- Frank J M van Kuppeveld, associate professor experimental virology156,
- Arjan S de Jong, molecular medical microbiologist15,
- Kjerstin H Lanke, research technician156,
- Gerald W Verhaegh, senior research fellow26,
- Willem J G Melchers, molecular medical microbiologist156,
- Caroline M A Swanink, medical microbiologist1,
- Gijs Bleijenberg, professor psychology457,
- Mihai G Netea, professor experimental internal medicine35,
- Jochem M D Galama, professor clinical virology15,
- Jos W M van der Meer, professor internal medicine35
- 1Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, Netherlands
- 2Department of Urology, Radboud University Nijmegen Medical Centre
- 3Department of Internal Medicine, Radboud University Nijmegen Medical Centre
- 4Expert Centre for Chronic Fatigue, Radboud University Nijmegen Medical Centre
- 5Nijmegen Institute for Infection, Inflammation, and Immunity, Nijmegen
- 6Nijmegen Centre for Molecular Life Sciences, Nijmegen
- 7Nijmegen Centre for Evidence Based Practice, Nijmegen
- Correspondence to: F J M van Kuppeveld
- Accepted 16 February 2010
Objective The presence of the retrovirus xenotropic murine leukaemia virus-related virus (XMRV) has been reported in peripheral blood mononuclear cells of patients with chronic fatigue syndrome. Considering the potentially great medical and social relevance of such a discovery, we investigated whether this finding could be confirmed in an independent European cohort of patients with chronic fatigue syndrome.
Design Analysis of a well defined cohort of patients and matched neighbourhood controls by polymerase chain reaction.
Setting Certified (ISO 15189) laboratory of clinical virology in a university hospital in the Netherlands.
Population Between December 1991 and April 1992, peripheral blood mononuclear cells were isolated from 76 patients and 69 matched neighbourhood controls. In this study we tested cells from 32 patients and 43 controls from whom original cryopreserved phials were still available.
Main outcome measures Detection of XMRV in peripheral blood mononuclear cells by real time polymerase chain reaction assay targeting the XMRV integrase gene and/or a nested polymerase chain reaction assay targeting the XMRV gag gene.
Results We detected no XMRV sequences in any of the patients or controls in either of the assays, in which relevant positive and negative isolation controls and polymerase chain reaction controls were included. Spiking experiments showed that we were able to detect at least 10 copies of XMRV sequences per 105 peripheral blood mononuclear cells by real time as well as by nested polymerase chain reaction, demonstrating high sensitivity of both assays.
Conclusions This study failed to show the presence of XMRV in peripheral blood mononuclear cells of patients with chronic fatigue syndrome from a Dutch cohort. These data cast doubt on the claim that XMRV is associated with chronic fatigue syndrome in the majority of patients.
Contributors: FJMvK, MGN, JMDG, and JWMvdM designed the study and wrote the paper. ASdJ, KHL, GWV, and WJGM performed experiments and analysed the data. CMAS, GB, JMDG, and JWMvdM established the chronic fatigue syndrome patient cohort. All authors had full access to all of the data (including statistical reports and tables) in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. FJMvK and JWMvdM are guarantors of the paper and accept full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish.
Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that none of them (1) has support from companies for the submitted work; (2) has relationships with companies that might have an interest in the submitted work in the previous 3 years; (3) has spouses, partners, or children that have financial relationships that may be relevant to the submitted work, and (4) has non-financial interests that may be relevant to the submitted work.
Ethical approval: Ethical aspects of this study were approved by the Commissie Mensgebonden Onderzoek from Radboud University Medical Centre (CMO-1991).
Data sharing: No additional data available.
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