Journal reference: Lo S-C, Pripuzova N, Li B, et al. Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors. PNAS September 7, 2010 vol. 107 no. 36 15874-15879 ^[1]

Link: http://dx.doi.org/10.1073/pnas.1006901107

Evidence cookie says...

There appears to be an association between chronic fatigue syndrome (CFS) and murine leukaemia virus (MLV)-related virus. This is the second study to report an association and research is still in early stages.  The role of these viruses in aetiology should not be assumed. Basic science: no direct change in the clinical management of chronic fatigue syndrome is indicated.

More details:

Article details

Study design:

Study aim:

to detect MLV gene sequences in blood of CFS patients

Methods summary:

• Frozen serum and whole blood samples from 37 CFS patients collected in the mid-1990s
• Repeat testing of blood 2 years later of four patients; 8 patients re-tested 15 years later
• 44 blood donor healthy controls
• Molecular assay targeting MLV specific gene and confirmation by gene sequencing

Results summary:

• 32 of 37 (86.5%) of CFS patients were positive for PCR products of MLV
• Repeat testing of samples obtained 2-15 years later was positive in 11 patients (out of 12 tested)
• 3 of 44 (6.8%) healthy controls had a positive PCR product in peripheral blood mononuclear cells
• Phylogenetic analysis showed significant variation in gene sequences of positive patients
• Samples were tested for the presence of mouse DNA to exclude contamination as a cause for positive result → no mouse DNA was found.

Study conclusion:

86.5% of CFS patients tested positive for gene products of MLV compared to only 6.8% of healthy controls. While no aetiological role is established, this may have implications for blood donor testing and pathogenic potential of this retrovirus.

Participants:

• 25 of the CFS patients were from an academic medical centre:
  • none were related
  • and all met the 1988 CDC criteria for CFS
  • average age was 44.4
  • the majority (21 of 25) were female
• 44 normal blood donors samples were collected from 2003- 2006

Methodological weaknesses

• Retrospective nature of the study and small sample size limits the conclusions that can be made.
• Mixed collection and storage methods of blood, with some frozen and 2010 samples processed without being frozen.
• Importantly, the blood samples for the controls and the CFS patients have been sourced as groups very differently; this is an introduction of a serious source of potential bias:
  • CFS patient samples: 29 or 41 patient samples were collected by one researcher at the Chronic Fatigue Research Centre, Brigham and Women’s Hospital (Boston, MA)
  • Controls: 44 normal blood donors from the Washington, DC, area were collected in 2003-2006 and stored at the Department of Transfusion Medicine, Clinical Centre, National Institute of Health
• The diagnosis of CFS was based on 1988 CDC criteria.
• The article does not provide any clinical data on the normal blood donor samples such as age, sex or clinical follow up for development of CFS.
• Any PCR based study is subject to false positives from contamination
• Does not provide any insight into pathophysiology and definitive aetiological link between CFS.
• Selection of population may reflect different prevalence in different geographical regions.
• Selection of CFS patients was from academic center rather than community based population.

Methodological strengths

• PCR products were then sequenced to ensure a match to MLVs.
• Testing for contamination with mouse DNA was performed and was negative.
• Repeat testing from a second set of blood samples was performed for a subgroup of patients and confirmed persistent PCR positivity.

Biases and conflicts of interests

Nil declared and none seem obvious.

Clinical relevance to primary health care

This article looks at basic science and demonstrates an intriguing association between chronic fatigue syndrome and MLV-related viruses. It should be considered as a basis for hypothesis generation and should not be considered demonstrating any clear evidence for aetiology.

It has no immediate clinical relevance for the management of chronic fatigue syndrome in the primary health care setting. However, some patients with CFS may be reassured that there is continuing scientific research in the condition.

References

1. Lo S-C, Pripuzova N, Li B, et al. Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors. PNAS September 7, 2010 vol. 107 no. 36 15874-15879

Editor: Michael Tam