- and VCA-antibody secreting cells was found in up to 76% of patients. Moreover, the ex vivo EBV-induced secretion of TNF-α and IFN-γ was significantly lower in patients. Multicolor flow cytometry revealed that the frequencies of EBNA-1-specific triple TNF-α/IFN-γ/IL-2 producing CD4(+) and CD8(+) T-cell subsets were significantly diminished whereas no difference could be detected for HCMV-specific T-cell responses. When comparing EBV load in blood immune cells, we found more frequently EBER-DNA but not BZLF-1 RNA in CFS patients compared to healthy controls suggesting more frequent latent replication. Taken together, our findings give evidence for a deficient EBV-specific B- and T-cell memory response in CFS patients and suggest an impaired ability to control early steps of EBV reactivation. In addition the diminished EBV response might be suitable to develop diagnostic marker in CFS.

PMID:
24454857
[PubMed - indexed for MEDLINE]
PMCID:
PMC3893202
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk