Article: Researchers on the Retrovirology Papers and XMRV: The Racaniello Twiv Podcast

Article: RResearchers on the Retrovirology Papers and XMRV: The Racaniello Twiv Podca

You can view the page at http://forums.aboutmecfs.org/content.php?316-Researchers-on-the-Retrovirology-Papers-and-XMRV-the-Twiv-Podcast

 

First off, thanks for another really good summary, Cort.

What about those Antibodies?They finally got to the big question the patients have been asking - what about those antibodies? Does THAT prove a real infection has occurred? Dr. Rein seemed to think yesprovided that another lab replicates those findings. (Dr. Mikovits has reported that Dr. Bagnis antibody test confirms the WPIs findings but that has not been published yet.) Of course many labs are developing their own antibody tests.

Which antibodies are we talking about? Antibodies produced by infected patients, or the antibodies to detect XMRV in culture? I had thought the NCI were working on developing an antibody test for XMRV, rather than confirming the presence of XMRV antibodies in patients.

The original antibodies used by WPI to detect the presence of XMRV in culture were developed for related Murine retroviruses, but also react to XMRV. I thought I'd read that the NCI used cloning techniques to make ultra-pure XMRV proteins, then developed an antibody against these proteins to produce a new antibody highly specific to XMRV. But this is not the same as detecting antibodies in patient blood.

In the WPI Science paper they talked about detecting antibodies to XMRV in the plasma of XMRV positive patient's blood. This is crucial because lab contamination can't account for antibodies in paitent's blood - which is what I think you're referring to. However, the Science test doesn't seem to be totally conclusive since again the test wasn't unique to XMRV: "These results are consistent with the hypothesis that CFS patients mount a specific immune response to XMRV".

Are the NCI working on both an antibody test for XMRV (testing for virus), and detecting human antibodies in patient plasma (testing for human antibodies against XMRV)? I'm a little confused, but then it's a ridiculously complex subject!

 

It is ridiculously complex.

I thought I'd read that the NCI used cloning techniques to make ultra-pure XMRV proteins, then developed an antibody against these proteins to produce a new antibody highly specific to XMRV.

I do remember that they isolated all the proteins and said they could use those to develop antibody tests - if I understand correctly.

My interpretation of Dr. Mikovits statement was that, yes, the NCI has developed their own test - which is more specific for XMRV - and that it validated that antibodies to XMRV were in positive ME/CFS patient samples from the WPI. That seems like a really big development! and I hope its correct. I would think a paper with controls and patients would be on its way. I asked Dr. Mikovits about that but haven't gotten an answer.

 

Ridiculously complex is right! It appears we're talking here about viruses that subvert and hide from organisms' immune defences, in an ongoing war with those immune systems, such that they end up getting written into the organisms' DNA and, if successful, become a part of organism itself. It's the stuff of life itself, the code of how we evolve, and this is the front line of that war, so we shouldnt expect it to be simple...

Regarding antibodies...I think it's been said that there's a theoretical indirect risk to the antibody findings based on the contamination theory, because if the XMRV were a contaminant, then the antibody tests are validated against that contaminant, so they might not be exactly what you think they are.

Doesn't really make sense to me, because surely the bottom line is: if patients, more than controls, are showing up on the antibody test, then they have to have antibodies to something, and whatever it is, even if not technically XMRV, precisely, that finding has got to be really significant and worth following up.

What's so extraordinary to me about the 'contamination theorist' side of the debate, is they seem to have no interest whatsoever in getting to the bottom of what's actually going on with the patients. Their only interest seems to be in shutting the whole area of research down, on technicalities that the results aren't exactly 100% what they appear to be, if they can. In other words, "Oh they can't have found XMRV, because that doesn't show up on standard single-round PCR, so whatever they did find, we should just forget about the whole thing". I just find their attitude impossible to comprehend, on a human level.

Anyway: if a reproducible antibody test can consistently find different levels in patients vs controls, then we are there, surely? Even if it weren't XMRV, it would have to mean something significant, and the question of what they are antibodies to would have to be answered.

Then again, we've been here before with biomarkers, high levels of viruses, documented immune abnormalities etc...and those lines of inquiry seem to have been spuriously suppressed just by grabbing a really wide sample of people with fatigue and finding that some of them don't have that marker so it "can't be the answer after all" - even though those same people also believe that the whole spectrum of CFS is a diverse ragbag of multiple different conditions that can't have one single explanation.

That's one of the biggest things I just can't square: how you can simultaneously be saying "X can't be the answer because it's obvious there isn't just one single answer to CFS" and yet also be saying "Y was clearly wrong because in our tests, not everybody has Y, so let's just forget about Y". And how does such illogicality get to survive?

Perhaps I need to read Catch-22 yet again! (Heller's my favourite author by the way, and all the rest of his novels are even better than Catch-22 IMO, so in passing I'll recommend Something Happened, Good as Gold, and God Knows, in particular).

 

I do remember that they isolated all the proteins and said they could use those to develop antibody tests - if I understand correctly.

My interpretation of Dr. Mikovits statement was that, yes, the NCI has developed their own test - which is more specific for XMRV - and that it validated that antibodies to XMRV were in positive ME/CFS patient samples from the WPI. That seems like a really big development! and I hope its correct.

Dr. Mikovits reported that Dr. Bagni was able to correctly identify 34/39 patients from the WPI

Just checked the Blood Working Group webinar: the NCI/Dr Bagni serology testing that was indeed to find human antibodies against XMRV ie evidence of an infection having taken place, which fits. The only downside is that in Phase llb of the testing NCI came up with a false positive serology test. Nothing is ever simple.

 

i don't believe alan rein at all. he painted himself into a corner now. everything he believes and says about xmrv is completely against Singh, Mikovitz, Klein, Silverman, Lo and alter. He's either 100% right or 100% wrong. something tells me, he ain't right!

 

He did state that you can't tell anything from the low genetic variation seen in XMRV at this early stage - which I thought was really helpful actually. I hadn't heard that. He also stated that the Hue paper's finding were overblown...So while he's not a fan - he is taking a middle road in several areas.