No association found between the detection of either xenotropic murine leukemia virus-related virus or polytropic murine leukemia virus and chronic fatigue syndrome in a blinded, multi-site, prospective study by the establishment and use of the SolveCFS BioBank

Abstract

BackgroundIn 2009, a retrospective study reported the detection of xenotropic murine leukemia virus-related virus (XMRV) in clinical isolates derived from individuals with chronic fatigue syndrome or myalgic encephalomyelitis (CFS). While many efforts to confirm this observation failed, one report detected polytropic murine leukemia virus (pMLV), instead of XMRV. In both studies, Polymerase Chain Reaction (PCR)-based methods were employed which could provide the basis for the development of a practical diagnostic tool. To confirm these studies, we hypothesized that the ability to detect these viruses will not only depend upon the technical details of the methods employed but also on the criteria used to diagnose CFS and the availability of well characterized clinical isolates.MethodsA repository of clinical isolates from geographically distinct sites was generated by the collection of fresh blood samples from well characterized CFS and healthy subjects. Molecular techniques were used to generate assay positive controls and to determine the lower limit of detection (LLOD) for murine retroviral and Intracisternal A particle (Cell 12(4):963-72, 1977) detection methods.ResultsWe report the establishment of a repository of well-defined, clinical isolates from five, geographically distinct regions of the US, the comparative determination of the LLODs and validation efforts for the previously reported detection methods and the results of an effort to confirm the association of these retroviral signatures in isolates from individuals with CFS in a blinded, multi-site, prospective study. We detected various, murine retroviral DNA signatures but were unable to resolve a difference in the incidence of their detection between isolates from CFS (5/72; 6.7%) and healthy (2/37; 5.4%) subjects (Fisher’s Exact Test, p-value = 1). The observed sequences appeared to reflect the detection of endogenous murine retroviral DNA, which was not identical to either XMRV or pMLV.ConclusionsWe were unable to confirm a previously reported association between the detection of XMRV or pMLV sequences and CFS in a prospective, multi-site study. Murine retroviral sequences were detected at a low frequency that did not differ between CFS and control subjects. The nature of these sequences appeared to reflect the detection of pre-existing, endogenous, murine retroviral DNA in the PCR reagents employed.

The utility of patient-reported outcome measures among patients with myalgic encephalomyelitis/chronic fatigue syndrome

“…The original study was designed to evaluate the role that methodological approaches had in the previously identified, and now largely rejected, association between xenotropic murine leukemia virus and ME/CFS [32]. The data was collected between June and August 2010.…”

“…Participants with ME/CFS also had to have post-exertional malaise lasting >24 hours and significant cognitive impairment in short-term memory and concentration. The final sample included 240 ME/CFS patients who were recruited from four clinical sites as previously report by Irbeck et al [32]. A total of 88 healthy individuals were recruited for the control group, who were matched to ME/CFS patients by zip code (excluded if they lived within the same household), age, sex, and race.…”

Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

“…It has been suggested that the earlier positive findings were based on laboratory contamination [ 136 – 140 ]. Studies have shown that commercial reagents and clinical samples could be contaminated with MLV-related virus genomic sequences containing murine DNA, and cloned or amplified XMRV DNA might be the source of contamination.…”

Markers of non-coeliac wheat sensitivity in patients with myalgic encephalomyelitis/chronic fatigue syndrome

“…We considered whether a subset of patients with ME/CFS may exhibit serologic markers associated with NCWS, which might explain some of the corresponding symptoms. We screened serum samples from 131 patients with ME/CFS and 86 healthy controls (table 1), recruited as previously described,9 for the same markers as those in the above-mentioned study on NCWS 1. Questionnaires were used to assess GI symptoms within the past 6 months, including abdominal pain, bloating and nausea.…”