Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach

Abstract

Aims: The aetiology for chronic fatigue syndrome remains elusive although enteroviruses have been implicated as one of the causes by a number of studies. Since most CFS patients have persistent or intermittent gastrointestinal (GI) symptoms, we evaluated the presence of viral capsid protein 1(VP1), Enterovirus RNA and culturable virus in the stomach biopsies of CFS patients. Methods: 165 consecutive CFS patients underwent upper GI endoscopies and antrum biopsies. Immunoperoxidase staining was performed using enterovirus-specific monoclonal antibody (mAb) or a control mAb specific for cytomegalovirus. RT-PCR ELISA was performed on RNA extracted from paraffin sections or samples preserved in RNA-later. Biopsies from normal stomach and other gastric diseases served as controls. 75 samples were cultured for enterovirus. Results: 135/165 (82%) biopsies stained positive for VP1 within parietal cells, whereas 7/34 (20%) of the controls stained positive (P <0.000001). CMV mAb failed to stain any of the biopsy specimens. Biopsies taken from 6 patients at the onset of the CFS/abdominal symptoms, and 2-8 years later demonstrated positive staining in the paired specimens. EV RNA was detected in 9/24 (37 %) paraffin-embedded biopsy samples, and 1/21 controls had detectable EV RNA (p<0.01). 1/3 patient had detectable EV RNA from two samples taken 4 years apart. 5 patient samples demonstrated transient growth of non-cytopathic enteroviruses. Conclusion: Enterovirus VP1, RNA and non-cytopathic viruses were detected in the stomach biopsies of CFS patients with chronic abdominal complaints. A significant subset of CFS patients may have chronic, disseminated, non-cytolytic form of enteroviral infection, which could be diagnosed by stomach biopsies.