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Myalgic encephalomyelitis (ME) is a debilitating illness of unknown etiology characterized by neurocognitive dysfunction, inflammation, immune abnormalities and gastrointestinal distress. An increasing body of evidence suggests that disruptions in the gut may contribute to the induction of neuroinflammation. Therefore, reports of human endogenous retroviral (HERV) expression in association with neuroinflammatory diseases prompted us to investigate the gut of individuals with ME for the presence of HERV proteins. In eight out of 12 individuals with ME, immunoreactivity to HERV proteins was observed in duodenal biopsies. In contrast, no immunoreactivity was detected in any of the eight controls. Immunoreactivity to HERV Gag and Env proteins was uniquely co-localized in hematopoietic cells expressing the C-type lectin receptor CLEC4C (CD303/BDCA2), the co-stimulatory marker CD86 and the class II major histocompatibility complex HLA-DR, consistent with plasmacytoid dendritic cells (pDCs). Although the significance of HERVs present in the pDCs of individuals with ME has yet to be determined, these data raise the possibility of an involvment of pDCs and HERVs in ME pathology. To our knowledge, this report describes the first direct association between pDCs and HERVs in human disease.

Background: Human herpesvirus-6 (HHV-6), Epstein-Barr virus and parvovirus B19 have been suggested as etiological agents of chronic fatigue syndrome but none of these viruses is consistently detected in all patients. However, active viral infections may be localized in specific tissues, and, therefore, are not easily detectable. The aim of this study was to investigate the presence of HHV-6, HHV-7, EBV and parvovirus B19 in the gastro-intestinal tract of CFS patients., Patients and Methods: Using real-time PCR, viral DNA loads were quantified in gastro-intestinal biopsies of 48 CFS patients and 35 controls., Results: High loads of HHV-7 DNA were detected in most CFS and control biopsies. EBV and HHV-6 were detected in 15-30% of all biopsies. Parvovirus B19 DNA was detected in 40% of the patients versus less than 15% of the controls., Conclusion: Parvovirus B19 may be involved in the pathogenesis of CFS, at least for a subset of patients. The gastro-intestinal tract appears as an important reservoir of infection for several potentially pathogenic viruses.

This study examined possible interactions between immunological abnormalities and symptoms in CFS. Sixteen CFS patients filled in a battery of questionnaires, evaluating daily functioning, and underwent venous blood sampling, in order to analyse immunological abnormalities. Ribonuclease (RNase) L cleavage was associated with RNase L activity (rs=0.570; p=0.021), protein kinase R (PKR) (rs=0.716; p=0.002) and elastase activity (rs=0.500; p=0.049). RNase L activity was related to elastase (rs=0.547; p=0.028) and PKR activity (rs=0.625; p=0.010). RNase L activity (rs=0.535; p=0.033), elastase activity (rs=0.585; p=0.017) and RNase L cleavage (rs=0.521; p=0.038) correlated with daily functioning. This study suggests that in CFS patients an increase in elastase activity and subsequent RNase L cleavage is accompanied by increased activity of both the PKR and RNase L enzymes. RNase L and elastase activity are related to daily functioning, thus evidence supporting the clinical importance of these immune dysfunctions in CFS patients was provided.