Dr Ian Lipkin and his colleagues should be congratulated on the way in which they have co-operated in carrying out a very thorough piece of medical detective work.
This has found that there is no link between XMRV (xenotropic murine leukaemia virus-related virus) and pMLV (polytropic murine virus) and ME/CFS.
The results come as no surprise given what has happened since researchers at the Whittemore Peterson Institute first linked XMRV to ME/CFS in a paper that was published (but now retracted) in Science back in 2009.
All the initial hype that surrounded the publication in Science meant that people with ME/CFS were led to believe that a causative infection (ie XMRV) had been discovered, along with a diagnostic blood test, and that effective treatment with antiretroviral drugs would then follow.
Sadly, all three claims have turned out to be false hopes based on flawed science – with the scientific consensus now being that the original finding was due to laboratory contamination, probably from mouse DNA in the samples.
There should now be an apology – firstly from the laboratories who persuaded people to spend large sums of money on useless XMRV tests; secondly from those who influenced people with ME/CFS to put their health at risk by taking antiretroviral drugs.
ME/CFS is a serious neurological illness and there are many promising lines of biomedical research into the cause that need to be pursued, including the role of viral infections.
Contrary to the press headlines that are accompanying this story there is already a substantial amount of sound scientific evidence to show that a variety of viral infections (including enteroviruses, glandular fever, hepatitis and parvovirus) can trigger ME/CFS, that persisting viral infection may play a role in some people, and that reactivated viral infection (eg Epstein Barr virus and HHV-6/human herpes virus type 6) may also be playing a role.
Hopefully, we can return to more pressing research priorities now that the final chapter in the XMRV saga has been written.
Finally, it is encouraging to note that Dr Ian Lipkin is going to continue working in the area of ME/CFS research.
Dr Charles Shepherd
Hon Medical Adviser
The ME Association
September 18 2012
The results from the NIH multi laboratory study have been largely invalidated by the patient criteria chosen by the physicians. They chose to design a new unrecognised criteria only to be used in that study. Therefore these finding do not relate back to the Dr Mikovits and Dr Ruscetti’s discovery of MLV-related viruses in ME/cfs patients selected with the Canadian criteria and PEM. Nor does it relate to the four other positive ME/cfs MLV-related retrovirus papers.
However positive serology results in the multi laboratory study did prove that the MLV retroviruses have jumped into humans, because that serology test will only react to a MLV and not to a contaminant.
These scientists therefore need to offer no apology.
However REDLABS which sold tests licensed by the WPI board do need to present evidence that they clinically validated those tests as they claimed to have done. Both REDLABS and the WPI are responsible for those claims, not the scientists who’s shoulders they stood on.
The MLV-related retroviruses that have been repeatedly shown to infect people with ME, in five studies, need further investigation.
These viruses tend to only infect tissue not blood and infect below where PCR can detect them.
Furhter research will need to include next generation seuqencing which can detect MLVs that PCR cannot, tissue samples, and ME patients.
“There were some positive results returned by the NCI-Cornell-Mikovits team using another method that looked for antibody reactions to these agents.
Dr. Francis Ruscetti’s NCI lab tested serum from the coded samples using a flow cytometry-based assay slightly modified from the one he reported in the original 2009 Science paper.
The team detected antibodies in human serum but when the code was broken, it revealed equal numbers of CFS cases and healthy controls had these antibodies – nine in each group, or six percent of the subjects.
The paper states, “The serology results are more difficult to address given that the assay cannot be validated with plasma from humans with confirmed XMRV or MLV infection. We posit that positive results represent either nonspecific or cross-reactive binding and note that irrespective of explanation, a positive signal does not correlate with case status.”
Nonspecific, cross-reacting antibodies are common and can be the bane of many diagnostic serology platforms.
When serology assays for HIV were first developed, serum from healthy, non-HIV infected people sometimes contained antibodies that reacted with HIV proteins in the assay.
Blood transfusion studies showed that this non-specific antibody pattern did not correlate with transmission of HIV.[5]
It is this type of non-specific reaction that has led to development of HIV screening tests based on antibody testing; positive results from such tests are followed with other testing methods considered to be confirmatory.”
http://www.research1st.com/2012/09/18/the-de-discovery-of-xmrv/
You might also like to review the information (which echo’s the above) from Lipkin, (endorsed by Mikovits, Rusccetti and Alter) in the press conference now available as a recording:
http://cii.columbia.edu/blog.htm?cid=tM5E7V
Doh! I missed the key part from the Research 1st analysis of those positives. Apologies. Too hasty. It continued:
“To avoid drawing incorrect conclusions about the presence of virus based on the antibody reaction alone, it is imperative to use appropriate control experiments in parallel.
In the 2009 study and this multicenter study, a monoclonal antibody produced from a rat (7C10 rat monoclonal antibody) was used in the tests.
However, this particular antibody has been shown to cross-react with a number of other different viruses when it was originally produced in the early 1980s.[6]
As the authors indicate in the mBio paper, the fact that the positive antibody signal was found in equal numbers of CFS case and healthy control subjects’ serum is strong evidence that it is a sign of nonspecific cross reactivity with no clinical relevance.
It is also worth noting that study authors agreed in advance that the only “subjects with two positive results in the same sample type were considered positive for XMRV/pMLV.”
The 18 samples that tested positive by this method did not meet the stated standard for a “positive” result as agreed to by all the authors.”
Anyway, I hope that helps. It probably wont but there we go 🙂
The cohort was badly selected with a new unrecognised criteria and the patients could nominate controls, i.e. people who they had contact with. No patient was required to have the cardinal feature of ME.
The antibody to SFFV env has never cross reacted with anything. There is no study that can support the claim in the Cfids association post.
The people who tested positive by serology can only be infected with MRVs.
The scientists in the Lipkin study found people positive using PCR and serology. I think we can safely say now that people are infected.
” All gag-positive cDNA samples were negative for mouse IAP sequences. ”
http://me-advocacy.com/Lipkin_study_review.html