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.
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.
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