Innate Immune Changes in the Peripheral Blood

[Jonathan Edwards]

What is new though, is the idea that a defineable ME sub-group can be identified by an antibody test.

But I think we need to see that this is a empty idea unless the test marks some different biology in this group and the authors did not look for that. You can identify a defineable ME subgroup by having red hair or antibodies to tomato pollen. This is what I mean by not finding a story.

 

[Countrygirl]

Is it really possible that Dr Ruscetti who is regarded as The Father of Retrovirology would not understand antibody dynamics or tests?

 

[Jonathan Edwards]

Is it really possible that Dr Ruscetti who is regarded as The Father of Retrovirology would not understand antibody dynamics or tests?

Maybe Dr Ruscetti did not check the manuscript but it indicates a lack of knowledge of various aspects of B cell biology to my mind. Not understanding all the relevant aspects of immunology is pervasive even in immunology itself. I am afraid I think you have a touching but misplaced faith in scientists' ability to know everything!

 

[barbc56]

I don't know anything about Deborah Goetz and it wasn't my intention to be insulting. I thought the comments about her were an appeal to authority.

If someone would fill me in? If the subject is too personal to put in a post, just send me a PM.

However I think we can appreciate someone's struggles but still disagree with the person's theory. One doesn't really have anything to do with the other.

I agree that a student is often a reflection of what he/she has been taught.

Again, it's not personal.

Barb

 

[Ecoclimber]

The fact of the matter is that Milovits is discredited within the scientific community with her past actions concerning the fraud and manipulation of data with regards to figures and other factors not disclosed in the 2009 research published in Science. Many within the patient community are not aware of this activity but it is outlined in an article by an investigative reporter for the Chicago Tribune. Evidence of wrongdoing was presented to the editors of Science from information gathered by other well renowned retorvirologists. This information was serious enough that it required the retraction by the editors of the 2009 xmrv research paper in Science. The entirety ot the evidence was never made known to those within the patient community. Futhermoreo, Mikovits has claimed through various statements and exhibits that xmrv was the cause of ME/CFS, Lyme, GWI, Fibromyalgia, atypical ME, Autism without one scintilla of scientific research to back back up her claims. This is where she lost the scientific community. It is flawed since Mikovits could not base her claims and assertions on tbe results of any scientific research.

She is not the savior of this patient community but in fact has caused a great deal of harm to the point that mainstream researchers are reluctant to conduct any sort of research with this patient community after the considerable amount of malicious attacks on the reputations of those researchers. Mikovits association with the anti-vaxers movement, and the age of autism group have further alienated Mikovits with the mainstream scientific community.

Publication in a dubious journal https://en.wikipedia.org/wiki/Nova_Science_Publishers lends credence to this fact. The information provided as some sort of scientific abstract fails as it is a rehash of past research that meanders all over the place and appears as a shotgun approach hoping that one of assertions might hit the target. It is seriously flawed offering nothing specific that can construed as breakthrough in ME/CFS research. The scientific community will not even considered it worth reading. It is serious flawed and will have very little impact on cause of ME/CFS.

 

[Bob]

I sense that this thread is is about to go off-track, but I'd really like it to stay on-track and to remain focused on the science, and not the personalities or historic politics. As a group, we're never going to all agree about whether the XMRV saga was good or bad for this community; There are different opinions about it throughout our community. And we're never going to all agree about the character of the individuals involved in the XMRV saga. I have my own opinions about it all, but expressing them here will only cause divisions where we should be united in assessing the science and moving forward our understanding of the science. We've rehearsed the arguments, re XMRV, ad-infinitum. Let's move forward together with a friendly and constructive, but honest and critical look at the science, even where it makes us uncomfortable. We shouldn't be afraid of honest analysis. If the science stacks up then it stacks up. If the science has holes in it then I'd like to know about those holes and how they can be filled. Those holes are where the answers lay for us. As far as I understand it, Jonathan Edwards is focused on trying to understand the holes in the science in general. That's what he's focused on, for our benefit, so we shouldn't get offended when he points them out. We can politely disagree if we disagree.

 

[snowathlete]

I sense that this thread is is about to go of track, but I'd really like it to stay on-track and to remain focused on the science, and not the personalities or historic politics. As a group, we're never going to all agree about whether the XMRV saga was good or bad for this community; There are different opinions about it throughout our community. And we're never going to all agree about the character of the individuals involved in the XMRV saga. I have my own opinions about it all, but expressing them here will only cause divisions where we should be united in assessing the science and moving forward our understanding of the science. We've rehearsed the arguments, re XMRV, ad-infinitum. Let's move forward together with a friendly and constructive, but honest and critical look at the science, even where it makes us uncomfortable. We shouldn't be afraid of honest analysis. If the science stacks up then it stacks up. If the science has holes in it then I'd like to know about those holes and how they can be filled. Those holes are where the answers lay for us. As far as I understand it, Jonathan Edwards is focused on trying to understand the holes in the science in general. That's what he's focused on, for our benefit, so we shouldn't get offended when he points them out. We can politely disagree if we disagree.

Perfectly put. I agree.

 

[Jonathan Edwards]

I don't know anything about Deborah Goetz and it wasn't my intention to be insulting. I thought the comments about her were an appeal to authority.

However I think we can appreciate someone's struggles but still disagree with the person's theory. One doesn't really have anything to do with the other.

Barb

Quite agree Barb. It was just useful for me to know that this was written by a PhD student because that explains the rather unusual format, which might have contributed to my not getting the message. This sort of background does help get a fair view of what has been achieved.

 

[Ernie]

[1] Goetz, D.L.S. Cellular Immune Changes in the Peripheral Blood of Subjects Chronically Infected with XMRV. 128 (ProQuest, 2010). These data were submitted in partial fulfillment for Ph.D. requirements in October 2010 at University of Nevada-Reno

So ask why would Peterson and Ex-UNR scientist and Ex-WPI contractor Isabel Barao, PhD be given a grant for research that's already been done as seen above by Mikovits student at UNR. Where is Mikovits and her students data including all her UNR data and copies of her notebooks that have no intellectual property in them? Why are they hiding them from the taxpayers who paid for the research in them? Why are the WPI still submitting the cytokine patent every year that is Mikovits work? Their Founder is in prison for 3 felony convictions for using his employees as conduits! Just what else was he capable of doing to employees? Now there is some truth.

And the rest of the truth is coming soon so stayed tuned so you all get the facts and the proof to go with it! www.plaguethebook.com

 

[Ernie]

So does anyone feel like trashing this researcher too for publishing her chapter work in the same Nova Book? It's chapter V, and she did it as an abstract too. Oh and it costs $100.00 to access it:

Management of Chronic Fatigue Syndrome: Current Approaches and Future Directions (pp. 79-90) $100.00
Authors: (Samantha C. Johnston, Donald R. Staines, Ekua W. Brenu, Sonya M. Marshall-Gradisnik, Griffith Health Institute, School of Medical Sciences, National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Gold Coast, Australia)

Abstract:
Chronic Fatigue Syndrome, also referred to as Myalgic Encephalomyelitis
(CFS/ME) is a heterogeneous condition, with a complex clinical presentation. Patients
not only exhibit severe problems with fatigue following physical or mental exertion, but
often experience a diverse range of symptoms that all contribute to the debilitating nature
of the illness. Several pathophysiologies have been associated with CFS/ME, particularly
affecting the neurological, immunological, and autonomic systems though further
evidence is required to understand their exact role in CFS/ME. Patients present with
unique combinations of problems pertaining to these bodily systems, and may also
experience periods of recovery and relapse. The overall impact can also range from
significant reduction in pre-morbid daily activities and responsibilities, to the most severe
cases where patients may be bed-bound for prolonged periods of time and unable to care
for themselves. Altogether, these factors make CFS/ME a particularly challenging illness
to define and manage, and clinical guidelines vary significantly in their attention to
certain aspects of the disorder. Effective management of the illness needs to be highly
patient centered. While patients generally present to primary care health services, the
illness poses significant secondary risks to physical and mental health, particularly in
most severe, chronic cases. Hence, a multidisciplinary approach of clinicians is crucial
for providing additional support in management. The goal of this chapter is to review and
appraise several approaches for management of the illness. It is intended to be a reference
to both clinicians and patients to aid in reduction of the impact of CFS/ME.
https://www.novapublishers.com/cata...52281&osCsid=7b1b12f659d27182fddfb7cb1b28c88c

 

[Dx Revision Watch]

Abstracts for the 6 chapters of this Nova publication (for which Chapter 6 is open access) can be viewed on this page. The other 5 chapters are $100.00 if purchased individually, or $144.00 if purchased together:

https://www.novapublishers.com/cata...51424&osCsid=7b1b12f659d27182fddfb7cb1b28c88c

From the abstract for Chapter 1:

The Internist’s View on Myalgic Encephalopathy and Complementary/Alternative Treatments (pp. 1-16)
Authors: (Frank H. Comhaire, Brakelmeersstraat, Sint Martens-Latem, Belgium)

"...Conventional treatment must correct possible endocrine deficiencies and can help
alleviating particular symptoms. Causal treatment addresses the immune dysfunction
using corticosteroids, gamma globulin infusions, or immune-suppressors. Immune
modulators can selectively be attempted. However, treatment should also address the
pathogenic mechanisms by prescribing an appropriate diet, and particular food
supplements (Complementary and Alternative Medicine, CAM). We have developed a
specific nutraceutical containing several anti-oxidants (Astaxanthin, Oxido-reductase
ubiquinone Q10), a strong natural anti-inflammatory substance (pine bark extract,
Pycnogenol®), the fyto-adaptogen Lepidium meyenii (MACA), acetyl-carnitine, zinc,
and vitamins B6, B9 and B12. To this supplement long-chain poly-unsaturated omega-3
fatty acids are added (docosahexaenoic acid, DHA, and eicosapentaenoic acid, EPA).
The CAM approach induces and maintains improvement in 85% of patients, but it
seldom results in the complete disappearance of signs and symptoms..."

Edited to add:

Information on Prof Comhaire's nutraceutical Improve® in paper:

http://www.apjr.net/Issues/201203/PDF/1.pdf

Beneficial effect of food supplementation with the nutriceutical Improve® for the treatment of infertile couple. Frank H. Comhaire1*, Wim Decleer2

 

[Ernie]

Yes, the absence of things like sample size was another worry.

My first experience of ME research was the IiME8 conference in 2008. The first talk was by Greg Towers on XMRV. When I saw that a retrovirus was being considered in ME I was amazed, since it did not seem to add up on a system dynamic basis. I was not surprised when Greg said that he and others had identified the precise point at which sample contamination had occurred. I have subsequently read up about the XMRV story, although there will be a lot I do not know. I know that someone said that some of these people are not 'wet behind the ears'. However, most of us learn how to avoid perpetuating a mistake like that by doing more sets of blinded controls - it is not difficult. And when the blinded controls were done it turned out there was nothing there.

Yes, we all have some antibodies to everything on the planet and anything that might arrive on the planet from outer space but has not got here yet. The B cell system generates antibodies at random and there is sufficient cross talk between antibodies for all of us to show a little reactivity with everything. That reactivity may be increased a thousand fold after meeting an infection of course. So for some infections antibody levels are pretty reliable ways of indicating that you have met that infection. But for a mouse virus that as far as I know no human in infected with it is a bit hard to know what antibody levels could mean. The authors suggest some possibilities but their options indicate that they do not really understand antibody biology. They do not really answer the question.

Xenotropic MLV Envelope Proteins Induce Tumor Cells to Secrete Factors that Promote the Formation of Immature Blood Vessels – This 2013 research by Dr. Gary Owens of the University of Virginia provides evidence that envelope proteins on the surface of murine leukemia viruses can affect cancer progression. The article states, “The studies described herein address these questions, and show that at least one other XMRV-like virus exists, and that the virus evolved the ability to infect human cells and to express gene products that impact tumor pathogenesis. http://www.ncbi.nlm.nih.gov/pubmed/23537062

Frequent Detection of Infectious Xenotropic Murine Leukemia Virus (XMLV) in Human Cultures Established from Mouse Xenografts - This research from the well-regarded Dr. Adi Gazdar, suggests that the murine leukemia retroviruses may have the potential to become airborne. In their conclusion the Gazdar team warned, “Laboratories working with xenograft-derived human cultures should be aware of the risk of contamination with potentially bio-hazardous human-tropic mouse viruses and their spread to other cultures.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218386/

Generation of Multiple Replication-Competent Retroviruses through Recombination between PreXMRV-1 and PreXMRV-2 – This research from Dr. John Coffin and Dr. Vinay Pathak showed that replication competent murine leukemia retroviruses can be produced in a relatively short period of time. From their abstract, “To determine their potential to generate RCRs, we transfected PreXMRV-1 and PreXMRV-2 into 293T cells and used the virus produced to infect fresh cells; the presence of reverse transcriptase activity at 10 days indicated the presence of RCRs. http://www.ncbi.nlm.nih.gov/pubmed/23966380

 

[Ernie]

FDA has reviewed the currently available scientific information and has considered the public comments submitted to the Docket No. 96M-0311 and expressed at recent PHS-sponsored public workshops on xenotransplantation regarding the use of nonhuman primate xenotransplantation. Based on this review, and following consultation with the NIH, CDC, HRSA, and the DHHS Working Group on Xenotransplantation, the FDA has concluded that:

1. the use of nonhuman primate xenografts in humans raises substantial public health safety concerns within the scientific community and among the general public;
2. current scientific data indicates that human subjects, including individual xenotransplant recipients, their close contacts, and the public at large, would be exposed to significant infectious disease risk by the use of nonhuman primate xenografts; and that

Further scientific research and evaluation is needed in order to obtain sufficient information to adequately assess and potentially to reduce the risks posed by nonhuman primate xenotransplantation. This document is intended to provide guidance on nonhuman primate xenotransplantation. Xenotransplantation is defined for the purpose of this document as the use of live cells, tissues, or organs from a nonhuman animal source transplanted or implanted into a human, or used for ex vivo contact with human body fluids, cells, tissues, or organs that are subsequently given to a human recipient. For the purpose of this document, xenografts include live cells, tissues or organs from a nonhuman animal source used for xenotransplantation. This document provides guidance to industry concerning: (1) the potential public health risks posed by nonhuman primate xenografts; (2) the need for further scientific research and evaluation of these risks, particularly infectious agents;

Consequently, the recipient of a xenotransplant (includes cells, and cell lines) is potentially at risk for infection with infectious agents already known to be transmissible from animals to humans as well as with infectious agents which may become transmissible only through xenotransplantation and which may not be readily identified with current diagnostic tools. Infected xenograft recipients could then potentially transmit these infectious agents to their contacts and subsequently to the public at large. In this regard, infectious agents which result in persistent latent infections which may remain dormant for long periods before causing clinically identifiable disease are of particular concern.(1)

 

[duncan]

This is very complex for a layman such as me. Granular details aside, I was wondering if the paper/chapter's abstract relayed information that many here consider basic, but for me are important if only because I suspect their importance in the medical community has not been fully established.

For instance: Are innate immune system irregularities accepted as worthy of biomarker status yet for ME/CFSers, and if not, does this paper help towards that end?

Also, the concept of lower natural killer cell count/functionality - is this universally accepted as a biomarker? Klimas alluded to it years ago. Regardless, I'm not only uncertain if it is accepted, but I am unclear as to its implications. Does this paper help in that area? I have a dog in this race as my NK count was 5 in a range of 7-170. But what does that really mean? Do clinicians accept this as a deviation of note that is suggestive of disabling or even disruptive biology??

If this paper does either of these, or accomplishes other broad reinforcements to theoretical factors which help characterize ME/CFS or subsets therein, then I have to believe there is merit to this publication.

 

[thegodofpleasure]

Statement from Dr Judy Mikovits ( I have her permission to post it here)

It is clear from the Phoenix rising posts of Prof Edwards that he has misunderstood the data and the review article. It saddens me that Phoenix Rising and the scientific community continue to harm the patient community not because of bad since but because of conflicts of interest and bias that prevents an open and honest look at all of the data. It is clear that Professor Edwards upon perusal of the review misunderstood the data
The use of the SFFV Env antibody biomarker of this patient population adds clarity to an extremely heterogeneous diagnosis. This monoclonal antibody assay is based on the reactivity of sera/plasma from humans to the envelope protein of spleen focus forming virus (SFFV). This assay was extensively characterized over two decades and reactivity was specifically competed by the monoclonal antibody 7C10 in a dose responsive manner as published in several studies, all reference in the review article. This antibody detects all know polytropic and xenotropic gamma retroviruses and does not detect beta retroviruses including HERVK.

This assay was used is at least five cohorts and more than 800 patients and controls: in the original XMRV paper published in Science, in prostate cancer patients, in patients from the BEll, Cheney, Gordon, Montoya, Kamaroff, Lo/Alter, Hemispherx, and Silverman/Klein prostate studies. The assay was validated in the Lipkin multi-center study to detect a reactivity which was clearly not XMRV Silverman/DeRisi as XMRV Silverman/Derisi was clearly shown not to have a natural history of infection in man (or any animal so far). We discussed in detail what that reactivity might be and suggested further study

Dr Goetz thesis project was to characterize the immune responses in all of the studies described. We did all of the profiling on the attached overview of my program, including: the viral microarrays, KIR/NK genotypes, (Dr Kerr was to do his gene expression profile), multiplex cytokine profiling in all samples over more than five years
All of the numbers are detailed in the more than one hundred references..

It is also clear from the extreme dysregulation of the innate immune response and the response of study participants to various therapies discussed in the review article that using this biomarker in order to personalize medicine for not only the ME/CFS community but across, diseases such as CLL, prostate cancer, breast cancer, Chronic Lyme disease and CRIS due to mold (in collaboration with Dr Shoemaker)
We know from decades of work in Cancer, HIV/AIDS and HTLV-1 associated neurodegenerative diseases and cancer the importance of stratifying heterogeneous patient populations
Dr Goetz work in a significant advance in our understanding of a subset of at least 30% of all patients with a diagnosis of ME/CFS and the most aggressive forms of prostate cancer
The work even suggests simple and inexpensive experiments for Investigators to conduct in the rituximab study. Not every patient with CLL, MCL or multiple myeloma is a candidate for Rituximab so way should anyone thing anyone with a diagnosis of exclusion would respond to any single therapy. Cancer and AIDS patients use cocktails

Like you, I want all patients to get the best diagnoses and treatments possible..these data give ME/CFS patients several avenues for safe and effective treatments and all should be lauding Drs Goetz, Deckoff-Jones and Ruscetti for their persistence in publishing these data. More than five years worth of work which otherwise would have been lost to the ME/CFS (and other patient communities) because of the mistake in the original XMRV prostate cancer research. So much knowledge was learned in those studies. I am proud of my association with these people of integrity, who at great personal expense honored their commitments to the public health.

I will post to the MAR consulting website all data and powerpoints we have presented in my studies of ME/CFS and would be happy as always to explain in detail any further question you may have

 

[user9876]

Statement from Dr Judy Mikovits ( I have her permission to post it here)

Its a shame she doesn't join to debate and explain the results. If you are in touch with her why not suggest that.

When looking at comments people make on my papers I tend to think if people haven't understood the data maybe I haven't done a good job of explaining it.

 

[user9876]

Statement from Dr Judy Mikovits ( I have her permission to post it here)

Looking at this (which I don't have the background to understand I'm pulling out these as key statements

Statement1

The use of the SFFV Env antibody biomarker of this patient population adds clarity to an extremely heterogeneous diagnosis.

Statement2

This antibody detects all know polytropic and xenotropic gamma retroviruses and does not detect beta retroviruses including HERVK.

But from what is written I conclude that statement 1 is true iff ME or a subset is caused the set of viruses as defined in statement2

But this is a conjecture which I appreciate some people believe but it should be treated as a conjecture. But this seems to hang in the air unjustified but maybe it is justified in the paper that I've only quickly scanned.

 

[Kati]

Statement from Dr Judy Mikovits ( I have her permission to post it here)

t is clear from the Phoenix rising posts of Prof Edwards that he has misunderstood the data and the review article. It saddens me that Phoenix Rising and the scientific community continue to harm the patient community not because of bad since but because of conflicts of interest and bias that prevents an open and honest look at all of the data

Huh? Did I miss anything?
Patients are patients. There are no conflicts of interests or bias in the patient community excepts that we all want to get better.

Obviously Dr Mikovits is engaging with patients and is being fed information which turns groups of patients against another one. That's kind of sad.

 

[Bob]

Statement from Dr Judy Mikovits ( I have her permission to post it here)

Thanks for that, but it's a shame you couldn't simply ask Dr Mikovits for an explanation without stiring things up by unnecessarily accusing people of bias and of having vested interests. (Dr Mikovits' words are uncannily similar to yours, re 'bias' and 'vested interests', so I assume that she hasn't read this thread but simply responded to your accusations.) Why not just simply ask for an explanation without trying your hardest to cause bad feeling between members of the community? It does our community absolutely no favours to stir up resentment and bad feeling based on miscommunication and misunderstandings. Like we haven't got enough bad feeling in the community already, without stirring up more. I'm saddened to see such an effort to sow disharmony being carried out before my eyes on this forum, when the same efforts could have potentially seeded a constructive collaboration between scientists.

BTW, I think most of us on this forum see Dr Edwards as being exceptionally supportive, and open-minded, and here for the right reasons. That's certainly my opinion. I'm saddened that you have to make accusations rather simply engage in constructive dialogue, when Dr Edwards has made it abundantly clear (by his actions) that he's open and receptive to meaningful dialogue and engagement with our community.

 

[lansbergen]

As I recall it something in the patients serum reacted with an antibody Sandra used a lot in her research. Am I right or does my memory fail me?

My memory was right.