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Could the Epstein-Barr Virus – Autoimmunity Hypothesis Help Explain Chronic Fatigue Syndrome?

( Find a ‘quick’ summary at the  bottom of the blog)

 

The Epstein-Barr Virus Question in ME/CFS

We recently saw evidence suggesting that  increased viral loads of EBV (in whole blood) may be common in Chronic Fatigue Syndrome.We also saw that  ME/CFS patients  antibody responses to some proteins produced by EBV may be are impaired as well.

Those findings made sense given anecdotal evidence from doctors and study evidence from Dr. Lerner and Dr. Montoya indicating that  antivirals can be very helpful in some patients. Dr. Montoya’s recent review of anti-herpesvirus antivirals  indicated he believes they play a role but these results conflict with the Lipkin/Chronic Fatigue Initiative study which found almost no active herpesvirus infections in either Dr. Montoya’s or in the CFI’s study groups.

smoldering fire

Some researchers think the tests used by Dr. Lipkin are not sensitive enough to pick up the kind of ‘smoldering’ infection they believe is found in ME/CFS

How to reconcile these findings ? Kristin Loomis of the HHV-6 Foundation and Dr. Chia have stated that while the method Dr. Lipkin used to detect herpesviruses (in plasma) works very well in people with highly active herpesvirus infections, they do not believe it would pick up the type of smoldering, lower-level infection suspected in ME/CFS.

The existence of that ‘smoldering infection’ is, of course, controversial. It’s possible, even probable,  that most researchers outside this field including Dr. Lipkin do not believe that such a small infection could have such serious consequences.

Indeed, the ‘increased viral loads’ in the German study did not indicate a highly active infection was present, but they were still significantly higher in the ME/CFS patients than in the controls. Dr. Lerner, Kristin Loomis and others believes that’s significant and that’s the result they believe Dr. Lipkin would have received if he had used a different technique.

After XMRV it’s no surprise to see controversy in the pathogen field. The bottom line is that EBV is still a possible culprit in ME/CFS. Given that and the Rituximab findings suggesting that an autoimmune component may be present in ME/CFS, let’s look at a fascinating hypothesis that ties EBV infections and autoimmunity together and could have implications for ME/CFS.

Epstein-Barr Virus and Autoimmunity

CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis. Pender MP. Autoimmune Dis. 2012;2012:189096. doi: 10.1155/2012/189096. Epub 2012 Jan 24.

If this hypothesis is right, Epstein Barr Virus – still the virus most closely associated with ME/CFS – has a very, very close connection to autoimmune disorders.

EBV

Pender believes an EBV infection of B-cells sets the stage for autoimmunity in people with impaired T-cell responses

About a decade ago Michael Prender proposed being exposed to EBV is a prerequisite for having autoimmune disorder. In doing so he tossed aside the usual EBV mimicry hypothesis; that proteins found in EBV confused the immune system into attacking the body and put forth a much encompassing idea. He proposed that EBV’s residence in B-cells – which are ground zero for an autoimmune response – was responsible for most types of autoimmunity. His hypothesis, a decade later, remains alive  and well.

B-cells produce antibodies and autoantibodies. As we learned in the Rose autoimmune talk, the production of autoantibodies primed to attack the body is a natural outcome of an immune system that must defend the body against microbes containing proteins that are very similar to those found in humans. The immune system has ways to deal with these autoantibodies and in most cases it succeeds. When it doesn’t you have an autoimmune problem.

An Admiring Look at a Virus

In some ways you’ve really got to give it up to Epstein-Barr Virus (EBV). EBV  just happens to be the only virus known to survive in B-cells. In fact, EBV doesn’t just survive in B-cells they are its home. Somehow B-cells have managed to thrive survive in the  very cells that are designed to attack them.  That takes a special kind of viral hutzpah..

Every time EBV infects a B-cell it tells it to reproduce and when the cells does, EBV inserts itself into the B-cell’s ‘germinal center’ where it will reside, largely untouched, for the rest of the B-cells life. Every time the B-cell replicates EBV hijacks its reproductive machinery to produce more EBV virions.

EBV

EBV – A remarkable virus

Because B-cells aren’t long-lived and because EBV can’t replicate in them when they’re pumping out antibodies, EBV has found ways to keep B-cells alive and in a state of latency for longer and longer periods of time.

EBV has found ways in induce B-cells to undergo what’s called ‘clonal’ expansion in which B-cells produces EBV infected clones of themselves. One way EBV does this is by tricking the immune system to believe an pathogen is present, thereby causing it to ramp up B-cell production.

Keeping the immune system on high alert, though, can cause problems. Think of our missile defense system. If it’s on high alert the risk of a catastrophic mistake  increases greatly, and here is where Pender and his hypothesis comes in.

Cytotoxic T-cells and A Numbers Game

“CD8+ T-cell deficiency would appear to be a general feature of human chronic autoimmune diseases. ” Pender et.al.

EBV infections in the body are usually tightly controlled by killer or cytotoxic T-cells (CD8+ T-cells). These CD8+ T-cells kill EBV infected B-cells when they proliferate.

cytotoxic t-cell

Pender believes reduced cytotoxic T-cell functioning plays a key role in EBV triggered autoimmunity. Some evidence suggest cytotoxic T-cell functioning is reduced in ME/CFS.

Pender and other researchers believe an inherited defect in cytotoxic T-cells that prevents them from controlling EBV may be behind a lot of autoimmunity. (A Simmaron Research Foundation project involves looking for inherited problems in T-cells, B-cells and NK cells killing capacity.) It turns out that a long list of autoimmune disorders are, in fact, characterized by low cytotoxic T-cell levels.

In what is essentially a numbers game, Pender believes that poorly functioning cytotoxic T-cells allow more EBV infected B-cells to proliferate. Because EBV induces these B-cells to proliferate at a higher than normal rate the outcome of a less controlled EBV infection is simply more and more B-cells. That means more autoantibodies (remember they’re a natural feature) for the immune  system to filter out, and more possibility of a catastrophic mistake being made; i.e. a full-blown autoimmune or autoinflammatory disorder.

Cytotoxic T-cells and Chronic Fatigue Syndrome

CD8+ T-cells have not received a lot of attention in ME/CFS, but early evidence suggests they’re not working too well. A recent German study found a reduced frequencies of an EBV specific T-cells  in people with Chronic Fatigue Syndrome and an Australian  group found reduced cytotoxic T-cell (and NK cell) killing capacity in ME/CFS.

In fact, given the similarity in the killing systems in cytotoxic T-cells and NK cells, it wouldn’t be surprising to find the same dysfunction in both NK cells and CD8+ T-cells.  (If your NK cells aren’t doing so hot, it’s possible your cytotoxic T-cells aren’t doing so well either.)

If that’s true, your cytotoxic T-cells may not be taking out as many EBV infected B-cells as normal. That fits Pender’s hypothesis to a T.

Another Numbers Game

Timing could be everything in EBV, ME/CFS and autoimmunity.   An EBV infection in young children usually doesn’t cause symptoms. It turns out that infants have very high levels of cytotoxic T-cells that allow them to stop the virus in its tracks.

By age sixteen, however, those cytotoxic T-cell levels are a third of what they were at age two. That means that an infection which most infants wouldn’t even notice often causes infectious mononucleosis (glandular fever) and a greatly increased risk for ME/CFS and multiple sclerosis in adolescents.

from youth to old age

Being exposed to EBV later in life greatly increases the difficulty the body has in fighting it off. How many people with ME/CFS were first exposed to EBV later in life?

It appears that the Western fanaticism with cleanliness is pushing the date most children are exposed to EBV further and further forward. In the developing world most children are exposed to EBV by age three, and almost 100% are exposed by age ten, but some studies suggest about half the children in the developed world  have not been exposed to EBV by the time they’re ten.

As many as 50% of these children may come down with a symptomatic, infectious mononucleosis-like illness and during that illness as many as half of B-cells in their blood may become infected with EBV  -  producing a huge reservoir of highly active EBV infected B-cells.

The Jason Northwestern ME/CFS study estimates as many as 10% of college students will come down with infectious mononucleosis. The increased IgM antibody rates in the ME/CFS patients in the German study suggested they may have been suffering from a primary (first-time) infection as well.

Data is lacking on date of first time EBV infection in ME/CFS, but the German study with its high IgM levels  suggests a substantial number of ME/CFS patients may have encountered EBV later in life when their immune systems are less prepared to deal with it. Could ME/CFS in some people simply be the consequence of encountering EBV later in life?

Pender ties in other autoimmune factors, many of which are found in Chronic Fatigue Syndrome as well.

Heritability

Autoimmune disorders are have a higher degree of heritability than most disorders – an intriguing factor given that cytotoxic T-cell functioning is largely governed by heredity.  The heritability factor in ME/CFS and Fibromyalgia has not been the subject of many studies, but one study suggests that heritability may be even higher in these disorders than in autoimmune disorders.

Location and the Vitamin D3 Connection

Living further from the equator also increases the risk of autoimmune disorders such as multiple sclerosis and rheumatoid arthritis. Reduced sunlight and vitamin D3 could aggravate  cytotoxic T-cell problems thus imperiling control of EBV. It turns out that cytotoxic T cells contain more vitamin D3 receptors than any other immune cell.

Dr. Bateman was astonished at how low the Vitamin D3 levels were in her ME/CFS and FM patients but people with ME/CFS and FM probably get less exposure to sunlight than do healthy people. People who are bedridden, of course, get very little exposure to sunlight.

Gender

Cytotoxic T-cells are believed to be hormonally regulated (with increasing estrogen reducing Tc levels) and women tend to have fewer cytotoxic T-cells than men. The gender imbalance found in FM and ME/CFS as another.

Reduced cytotoxic T-cell functioning, high heritability, reduced vitamin D3 levels, and female predominance all appear to be present in ME/CFS and all fit Pender’s paradigm for an EBV induced autoimmune disorder.

Treatment

Rituximab

Rituximab is high on Pender’s list of treatment options for people with EBV induced autoimmunity

Pender’s treatment recommendations for EBV triggered autoimmune disorders are enticing given what we know about Chronic Fatigue Syndrome. They start with none other than Rituximab.

“Improvement of an autoimmune disease with rituximab therapy would be consistent with an essential role of EBV in the development of the disease”

Pender asserts an EBV triggered autoimmune disorder could be treated in two ways.

(1) Depleting B-cells with monoclonal antibodies such as Rituximab would reduce total B-cell levels which would reduce the levels of EBV infected B-cells and autoantibody production. ( Since Rituximab would also reduce the levels of non-EBV autoreactive B-cells a successful course of Rituximab does not constitute proof.)

(2) Boosting immunity to EBV – Getting EBV under control is another option.

  •  the gp350 vaccine – vaccinating young adults with recombinant gp350 has been shown to stop the development of infectious mononucleosis after EBV infection. If Pender is right, gp350 vaccination could be one way of cutting down ME/CFS rates in adolescents. This would simply require determining which adolescents have not been exposed to EBV and vaccinating them. Given that Jason expects perhaps as many as 10 percent of college freshman to come down with some form of infectious mononucleosis this would seem to be a really good idea.
  • using monoclonal antibodies against gp350.
  • Intravenous infusion of autologous EBV-specific cytotoxic CD8+ T cells after expansion in vitro
  • interleukin-7, which expands the population of functional virus-specific CD8+ T cells in chronic viral infection

Summary

  • Michael Pender, has proposedthat exposure  to Epstein-Barr virus, a virus that takes up residence in the B-cells, is required for autoimmunity.
  • All B-cells produce autoantibodies that would, if the immune system didn’t filter them out, attack the body.
  • EBV prompts B-cells to produce EBV infected B-cells which live longer and produce more B-cells than usual. Their longer lifespan and higher productivity means EBV infected B-cells also produce more autoantibodies than normal B-cells.
  • Pender believes high numbers of autoantibodies produced  by these B-cells overwhelm the immune system causing an autoimmune disorder.
  • The key problem in autoimmunity Pender believes, then, is large numbers of EBV-infected B-cells.
  • Since cytotoxic T-cells kill EBV-infected B-cells, a poor cytotoxic T-cell response may be the key, and indeed reduced cytotoxic T-cell responses appear to be common  in autoimmune disorders.   (Two studies suggest reduced cytotoxic T-cell responses are present in ME/CFS  as well.)
  • Because cytotoxic T-cell responses decline over time, someone exposed to EBV as an adolescent typically has a much more difficult time fighting off EBV than a young child does. (Could late exposure to EBV be a common feature in Chronic Fatigue Syndrome?)
  • ME/CFS shares  factors like low Vit D3 levels,  a high degree of heritability and gender predominance with autoimmune disorders.  All these plus the increased EBV viral loads, the reduced antibody response to the latent stage of EBV and the possibly reduced cytotoxic T-cell functioning suggests ME/CFS could very well fit Pender’s hypothesis of an EBV triggered disorder.

Conclusions

The role Epstein Barr virus or autoimmunity plays in Chronic Fatigue Syndrome is unclear, but Pender’s hypothesis suggesting that poorly controlled EBV infections cause many autoimmune disorders is intriguing given recent study evidence of increased EBV viral loads in ME/CFS.  Time will tell but the  reduced cytotoxic T-cell functioning, gender imbalance, the low Vit. D3 levels, the high heritability factors, and the positive response to Rituximab reported all suggest Pender’s EBV/autoimmune hypothesis is something we should keep an eye on.

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63 Comments

  • Lisa Petrison

    May 4, 2014 at 8:34 pm - Reply

    >Michael Pender, has proposed that exposure to Epstein-Barr virus, a virus that takes up residence in the B-cells, is required for autoimmunity.

    I would think that this would suggest that if ME/CFS is an autoimmune disease, all patients with the disease would be EBV+.

    That is not the case though. Even if we are looking at the most carefully screened and thoroughly tested patients asked to be prototypes from the Incline Village epidemic, not all were EBV+.

    So unless he is proposing that the EBV test is inaccurate (when it shows up negative on repeated occasions over a period of decades), then it would seem that either ME/CFS is not an “autoimmune disease” or his hypothesis is wrong.

    • Victoria

      June 18, 2014 at 7:48 pm - Reply

      I am 62 yrs old. I was diagnosed with CEBV at age 34 but my initial outbreak was at age 27. That name was later changed to CFS. I started having remissions of the CEBV and eventually it stopped being active. My diagnosing Dr. checked me using Titers. His name was Dr. James C Laidlaw from Winchester, VA.

      • Nick in Coventry

        September 11, 2014 at 5:00 pm - Reply

        I had EBV in my early twenties and was very very unwell from it. However my personal feeling is that it has less to do with any particular virus and and more to do with a level of infection. A trigger of some description, Virus, Bacteria or any other sets the immune system off and it refuses to calm down. Lyme disease is so similar to CFS, post polio syndrome all of these things are similar with different initial enemies triggering the response which is autoimmune. There’s more to it than this but I’m certain this is the basic mechanism at work.

        • Victoria

          September 16, 2014 at 11:15 am - Reply

          An allergic reaction that was never treated caused my throat to hurt so that I couldn’t sleep unless I sat up at night. From there I was freezing cold at night and so hot during the day that I had to sit on a towel due to the sweating. I had no fever and being young and money being tight, I didn’t go to the Dr. at first. I broke out in a rash and my eyes were very bloodshot and my face was so red it looked like I had a bad sunburn. I was reddest across my nose and top of my cheeks like the Lupus mask and it has never completely left my face, even after all these years. My Dr. just told me to rest and very much so until the rash was completely gone. I never received any meds. I was 27 at this time. I was an at home Mom at the time. I didn’t have problems again until I worked in the evenings and took care of my then 2 year old son during the day. I got really tired and run down. Lost weight no matter what I ate. We moved to the Carolinas when my son was 4 and by then I knew something was very wrong. I didn’t work and could not get rested up again. Started having headaches and allergies that I had never had before. Was not diagnosed until age 34 when we moved back to VA.

  • Cort Johnson

    May 4, 2014 at 9:07 pm - Reply

    Because ‘some’ people with ME/CFS test positive for an active EBV infection and others do not, does not mean that his theory doesn’t apply to that subset of patients. ME/CFS is such a heterogenous disorder – as it has to be given the symptomatic defiinition – that nothing will apply to everybody.

    Then there’s the question of how to accurately diagnose an active EBV infection. The German researchers would suggest you need to do PCR on whole blood. I’m not clear how many studies have done that.

    • Lisa Petrison

      May 4, 2014 at 9:39 pm - Reply

      Here’s a quote from a highly respected epidemiologist who commented on Julie Rehmeyer’s presentation about ME/CFS a couple of months ago at the Santa Fe Institute:

      >There’s a science that studies the causes of disease, epidemiology. A way that you could use a lot of these ideas is that you come up with an adequate case definition. That’s hard. You start by identifying true cases and matched controls, and you can go through and create hypotheses. For instance, about mold exposure. Where you’ve lived in the past ten years. Then you come up with nice identifiable risk factors for this disease. Like with the AIDS epidemic. You had this collection of individuals who had Kaposi’s sarcoma and pneumocystis, but you had no idea what caused it. They sat down and had this clear case definition that you can try to tease apart from there. It’s surprising to me, and I guess it’s because it’s such a nebulous thing, that no one’s ever sat down and done this.

      http://paradigmchange.me/wp/?p=672

      It is true that “CFS” (as defined by the CDC) is an unfortunately heterogeneous entity. The reason for that is because no one ever has done the sort of basic study that this epidemiologist is suggesting should be the very first step in trying to understand any disease, and because the CDC defined the disease very broadly.

      The Incline Village cohort was not heterogeneous, however. Patients there were impacted at various levels of severity, but the actual illness (including laboratory markers and illness course, e.g. with a 0% recovery after 25+ years and high rate of NHL according to Dr. Peterson) was quite homogeneous. And there are very few knowledgeable people in this community who would suggest that insofar as we are talking about “true cases,” the patients from the Incline Village outbreak (and particularly the ones selected by Dr. Cheney and Dr. Peterson to be prototypes for the illness they were studying) would not be at the top of the list of those who qualify.

      Despite the fact that this sort of epidemiological work into profiling “true cases” should have been done 30 years ago, it is not too late to do it now. Its not having been done is integral to the problem of the disease being based wholly on symptoms and defined ridiculously broadly — a problem that is never going to go away until we look closely at some true cases.

      I feel strongly enough about this issue that I made a short video on the topic.

  • Firestormm

    May 4, 2014 at 9:21 pm - Reply

    “Epstein Barr Virus – still the virus most closely associated with ME/CFS”

    In what way? And is it not also the virus most commonly associated with most people? Thanks!

    • Cort Johnson

      May 4, 2014 at 11:19 pm - Reply

      In a bunch of ways.

      More studies have been done on EBV in ME/CFS than any other virus. The German study found elevated viral loads and problems with the immune response to EBV in ME/CFS patients but not healthy controls. Glazer has found evidence of that early proteins are sparking an immune response in ME/CFS but not controls and infectious mononucleosis – which is usually caused by EBV – is a known and common trigger of EBV. Lerner commonly finds EBV reactivation in his patients (other researchers do not agree on what constitutes reactivation).

      All in all, EBV ‘reactivation’ is more associated with ME/CFS than any other herpesvirus or other virus. I’m not saying that it’s causing it or not causing it; I’m more saying that historically it’s been more associated with ME/CFS than any other virus.

      Granted it’s still a pretty muddy issue all around. :)

  • Lolly

    May 4, 2014 at 9:31 pm - Reply

    I was diagnosed with CFS in the 1980s because as the time, chronic EBV was synonymous with CFS. I would be happy to hand the CFS diagnosis over to the mold people and anyone else who wants it so that I can get appropriate treatment for my chronic EBV infection.

  • BONNIE J.

    May 4, 2014 at 9:57 pm - Reply

    CORT, I’M WONDERING IF YOU’VE HEARD OF UNDULANT FEVER? MY BROTHER & I WERE VERY ILL WITH THIS WHEN I WAS 6. I BELIEVE IT RECURRED FOR MANY YEARS UNTIL I GOT CFS AT 57. I ALWAYS GOT EXTREMELY HIGH TEMPS & WOULD TAKE LONGER TO RECOVER FROM FLUS THAN OTHERS. I NEVER HAD A LOT OF ENERGY & WOULD GET FATIGUED MORE & MORE AS I GOT OLDER. I BELIEVE I RAN ON ADRENELIN FOR YEARS!! I WAS A HYPER KID WITH LOW ENERGY LEVELS!

    • Cort Johnson

      May 4, 2014 at 11:13 pm - Reply

      No I haven’t but it doesn’t really matter; the Dubbo studies indicate that any severe infection can probably be a triggering even for ME/CFS. The astonishing thing was that bacterial or very different viral infections, given enough time in the right (wrong) person, seemed to result in similar cases of ME/CFS.

      • Angela

        May 4, 2014 at 11:41 pm - Reply

        It’s Brucellosis.

      • Nick in Coventry

        September 11, 2014 at 5:21 pm - Reply

        An exhausted yet overactive immune system could be caused by many factors, and taking antivirals wouldn’t cure the patient of ME/CFS. If antivirals cure CFS then my theory is wrong and there is a cure for us. I think it might be possible to kill the trigger of the chronic fatigue without curing the patient of CFS/ME. I was bitten by a tick in a Lyme disease area, I squeezed it off me pumping the contents of it’s stomach into my blood system, I had EBV in my early twenties, Herpes 1 and 2 and don’t forget repeating Malarial fevers, all of these could have triggered CFS. Lets not forget that Glandular Fever, cold sores in embarrassing places or on the faces of schoolkids and certain childhood illnesses are all viruses in the Herpes family. However Lyme is bacterial and malaria parasitic protozoans.

  • nancy

    May 4, 2014 at 10:36 pm - Reply

    What is the best treatment for eliminating re-activated EBV? Has anyone tried the approach suggested by Dr. Pridgen such as combining Celebrex and Valtrex? I am immune deficiency and don’t have any experts in CFS/ME, EBV or anything where I live. I need a good doctor recommendation. Thanks.

    • Hope H.

      May 6, 2014 at 8:45 pm - Reply

      Dr. Pridgen’s protocol turned out not to be Celebrex and Valtrex. His first most successful treatment is Famvir 500mg twice a day with Celebrex 200mg twice a day. I just started it a few days ago. I’m really helping that it helps so many of us. I’m still not sure why he hasn’t let the cat out of the bag to the public as to what he is using because he is giving it to his patients and telling other doctors who are willing to treat their patients with his protocol.

      Hope

      • nanc

        May 6, 2014 at 9:32 pm - Reply

        Wow, thank you for reporting this. I am seeing my immunologist next week. I have had success with Valtrex, but need an anti-inflammatory. Please keep us posted on how you are doing. Thanks again!

    • Sharon

      May 9, 2014 at 1:58 pm - Reply

      Had fibro for years. Following a protocol Radio did, (on Phoneix Rising site) using Lipid Replacement Therapy & other things (he recovered, so I figured he must have done something right).

      Also started Dr. Pridgen’s protocol., but my fibro doc said Valcyte is stronger.

      EBV plays some part in this disorder because just had blood tests run & EBV high. Had mono as a teen.

      Feeling wiped out, but figure it may be a good thing – that something I’m doing is working.

  • Andrew Gladman

    May 4, 2014 at 10:52 pm - Reply

    The trouble here is I think that people ‘want’ it to be EBV despite the evidence not being there, in fact there is now quite a lot of evidence to the contrary – I feel that ignoring all of the results of previous scientists because of supposed test shortcoming when the test used were much more thorough than what is normally used is grabbing at straws somewhat. I feel like concentrating on one virus like this is the research equivalent of treading water. I’m of the opinion that EBV is a common trigger of ME/CFS but as are a lot of other viruses, bacterial infections, sudden acute stress and a whole host of other things (not forgetting vaccinations of course.) Now that said I think autoimmunity is the absolute correct line of thought, to my mind we should be concentrating on the ongoing autoimmune problem rather than the trigger of illness. As in a forest fire, the triggering illness is simply the spark that set the forest ablaze – at that point the blazing inferno is the problem not the spark which has long since dissipated.

    • Cort Johnson

      May 4, 2014 at 11:25 pm - Reply

      You may be right. Cheney gave up on chasing infections long ago. I do think that some people get much better on antivirals but the fact that so many pathogens can spark ME/CFS does suggest that the immune system is the problem. It’ll be interesting to see what Pridgen comes up with, though.

    • Lolly

      May 5, 2014 at 3:05 am - Reply

      It’s ridiculous to think that anyone “‘wants’ it to be EBV”. Recent studies have found that some people who are chronically ill have difficulty suppressing EBV infection. For those of us who became chronically ill following onset of EBV in the 1980s and who have titers in the thousands along with positive IgM, it makes sense to look at what is actually there instead of trying to come up with some kind of consensus for everyone who has ever been diagnosed with CFS.

      • Angela

        May 5, 2014 at 3:34 am - Reply

        I “want” it to be whatever it is or isn’t. Just figure it out already. I don’t want my Drs guessing and throwing powerful drugs at me that make me feel like death and are poison to my poor liver; when they aren’t sure what I truly have.

  • Angela

    May 4, 2014 at 11:48 pm - Reply

    How do you know EBV is active, reactivated or simply in the past? I have high positive IGG EBV VCA and EBV Nuclear AG (EBNA) AB IGG, but negative on every other EBV test. No one can tell me what that means. There’s sooo much confusion. How can all of these viruses be “Past Infection” when you were never diagnosed with an Active infection in the past?

    • Cort Johnson

      May 5, 2014 at 12:10 am - Reply

      I can tell you there’s no consensus on EBV. I don’t know what the doctors would say to your results.Montoya had this critieria for entry into an antiviral study : h HHV-6 and EBV and had elevated HHV-6 and EBV antibody titers (median titers: EBV VCA IgG 1:2,560, HHV-6 IgG 1:1,280)..

      You fit the EBV parameters.

      • Angela

        May 5, 2014 at 3:36 am - Reply

        Thanks for that info Cort.

  • TERRY

    May 5, 2014 at 3:11 am - Reply

    follow

  • Paul

    May 5, 2014 at 6:00 am - Reply

    Whilst, historically, medical research has been quite successful in discovering simple correlations between infection and disease, it has been much less so where the cause and effect relationship is more complicated and perhaps involves more than one pathogen / infection. Indeed, we know little about the full implications for human health of many potentially immune system draining viral / retroviral infections.
    As Lisa P pointed out earlier, AIDS is just such a case in point. But how many people had to die before that disease was taken seriously and the HIV virus was identified?
    In the case of ME/cfs, the existence of another (as yet unidentified) immune system depleting pathogen (or genetically determined condition), remains a distinct possibility and in such circumstances, the existence of a coincident smouldering EBV infection, would be a significant factor. Discovering which comes first, the cart, the horse, the chicken or the egg and whether any (or all) of them is irrelevant, is a difficult conundrum.
    What we do know is that the “low-hanging fruit” has been plucked from the research tree and what remains is likely going to be infinitely more challenging to discover in the future.

    • Lolly

      May 7, 2014 at 4:18 pm - Reply

      In NYC AIDS was taken pretty seriously, and btw, AIDS appeared in the same group of gay man that had recently been vaccinated with an experimental Hep B vaccine. EBV was discounted as “the cause” of CFS when not all patients diagnosed with CFS tested positive for EBV. Instead of allowing those with EBV to keep a chronic EBV diagnosis, they were tossed instead into the hellpit that is the CFS diagnosis. The chronic EBV diagnosis was disappeared and replaced with the Holmes CFS definition, which was replaced with increasingly more meaningless definitions. Chronic EBV is quantifiable, but the diagnosis no longer exists. Until recently researchers insisted that it was not possible to have a chronic EBV infection without dying. HHV-6 infections have also discounted. The “low-hanging fruit” hasn’t been “plucked”, it’s been ignored.

  • phillida bunkle

    May 5, 2014 at 10:01 am - Reply

    Treatment worth a try? I have just been to a nutrition seminar by British nutritionist Antony Hayes ofBritish company Nutri-Link. He had a patient with strange unexplained symptoms,with autonimmune issues which did not, however, fit the usual CFS pattern. She had had Epstien Barr in the past. He had her tested for total viral load via Doctors Data labs. This showed some occult virus activation so he went with the idea she might have chronic EP infection. He treated with 6 weeks of Olive Leaf extract ( form American supply Allergy Research) alternated with 6 weeks of orangano oil (also from Allergy research I think) . These are antimicrobials which avoid the gut problems of most antibiotics. After 18 months she had no side effects from the treatment and total freedom from symptoms. Low risk and worth a try.
    Phillida

    • OM

      May 6, 2014 at 10:50 pm - Reply

      Interesting idea, but what doses were given and how often? Would love to know more details.

  • Cabinfeverjen

    May 5, 2014 at 4:17 pm - Reply

    This “thing” has a dozen names, Valley Fever, glandular fever….. I can’t even grab them all of the top of my head! Evidently its FAR more common then they would like to portray.

  • Sarah R.

    May 5, 2014 at 7:46 pm - Reply

    Great info, Cort. The summary is especially nice.

    As a person who responds well to antivirals, and one who has a history of mono as a teenager, the EBV reactivation hypothesis resonates with me intuitively. I don’t think my immune system has been very strong ever since I had mono. But I didn’t come down with full-fledged ME/CFS until my 50′s. I would so love it if more studies show something definitive. I want to get well before I’m 80!

  • VitDdefnPNW

    May 6, 2014 at 1:43 pm - Reply

    My son and I have allergies/asthma, and he and I catch stuff more easily and remain sick longer than my husband and daughter who have no atopic conditions. Do some/most/all folks with ME/CFIDS have allergies of some kind? Could it be that research should focus more on the immune system itself rather than viruses? And perhaps more specifically, gut health?

    What I’m getting at is, science has confirmed that tree pollen is a potent source of allergic reaction…in some individuals, but not all. So, does it make sense to conclude that pollen is NOT a cause of misery? No, but neither does it make sense to try to pin every atopic woe on pollen. Rather, we know that something about every sufferer’s immune system is common, whether the trigger is pollen, cats, dust mites, mold, etc. What is that “something” and could it be the key to figuring out ME/CFIDS?

    • Sharon

      August 1, 2014 at 8:47 pm - Reply

      Interesting – I also suffer with allergies to many things. Dr. Tintera, an allergist once said “there are not different allergies, just different adrenals – impaired.

      Has anyone tried aggressively dealing with allergies – getting shots etc? I’ve read one of the theories of these disorders is allergies.

  • R.A.Perill

    May 6, 2014 at 11:49 pm - Reply

    Yes, Sarah, it would be nice to die healthy!

    • Sarah R.

      May 7, 2014 at 5:59 am - Reply

      Yeah, R.A.Perill, you made me laugh with that comment. I did think after I posted that as long as I’m wishing, I ought to want to get well tomorrow, or even today! But a cure seems so far away. I was figuring 80 might be possible… only 19 more years to go!

  • Eilidh Hewitt

    May 8, 2014 at 6:53 am - Reply

    I am so excited by the EBV hypothesis, thank you for this great article it gives so much hope that every possibility will be properly pursued in the quest to solve this awful disease.
    My medical knowledge is very sketchy to say the least but here are a few thoughts on other diseases that have been found to be caused by seemingly innocuous or common infections:
    The great flu epidemic after the end of the First World War was followed by an epidemic of sleeping sickness and in recent times the cause was discovered to be Streptococcus a common bacteria that usually lives harmlessly in the body. Hepatitis C, was another seemingly innocuous infection not taken seriously for decades, thought to be harmless but then discovered to cause liver failure 20-30 years after infection. The Polio virus is one of a family of enterovirouses that can live harmlessly in the body till triggered by some stressor and I’m sure there will be many other examples.
    It is so easy to take it for granted that common infections are all harmless, so I’m very grateful that all of these options are being explored.

  • Sheila

    May 14, 2014 at 4:47 pm - Reply

    The best treatment that I have ever heard of working was mentioned at hearings on the hill a few years ago. A doc from New York with CFIDS got Ozone IV infusions and it wiped out all the pathogens, be it viral or bacterial. It would be wonderful to be able to get some studies on this, however when drug companies cannot make outrageous amounts of money studies will not be done. I’m at the point that I will hunt down an ozone practioner here in Southeast Florida and try some infusions. At age 70 and suffering for over 31 years I feel I have nothing to lose at this time.

  • phillida bunkle

    June 3, 2014 at 9:58 am - Reply

    British Nutritionist, Anthony Hayes cleared chronic EVB in one of his patients over a period of 18 months by treating for alternating periods of 6 weeks with the natural antimicrobials ‘ADP’ made by American company Biotics Research and ‘Prolive’ made by American Company Allergy Resarch. These are available online in the United States and both are reputable companies.
    Slow but with the huge advantage of not disturbing gut flora and therefore risking exacerbating the autoimmune issues which seem to be central to CFS.
    Phillida

    • Sharon

      August 1, 2014 at 8:42 pm - Reply

      Did the individual recover? Do you know the exact antivirals used?

  • Marie

    June 16, 2014 at 7:45 am - Reply

    Would anyone else in this group have contracted the “Hong Kong Flu” of the 60′s? I was 5 or 6 years old. In a family of 7; I was the only person to have it. No sibling nor parent had any symptoms. I had a horrible experience. In later years I contracted Mono. This was at 13-14 years of age. It was after this that I was never the same. Tired all the time. Temperature sensitivities, I was always cold. I always felt sickly, went to the doctors a lot. I was often absent at school, could not participate in P.E. for most of the activities. I was just considered :lazy” and a hypochondriac. I suffered through having a 5 inch diameter cyst on an ovary, had my tonsils and adenoids removed. I went on my life, exhausted and feeling crappy, then married and had 3 children 2 years apart. I struggled bringing them up with my husband as I worked and cared for them. All three had serious health issues and I was on “Automatic” an energizer bunny exhausted. As they became older I began to become very ill. I had to stop working and am disabled now for 10 years. I have been diagnose with all the regulars, FM, CFS, Lupus, CRPS, CNS issues so bad that my large intestine became basically paralyzed and I ended up having to have it removed. Now being immobile I have lost much muscle mass. AND I have always had since I can remember “Chronic, Reactivated, Active EBV. Many strange lab results such as very high Eosinophil count. The worst symptom to me right now is that I fall asleep with no notice! I sleep about 18 hours a day. I have had sleep studies and everything…nothing wrong, no need for CPAP nothing I take large doses of Modafinal with my lARGE MIX OF MEDS AND STILL i STAY SLEEPING.There is so so much to list. I have not even gotten to bladder, and abdominal issues And of course the severe depression that comes with having a disease that no one knows what is wrong with you, It is almost unbearable! Pardon my long tirade, but I am desperate and am trying to come in contact with any sign of a “cure”. I pray that one will come quickly. I apologize for typos etc. falling asleep. Thank you for listening.

    • Cort Johnson

      June 16, 2014 at 3:58 pm - Reply

      I wish you the best of luck Marie. It’s hard for me, a laymen, to see how your issues aren’t viral related. Stay tuned on the Pridgen trial – may be after so many years there will be something for you.

      • Marie

        June 17, 2014 at 12:18 am - Reply

        Thank you Cort, I will think positive about these new findings!

    • OM

      June 16, 2014 at 6:07 pm - Reply

      Marie, have you had your thyroid: (Free T4, Free T3, Thyroid Antibodies TPO and Thyroglobulin) tested? Adrenals? Usually docs just do the TSH for thyroid testing but it is not enough and misses many people with thyroid hormone issues.

      • Sharon

        June 16, 2014 at 8:13 pm - Reply

        I didn’t get the Hong Kong Flu, but I did – foolishly – get the swine flu shot when the big scare came out about that. It was always in the back of my mind that maybe that played a part. I had mono as a teen & blood tests show high EBV levels.

        I have researched very hard trying to heal. A lot of research I’ve read up on lately is raising glutathione levels – shown to be low in fibro/ cfs. Glutathione is intricately related to your immune system, which fights off these viruses. Also, 70-80 % of your immune system is in the gut.

        You may want to trial some of what I am trying (believe me, I get very desperate also) – I started taking * Glutamine – which helps to boost glutathione as well as repairing leaky gut, and helping immune system. * NAC – hospitals actually use this to spike glutathione in cases of tylenol overdose * Liposomal glutathione (expensive/ tastes terrible, but other forms not well-absorbed) * Sulfur *High doses of powdered vitamin c (boosts glutathione)

        Someone also sent me a link where ProBost thymus extract helps the body to fight off toxins

        Please be forewarned that you may get a bad reaction to any of these.I got massive migraines when I tried glutamine before – and sulfur – and NAC. Now, I take a spoonful of glutamine right in my mouth & do okay.

        I get bad reactions to probiotics, but the immune system needs them, so I bought a sensitive brand ProBiota, and use Culterelle.

        I’m still struggling, but maybe something may help you.

      • Marie

        June 17, 2014 at 12:16 am - Reply

        To OM and Sharon,

        OM, thank you. Yes I have had my Thyroid checked and I am hypothyroid and I also have Hashimotos Thyroiditis. I have had polyps removed from my Thyroid which have been benign. I will have to check if adrenals have been checked. It seems I have had every test in the world since most occasions 11-13 tubes of blood are taken at a time.

        Sharon, thank you also. I am hesitant to try anything. I am on so many medications…Fentanyl Patch, Tramadol, Trazadone, Cymbalta, Modafinal, Neurontin, Diazapan, L-Thyroxine, Nexium and Naproxen EC, etc etc. So many medications to control pain, acid reflux, Unable to stay awake much so I take 400 mg Modafinal…still sleep so much.

        Thank you for trying

        • Sharon

          June 17, 2014 at 4:26 pm - Reply

          That could have been me writing that – I was on almost everything you named. The fentanyl slows your entire system down – as will the other meds. I think those things – while they served a purpose at the time – worsened my health by causing toxins to build up in my system.

          I am not medically trained, and don’t like to advise anyone else – just say what “I” am currently trying. One of the good things I did – finally – was to find a “higher-level” integrative doc. who didn’t just throw meds at me. I still feel like I’m mostly on my own, trying to fix myself, but a “good” dr. who works outside of the established methods of care, can help a lot more than you might think. I wish I hadn’t waited so long. Had a bad experience with one ‘holistic’ doc who ripped me off – but it’s like finding a needle in a haystack to find a really good doc. – I hope you find your way; good luck!

          • Marie

            June 18, 2014 at 5:46 pm -

            Sharon,
            Thank you for responding and letting me see a little possible lite in my future. How do you find a “higher-level” integrative doc? I have seen my current Internist for almost 26 years. He has been very supportive in trying to support me and refer me to specialist and he “believes” in me. However since the changes that have been made in the insurance industry he has changed. He has had to stop being the doctor that tries to help with research etc. He now, in accordance with our HMO, only treats colds etc. Anything else is sent to a “specialist”. And now if I ask a question about something that is happening he tells me it is not his specialty and has to refer me to one. Weird. I think he must have gotten in trouble at some point for making comments “out of his specialty” and was reprimanded. That is all I can think. Thank you Sharon!

  • OM

    June 17, 2014 at 7:21 pm - Reply

    Phillipa I am trying the Oregano/Olive leaf supplements you mentioned, why not? Marie, many people do better with natural thyroid hormone as it is more like what your body would make if it could. You can read a lot more about that at STTM Stop The Thyroid Madness website.

    • Marie

      June 18, 2014 at 5:21 pm - Reply

      Thank you OM. I will go to that site. I have heard some about natural thyroid hormone. I am wondering though, since I have Hashimotos Thyroiditis and most of my thyroid has been destroyed by it, if it would still help. I will read! Thank you for taking an interest!

      • phillida bunkle

        June 18, 2014 at 7:46 pm - Reply

        The women who got rid of chronic EB after a very long time took the oragano oil for six weeks followed by 6 weeks of Prolive an olive leaf extract made by US firm Allergy Research for six weeks and kept this up for a year and a half. She was then tested again for viral load and it had gone right down.
        I know this is a slow process but may be less harmful than some of the drastic things that have been done to you!
        The reason for switching around each 6 weeks was so that the bugs didnt develop immunity to either substance. SHE had NO side effects except getting much better.

        By the way I had a very bad bout of the Hong Kong flu in that outbreak in the 1950s and I was the only one in my family and it took me a very very long time to recover and later I developed CFS – from which I have now recovered.But if there is a type A flu around I tend to get it badly.

        Very very best wishes. go well

  • phillida bunkle

    June 18, 2014 at 7:53 pm - Reply

    hey but liposomal glutathione is heaps better. it is very hard to digest glutathione straight but the liposomal form is much better utalised. You may get a detox reaction at first so start very slow and feel your way up to a decent dose.

    I have had huge help from integrative doctors. You might look at the US based Institute of functional Medicine. They train doctors in nutrition and so forth and are mostly well meaning doctors of integrity.
    Best wishes,
    Phillida

    • Marie

      June 18, 2014 at 9:21 pm - Reply

      Thank you so much for sending me so much information. I finally find someone that was exposed to the Hong Kong Flu as well! I never was the same after that. Thank you all for this information. I will research it and put all info with my many many file folders of tests and results, I am going to look at the Institute of functional Medicine as well. Thank you all for caring. If you are suffering I feel for you, and I empathize. I am so weak but I can close my eyes and remember how to dance!

  • enya

    June 20, 2014 at 4:34 am - Reply

    Hi Cort,

    I am not sure if this came up before but don’t have the energy (ME) to study all files.

    What is your opinion or experience with Fecal Microbiotic Transplant.
    The list op options is getting smaller as my 20 year list of “try this and try that” has been getting longer.
    thanks a lot for feedback

    • Cort Johnson

      June 29, 2014 at 5:31 pm - Reply

      I’m looking forward to learning more about Fecal Transplants. I’m very encouraged by that possibility. I really want there to be more evidence of altered flora in ME/CFS and my guess is that we’re going to get that in the next couple of years. I’ll be doing a blog on fecal transplants at some point.

      • enya

        June 29, 2014 at 11:25 pm - Reply

        Hi Cort,
        After so many years and so many things I have tried I have taken the plunge and am self administering FMT at home by enema.
        My husband is my donor. I think I have nothing to lose and am very encouraged by what I have found out about it. I did not take special preparations to start. (like antibiotics)
        I did 6 days in a row then had a break of 2 days and again did 6 days in a row. Now I am doing every other day and will taper off.It had a lot of side effects(they call it die off) feverish, exhausted, nausea, extreme lightheaded. Now that is gone. I feel more alert and get some energy (not yet more then before I started) One interesting thing is that I was very addicted to cheese and could eat it ll day. I went to the fridge a lot. Since the FMT that urge is completely gone. I ate a cheese sandwich maybe twice and enjoy it, but there is no need for more. Let me know if you want me to keep you up to date and I will answer all your questions. If it can help you and other people I will be your guinea pig.

  • sue

    July 24, 2014 at 1:23 pm - Reply

    why don’t they just give rituximab and follow it up with Valtrex to make sure new B cells don’t get infected, and see what happens? maybe someone has done this already. might put the ebv issue to rest.

    • Cort Johnson

      July 31, 2014 at 4:44 pm - Reply

      Nice idea. Kogelnik is combining Rituximab with an antiviral in some patients. :)

      • sue

        July 31, 2014 at 4:50 pm - Reply

        Is it working?

        • Cort Johnson

          July 31, 2014 at 4:53 pm - Reply

          I have not idea. I know that some people on Rituximab alone have had really, really good results but I don’t know if its a few, a significant subset or what.

          • sue

            July 31, 2014 at 5:02 pm -

            but they go into remission only for a while…from a couple of months to maybe 2 yrs max, right?

  • Cort Johnson

    July 31, 2014 at 5:17 pm - Reply

    For those for whom it works my understanding is that they do.

  • Sharon

    August 1, 2014 at 8:39 pm - Reply

    Marie,

    “Higher Level Doc” was my own phrase – I meant a doctor who is trained medically, but also integratively – using holistic treatments. You can try the American College for Advancement in Medicine website – but remember – you are still taking a chance, because there are some greedy/ unqualified holistic docs as well. The other drawback is many don’t accept insurance. However, spending money on seeing a fibro specialist was, for me – money well spent.

    Cort:

    Since you are in the thick of things with research – isn’t there some compilation of people who have recovered from cfids/ fms – and which protocols they used? Dealing with these long-term health challenges has to be one of the most frustrating things on the planet. Following blind alleys and spending money on endless things purported to work. It’s maddening.

  • sue

    August 14, 2014 at 5:09 am - Reply

    if EBV was the culprit, wouldnt demeirlier/lombardi have found evidence of it in their study? they used actual tissue and next generation sequencing…albeit a small sample size…

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