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.
Figure 2 and its legend should appear as follows: Figure 2. Spatial distribution of characteristic m/z values for the traumatized, trauma adjacent, and healthy muscle regions. (A) Average peak MALDI mass spectra intensity of primary trauma (tm, red) and trauma adjacent muscle/healthy (hm, tam, blue) region. (B) HE staining of the healthy and the injured soleus muscle in the region of interest are indicated by the red (tm), black (tam), and green (hm) frame. Ion density distributions to the corresponding spectra peak intensity by using (C) supervised approach (ClinProTools) and (D) unsupervised approach (SCiLS Lab). The m/z values 976 and 1488 show significantly lower intensities (p < 0.05) in the primary trauma region (tm) compared to the trauma adjacent (tam) or healthy (hm) muscle regions. In contrast, the m/z values 985 and 1255 exhibited significantly higher intensities (p < 0.05) in the primary trauma region (tm) compared to tam and hm regions. C
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