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

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.