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EBV I: A Deficient Immune Response, Increased Levels of Epstein-Barr Virus Opens Up EBV Question in Chronic Fatigue Syndrome Again

A Long History

Although altered EBV-specific antibody titers have been repeatedly demonstrated in CFS, no clear evidence for chronic EBV replication has been obtained so far. Authors

Perhaps the most common viral trigger for chronic fatigue syndrome (infectious mononucleosis, aka glandular fever) or Epstein Barr Virus (EBV) is a herpesvirus almost all adults have been exposed to and carry, usually in latent form in their cells.

conflicting signs

Conflicting results have made it difficult to determine the role EBV plays in ME/CFS. Will this German study signal a change?

EBV infection was proposed as the cause of chronic fatigue syndrome not long after the disorder became prominent in the 1980s, but inconsistent study results in the 1980s and 1990s followed by Straus’s 2000 paper (which suggested the search for herpesvirus infections in ME/CFS was over) put a damper on EBV research efforts.

From 2000 to the present only Dr. Lerner with his stream of positive studies (but sometimes challenging study designs) and Dr. Glaser published fairly consistently on EBV in ME/CFS. Recently Dr. Lipkin stated (unpublished) he found no evidence of active EBV infection using high throughput sequencing in the plasma of hundreds of ME/CFS patients.

Despite study inconsistencies, EBV has remained a pathogen of interest in ME/CFS. Both Lerner and Glaser have produced evidence suggesting that a defective form of the EBV virus may be causing the symptoms in some people with ME/CFS. Recent studies suggesting that EBV triggers autoimmune disorders are intriguing given the successful ME/CFS Rituximab treatment trials.

EBV’s ability to reactivate during stress and in hypoxic conditions may have implications for its possible role in ME/CFS as well. A recent laboratory study suggesting that high rates of oxidative stress can reactivate EBV and that antioxidants (including NAC, catalase, and L-glutathione) might be helpful in reducing EBV reactivation is intriguing given the high rates of oxidative stress found in ME/CFS.

Now, in a surprising turn, German researchers have not only put the spotlight back on EBV, but have dug deeper into EBV, ME/CFS, and the associated immune response than any group has before.

The Study

“Taken together, our study provides clear evidence that deficiency of EBV-specific immune response is present in CFS” The authors

The adaptive part of the immune system, the one that takes time to kick in, comes in the form of B-cell produced antibodies that lock onto proteins the virus produces and cytotoxic T-cells that attempt to the kill the virus. (B-cell’s attack the virus in the blood and cytotoxic T-cell attack virally infected cells.)

broken

Ohio State researchers believe a defective form of EBV that is spewing out proteins may be causing ME/CFS

Noting some unusual findings in their lab, these researchers looked at these antibodies and T-cells to see if people with chronic fatigue syndrome were mounting an effective immune response against EBV. They also looked for direct evidence of an active EBV infection.

EBV replication occurs when the virus produces proteins in a sequence that allows it to build another virus. One theory, developed by Dr. Lerner and a group at The Ohio State University (that includes Drs. Ariza, Glaser, and Williams), proposes that EBV undergoes ‘abortive replication’ in some people with ME/CFS. In abortive replication, a defective form of EBV produces early proteins, but is unable to produce later ones. The Ohio State group believes continual production of these proteins is causing a chronic inflammatory state in some people with ME/CFS.

Results

First, the German researchers found evidence of primary EBV infection or reactivation (increased IgM antibodies to a late EBV protein in @15% of patients vs 3% of controls) in significantly more ME/CFS patients than controls. The fact that this could be a ‘primary infection’; i.e. it represents the first time these patients are exposed to the virus is intriguing. A primary infection of EBV early in life usually leads to nothing more than a cold; a primary infection later in life can have serious consequences including infectious mononucleosis.

Having found evidence that an active EBV infection was more common in people with ME/CFS than controls, they looked to see if a reduced immune response was responsible for that.

The first hint of a reduced immune response to EBV in ME/CFS came in the form of a lack of antibodies to EBV-produced proteins VCA and EBNA1.

But first, a short antibody primer:

antibody

Antibodies attack pathogens in the blood; cytotoxic T-cells attack them in the cell

Antibody Types

  • IgG antibodies are ‘memory antibodies’ that travel through our system looking for evidence that a pathogen is present. Once your B-cells have mounted an attack against a pathogen, they are always present in our system. Therefore, IgG antibodies are not evidence of an ongoing infection.
  • IgM antibodies are attack proteins associated with a pathogen. High IgM titers to a viral protein generally reflect a primary infection.

With two types of antibodies being manufactured against a range of viral proteins the situation becomes complicated, but a healthy immune system should produce an array of both IgG and IgM antibodies that can detect (IgG) and inhibit (IgM) pathogens (found outside cells) at different stages of their lifecycles.

As they dug deeper, the German researchers found holes in the immune response to EBV in ME/CFS patients.

Immune Holes to Epstein-Barr Virus Found

Immune Hole #1 – reduced antibody response

Evidence of a impaired B-cell response to EBV first came in the form of missing IgG antibodies to VCA and EBNA in 13% of ME/CFS patients compared to 4% of controls. This indicated that 13% of their ME/CFS study population did not have some of the memory B-cells needed to detect an EBV infection.

Increased IgM antibody responses in ME/CFS (17.5% in ME/CFS vs 4% in controls), on the other hand, suggested active and perhaps primary EBV infections were more commonly found in ME/CFS patients.

All told, 30% of the ME/CFS patients either had reduced IgG (EBNA-IgG) or increased IgM (VCA) responses to EBV.

That finding prompted a deeper look, and a much larger study that found no IgG response to a protein expressed during latency by EBV (called EBNA-1 protein) in 10% of IgG positive ME/CS patients. This indicated that the immune systems of approximately 10% of the ME/CFS group were unable to detect a very early stage of EBV latency.

EBV

The EBNA-1 protein featured in many of the tests helps EBV maintain its latency in B-cells

Latency – For EBV to maintain itself in the body over time, it needs to be able to maintain itself in B-cells in a process called latency. EBNA-1 is a protein that helps maintain EBV’s viral genome in the earliest stages of latency.

The authors noted that people with severe infectious mononucleosis and chronic active Epstein-Barr virus disease have similar findings (although it’s not clear why, given that EBNA-1 is not involved, so far as we know, in replication).

That brings up the question of how many people with ME/CFS would have fit into the category of severe mononucleosis at the time they got ill. The Dubbo studies found that more severe infections greatly increase the risk of coming down with ME/CFS.

Immune Hole #2 – reduced frequencies of two B-cell antibody producing cells

Intrigued by the findings, the German researchers dug deeper into the immune response to EBV. They took blood (PBMCs) from ME/CFS patients and then stimulated it with CpG, SAC, and PWM for seven days, and found reduced frequencies of B-cells producing antibodies against VCA and EBNA-1, and for the first time they found evidence of immune deficiencies in most people with ME/CFS.

No less than 59% of ME/CFS samples had a diminished response to a later stage EBV protein (VCA) produced during the late stage of lytic replication, and a whopping 76% of ME/CFS samples had a diminished response to the EBNA-1 protein. With the VCA finding we have evidence suggesting many people with ME/CFS may have trouble controlling EBV replication.

Calling the findings ‘remarkable’, the authors suggested that either the memory B-cells associated with these EBV antigens had been lost or had failed to develop into antibody-secreting cells.

Immune Hole #3 – Reduced T-cell response to EBNA-1

A similar deficiency in the T-cell response to EBNA-1 indicated that both arms of the adaptive immune response to Epstein-Barr Virus, the B-cells and the T-cells, had difficult recognizing and responding to this protein.

Citing other disorders such as HIV, they suggested that persistent EBV reactivation in ME/CFS had driven the T-cell response in ME/CFS into ‘exhaustion’. (A similar suggestion has been made with regard to natural killer cells that attack pathogens early in an infection, which use killing methods similar to those employed by T-cells.)

Further analysis suggested that T-cell suppressor cells which decrease B-cell responses were not responsible for the B-cell suppression found. Normal B-cell responses to herpes simplex and cytomegalovirus suggested that the deficient B-cell responses were associated with EBV and not other herpesviruses.

cytotoxic T-cell

Lower cytotoxic T-cell responses to EBNA-1 could be associated with an increased risk of autoimmune disorders

Immune Hole #4 – reduced T-cell response to EBNA-1, reduced T-cell responses to EBV

Next they explored T-cell induced cytokine production. The T-cells should produce an array of cytokines against EBV. About 20% fewer ME/CFS patients (70% of controls vs 50% of ME/CFS patients) were able to mount an IFN-y response against EBV.

Looking specifically at the latency associated EBNA-I protein, they found the startling result that no ME/CFS patients mounted an IFN-y response against it.

They also found that ME/CFS patients produced significantly lower amounts of the pro-inflammatory cytokine TNF-a in response to EBV. Finally, a lower percentage of patients produced IL-2 as well. The reduced cytokine production suggested cytotoxic T-cells, one of the big guns of the adaptive immune response, were not being strongly activated in response to EBV.

Immune Hole #5 – Reduced frequencies of EBNA-1 specific T-cells

The researchers dug deeper still. Next they stimulated the blood (PBMCs) of ME/CFS patients and healthy controls (n=40) with the EBNA-1 protein, expanded the cells in the presence of IL-2 and Il-7, and then checked the T-cell response to them. Specific types of T-cells should be produced to attack EBV, but reduced frequencies of EBV-specific T-cells occurred in about 50% of the ME/CFS samples. That again suggested the cytotoxic T-cell response to the EBNA-1 protein was substantially reduced in ME/CFS.

Direct Evidence of Active EBV Infection

“Remarkably, in line with this finding we could provide evidence of enhanced viral load of EBV by detection of EBV DNA in a significantly higher proportion of patients compared to healthy controls.” The authors

Using a real-time PCR test in the whole blood that looked for ‘low-copy’ numbers (<1,000-2930 copies/ml) they found evidence of increased EBV viral load in 7.2% of 290 ME/CFS patients. When they dug deeper and did the same test in PBMCs in a subset of patients, they found that a whopping 55% of patients (vs 13% of controls) tested positive for EBV.

The viral loads were far below those found in other EBV associated illnesses such as infectious mononucleosis or post-transplant EBV infections, and there was no evidence of lytic replication (i.e., full replication of the virus), but something the authors called ‘latency-associated replication’ was common in people with ME/CFS, yet not in healthy controls.

The Lipkin Study

Using PCR the German researchers found much higher rates of EBV infection in PBMCs vs whole blood and no evidence of EBV infection in plasma.

plasma-blood

Was looking for EBV in plasma somehow a mistake?

Neither the Lipkin CFI ME/CFS pathogen study nor the CFIDS Association of America BSR study found evidence of EBV infection in ME/CFS. According to Russell Fleming’s transcript of the Lipkin talk, the CFI study looked in the plasma of both the Montoya and the ME/CFS experts’ samples.

Whole blood contains plasma, red blood cells, white blood cells, and platelets. Plasma makes up 55% of blood volume and contains water (90%), proteins, nutrients, waste products, clotting factors, hormones and carbon dioxide. It does not contain red or white blood cells or thrombocytes.

EBV DNA has certainly been found successfully in plasma before and plasma has been used to track EBV activation. Serum/plasma EBV PCR kits are available for purchase. Researchers search and find EBV in plasma frequently.

Dr. Chia, however, reportedly stated he believes the use of plasma rather than blood was a serious mistake, and the Germans were able to find evidence of EBV activation in blood but not in plasma.

EBV (and CMV and HHV-6) are ‘cell-associated viruses. The only times their DNA escapes the cells is when the cell dies (and the DNA goes into the plasma) or when the virus is replicating. Otherwise the virus sits in a latent or semi-latent state in the cells
Medical dogma states if you can’t find EBV in the plasma, the infection is not active. EBV DNA can be found in the plasma when EBV replication rates are high, as sometimes occurs in transplant patients, but it’s not likely to be found in the smoldering infection believed present in ME/CFS. Many researchers do not accept the idea of a smoldering infection that pumps out proteins which trigger an inflammatory response.

The German researchers are deepening their study of EBV and ME/CFS and currently evaluating antibody responses against a broader variety of EBV peptides derived from 8 different proteins. They are also quantifying the levels of memory B-cells targeting EBNA-1 and VCA.

Conclusion

“We think the altered pattern of the specific immune response to EBV may be suitable as a diagnostic marker for CFS.” Authors

ball of string

The harder they looked, the more they found …

It was if these researchers kept pulling a string that got longer and longer. First their interest was piqued by some paradoxical antibody findings, then they found widespread deficiencies in some antibody responses and T-cell responses, and finally they saw evidence of an active EBV infection in the blood of 55% people with ME/CFS (vs 7% of controls).

Much is still unclear. The EBNA-1 protein that the immune systems of ME/CFS patients had trouble responding to is associated with ‘early latency’, not EBV replication. The authors’ reference to ‘latency associated replication’ is unclear given that latency is not usually associated with replication. When asked what importance their findings have for EBV reactivation or EBV survival or  more severe casesof infectious mononucleosis in ME/CFS, the authors stated they can’t answer those questions yet.

Some researchers believe, however, that reduced cytotoxic T-cell responses to EBV increase the risk for autoimmune disorders. (We’ll be covering that possibility in the next blog.) These findings also suggest that the proposal by Lerner and the OSU group of Drs. Ariza, Glazer, and Williams that an abortive lytic process (smoldering EBV infection) is present in many people with ME/CFS may be correct.

While it will take more work to determine what these findings mean for ME/CFS,  the broad range of dysfunction  found and the high rate of active EBV infection (in plasma) would appear to put this pathogen back into play in a meaningful way in ME/CFS.

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43 Comments

  • Sam Glickman

    March 13, 2014 at 5:37 pm - Reply

    @Guido den Broeder: You can find the original study here: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0085387

  • barrie

    March 13, 2014 at 5:57 pm - Reply

    Thank you for this article. Please, would it be possible for articles to feature a summary box for those of PWME like me who are to ill to read and comprehend a complete article. Thank you!

    • Cort Johnson

      March 13, 2014 at 6:26 pm - Reply

      Good idea. Probably the best place to look right now is the conclusions.

  • Johannes Starke

    March 13, 2014 at 8:06 pm - Reply

    A study is a great example that we, the me/cfs community, can rejoice in the progress that is made in areas of research unrelated to ME/CFS.

    I bet a lot of money and time went into developing the tests that these researchers were able to adapt with relatively little effort to their ME/CFS research.

    Likewise, the XMRV findings used knowhow that was developed with the millions of dollars that go into cancer research.

    Unfortunately, right now the research budget is even too small to translate breakthroughs from other areas into breakthroughs in ME/CFS.

    Still,, it gives me great hope that when we are able to come up with a decent research budget ourselves, we won’t have to reinvent the wheel, but can instead build on the progress made in other areas of medical research.

  • Claudia Heath

    March 13, 2014 at 9:26 pm - Reply

    I may have read over the numbers, but what was the size of the study?

    • Cort Johnson

      March 13, 2014 at 10:03 pm - Reply

      I didn’t put them in. It was thankfully a very big study with about 60 people in the first part and over 300 in the second. Some of the tests were run on cohorts with about 20-30 people in them.

      • Claudia Heath

        March 13, 2014 at 10:53 pm - Reply

        Thanks, Cort. I intend to run this study by our ME specialist, who authored the Dubbo study. It takes a lot to satisfy his high standards, sobbI want to be prepared.

        • Cort Johnson

          March 13, 2014 at 10:57 pm - Reply

          If that’s Andrew Lloyd I’d love to hear what he has to say. He does have very high standards. I remember him telling a conference full of researchers that they were pretty much full of it on one topic. Sometimes he’s right! :)

          • Claudia Heath

            March 13, 2014 at 11:19 pm -

            The very same. The response you heard is typical. I am scientifically useless but I can at least hear his opinion. Next appointment is beginning of May so I’ll feed back to you then. He is just pubishing results of his own longitudinal research from the NSW Uni Lifestyle Clinic Fatigue Program so that will be of interest to discuss, too.

  • Ann

    March 13, 2014 at 9:48 pm - Reply

    Thank you Cort for this very encouraging article. It gives me hope that the future for ME patients is much brighter after reading about new directions with EBV research.

    • Cort Johnson

      March 13, 2014 at 10:07 pm - Reply

      It kind of came out of the blue didn’t it? It just shows you never know. :)

  • K. Brown

    March 13, 2014 at 9:50 pm - Reply

    I can’t describe how excited this makes me. I read Dr. Lerner’s research as far back as 2008 and thought his theory was quite possible. He also was one of the first I’d known of to give Valcyte or Valtrex and at that time he had a better rate of cure or vast improvement of his study patients than anyone. I believe his work was the basis of Dr. Montoya and Koeglenik’s work which also helped many in their small studies. I hope they have or get the money they need to continue this most exciting research. I want to send them flowers or something. Wow, this seems to be giant news in my opinion. I wondered if getting blood transfusions of someone who had the proper immune responses to EBV could alleviate the symptoms of those of us with ME/CFS. Can’t wait til they find out more.

    • Cort Johnson

      March 13, 2014 at 10:06 pm - Reply

      I talked to researchers associated with Dr. Lerner at Ohio State University. They did not agree with all the interpretations (latency associated replication) but they did feel the finding fit with Lerner’s hypothesis.

      I think it’s pretty darn big news; nobody has looked at EBV like this before in ME/CFS. The German researchers are going to dig deeper. It’s going to be very interesting and hopefully this research will spark more research in the US. I’m going to try to snag Montoya and others and ask them about this paper and Symposium and conference.

      • K. Brown

        March 13, 2014 at 10:21 pm - Reply

        I don’t see how these findings couldn’t be big news. Hopefully this doesn’t slam into the ground the way XMRV did. If our genetics are what cause the inability of the immune system to fully squash an EBV infection I wonder what the treatment or cure might be for that. I know, it’s too soon to be getting that hopeful, but I just can’t help it. When was there anything this explicit in the bloodwork of ME/CFS?

  • Kristina

    March 13, 2014 at 10:45 pm - Reply

    Thanks Cort, that’s fantastic!

  • Kathy

    March 13, 2014 at 11:35 pm - Reply

    In my early days after diagnosis, 33 years ago, my blood tests showed suspicious ebv activity and considering I’d had a particularly severe case of mono at age 13 I’ve always presumed ebv and me/cfs are related. Though at the time ebv was a topic of conversation in the community it wasn’t given any legitimacy by the medical/research fields. Probably another case of valuable time being lost in the quest to understand/cure this illness being strangled in its infancy since after all it only affected over achieving ‘yuppies’ -/ sarcasm off.

    • Cort Johnson

      March 14, 2014 at 5:24 pm - Reply

      Be sure to read the next blog – it’s a real eye opener.

  • Marg

    March 14, 2014 at 12:18 am - Reply

    Thanks Cort, this article was amazing. It sounds just like my first visit with Dr. Klimas and her explaining all and the how the whole thing was suppose to work but it was not.. My EVB titers were very high and the T and B cells not very good. My immune system was broken!

    Kathy you and I got sick at about the same time and the first doctors I went to would not even test for EVB, too controversial so they said and everyone had it over 30. Years wasted…I did with a lot of work on my part and a naturopath have and 8 year remission but it came back 5 years ago. I am doing well with Imunovir but have started having trouble with Acyclovir. I was told a side effect is uric acid and I will be tested when the papers arrive. I think that is it…burning pain and when I stop it goes f down 77%. I started and stopped 3 times and the same response… Here is to the “Yuppi “Flu!

  • Chris

    March 14, 2014 at 1:23 am - Reply

    I’m thinking of Erik who did not have the EBV titer response that others showed, yet he was pretty much as sick as everyone else before he got out of Dodge and began avoiding what some believe are mold toxins. Granted, Glaser et. al. and the Germans are now looking at new parameters; I wonder if EBV is really the primary trigger or just another degree of disruption with its own consequences that he hadn’t reached yet, maybe. I wish there was a way to go back in time an look anew. Treating the herpes infection works for some; so many chicken-and-egg questions.

  • Eilidh Hewitt

    March 14, 2014 at 10:08 am - Reply

    EBV makes such sense; could it be that the cause of ME has been hidden in plain sight all along, something so obvious it has just been ignored? Often the solution to a problem is beautiful in its simplicity even though the initial problem seems so complex.

    So many cases of ME are triggered by Glandular Fever and the time lag of a latent infection could account for the others. It could be behaving like Hepatitis C or as Polio did in the past. Glandular Fever has a reputation for incomplete recovery and for recurring. In sport they know about its potentially destructive nature and athletes can be advised to take a year off to rest and recover. Glandular Fever can be a very nasty infection indeed and the possibility of long term complications seems to be hugely underestimated.

    I think the most significant recurring symptoms in ME are; sore throat and painful swollen glands in the neck and arm pits with bodily aches and mild fever. I have often thought that these symptoms must be a sign of persistent infection.

    There are many accounts of people having recurring symptoms years after infection. Surely we have been missing something in not considering Glandular Fever as the culprit when this infection behaves in a way that is so like ME itself. It’s perfectly logical to think it could cause ME. This is an interesting paper about a link between Glandular Fever and developing MS. http://www.independent.co.uk/life-style/health-and-families/health-news/childhood-glandular-fever-linked-to-multiple-sclerosis-6170950.html

    Its 25 years since myself and three of my children, fell ill with Severe ME after Glandular Fever. In all these years I have never heard of anything that has had more potential as a possible cause for ME as EBV and Glandular Fever and I imagine the Vagus Nerve Hypothesis would fit in with it.

    17 years after developing ME my three children went on to develop other serious disease. One has Gastroparesis (paralysis of the stomach) a connection here with the Vagus Nerve as it controls the stomach. Another has developed MS and Ulcerative Colitis and the third Coeliac disease and Keratoconus (eye disease of the corneas). My niece also became ill with ME after Glandular Fever and she went on years later to develop intractable Inter-cranial Hypertension that has to be controlled by shunts.

    NHS Choices; “Someone with Glandular Fever is contagious for at least two months after initially being infected with EBV. However, some people can have EBV in their saliva for up to 18 months after having the infection. A few may continue to have the virus in their saliva on and off for years”.

    Wikipedia; “fatigue and a general feeling of being unwell may sometimes last for months.[6] Fatigue lasts more than one month in an estimated 9–22% of cases.[3] In cases where fatigue lingers, it generally passes spontaneously within 2 years.[3] Mild fever, swollen neck glands and body aches may also persist beyond 4 weeks.[6][9][10] “

    • Cort Johnson

      March 14, 2014 at 5:23 pm - Reply

      Your family has really been through it! Be sure to check out the next blog; it’s will be a real eye-opener. How old were your children when they got glandular fever?

      • Eilidh Hewitt

        March 15, 2014 at 8:20 am - Reply

        Thank you Cort you have done a very fine job on this EBV Glandular fever article and I will certinly be looking out for the next one.

        To answer your question; This is something that puzzles me because my children were young when infected with Glandular Fever but had a disasterous outcome. Two had Glandular fever at 10 and 11 years of age and the the other, who now has MS and Ulcerative Colitis, was 6, tested positive at the time. The MS paper link I included fits with his experience. We have heard of other severe childhood sufferers who have had the same experience of developing other conditions just as they were recovering.

        • Ann

          March 15, 2014 at 8:37 am - Reply

          Dear Eilidh

          How brave you are.

          After reading your concise, informative and very moving account of your family’s illnesses, I can only hope that it has given you a small amount of relief, to let others know the exact realitiy of suffering from ME.

          With so many conditions relating to ME, your story shows the stark, unstripped version of life with this illness and I would imagine many people reading this will have their eyes opened wide. The very nature of the illnesses, within your family alone, cannot help but move the most sceptical mind.

          You will always be my source of inspiration and my guidance through this terrible disease.

          You are the true angels of this world and I pray that EBV is found to be the answer to all our prayers, with a cure to follow.

          Cort, This lady has been our bible, here in this part of the UK and when she speaks, I know it’s important to listen. Thank you Eilidh and thank you Cort for allowing this forum.

          I’m pleased to say Eilidhis a true friend and honoured to know her and her family.

          Lots of love
          Ann O’Connellxx

          • Eilidh Hewitt

            March 15, 2014 at 2:03 pm -

            Thank you Ann
            For your support and very kind words. Especially poignant knowing your history, how ill you are yourself with ME and also how you have other family members affected as well.
            It’s always an honour and a great help to share times of trial with good friends, people that understand each other and the awful hardships and feats of endurance forced on us, that inevitably come with ME.
            Love and best wishes to you and your family
            Eilidhxx

  • Simon McGrath

    March 14, 2014 at 3:24 pm - Reply

    Thanks, Cort, that was one of your very finest.

    • Cort Johnson

      March 14, 2014 at 5:17 pm - Reply

      Thanks, Simon – EBV is really complex and I had some help. My first draft was full of errors actually (lol)

      • Simon McGrath

        March 15, 2014 at 11:18 pm - Reply

        Still impressed – I tried to read the paper and had to give up on it!

  • Jean

    March 14, 2014 at 3:26 pm - Reply

    I was very ill in 1993 (Fall)
    Diagnosed of FMS 1994 at a Boston Hospital, have tried my best to live with it, although it is not the living I once had.
    I found this article very interesting, as my partner (retired psychiatrist) , came down with EBV, / Mono age 50, after which he never fully recovered, and was told he had FBS.
    We both also have extensive OA, I am 56 and he is 62, is there any connection???
    Please, and Thank-you.

    • Cort Johnson

      March 14, 2014 at 5:21 pm - Reply

      What I am learning about EBV is that if you have a primary infection at any other time than childhood you could be in trouble. A primary infection (i.e. the first time you’re exposed) in adolescence may very well end up in a case of infectious mononucleosis – which greatly increases your risk of coming down with ME/CFS or multiple sclerosis. If your partner’s primary infection was at age 50, his immune system probably wasn’t able to deal with it. Our immune systems as infants are actually far stronger than they are as adults.

      Infants usually have no problems with EBV; in fact, they don’t even notice it – their immune systems quickly take care of it.

      The next blog is going to focus on EBV and autoimmunity – be sure to check it out.

      • Jean

        March 16, 2014 at 7:10 pm - Reply

        Thank you for your answer and the research you are doing Dr. Johnson. Very much appreciated.

  • Mike

    March 15, 2014 at 9:04 pm - Reply

    “When they dug deeper and did the same test in PBMCs in a subset of patients, they found that a whopping 55% of patients (vs 13% of controls) tested positive for EBV.”

    Why did they run PCR testing on PBMCs only in a SUBSET of patients, as opposed to the entire study sample? How did they select which patient samples would be included in the subset? Were they selected based on other characteristics that the researchers thought made it more likely that an EBV infection would be found? Or was it done randomly for practical/logistic reasons (e.g., it was too expensive to do this for the entire study sample)?

    In other words, does the research imply that roughly 55% of ALL CFS patients could have EBV infection in their PBMCs? Or does it merely imply a 55% infection rate in a particluar SUBSET of CFS patients with characteristics distinguishing them from other CFS patients?

    • Mike

      March 15, 2014 at 9:06 pm - Reply

      And by “particluar,” I meant “particular…”

  • Ann

    March 16, 2014 at 3:15 pm - Reply

    In response to the ages of Eilidh’s children developing serious diseases and them testing positive for Glandular fever at as young, in one case ,as 6 years of age, could this be part of the latency/contributing factorsargument, rather than late infection with EBV, causing serious disease? That is, if late teens develop EBV/glandular Fever, is it more likely that they are subjects of latency and reactivation from a childhood infection with EBV?

    If children have EBV infection, but don’t go on to develop diseases, perhaps it could lie dormant until the reactivation is caused by other factors, in some cases, rather than the primary disease infecting at that later age. Teenagers are routinely checked for Glandualr Fever due to its prevalence at that age, where as I’m not sure children would be.

    EBV also causes many cancers (ME Research UK). In particular Lymphomas, which can affect ME sufferers. Could connections be made here I wonder?

    Ann OConnell

  • Jacque

    March 20, 2014 at 1:18 am - Reply

    Sure rings true to me… My EBV and HHV6…HSV! and 1 titres are through the roof…and NK Cells in the toilet…. I found the hypoxic comment interesting..as I cannot fly if I EVER do get to travel or I get terribly ill.. I also get terribly ill in high altitudes!! Very interesting…. Thank you for all you do to keep us informed Cort…. Why does this have to be soooo complicated? I read every article with tears of pain and frustration streaming down my cheeks. My son who is 24 has MANY of the mysterious symptoms and I am just sickened even more to know this may be his life too… I hope not…I hope they get a handle on this soon…before half of our nation are “hypochondriacs who can’t go to work”!:(

    • Cort Johnson

      April 14, 2014 at 7:21 pm - Reply

      I think we’re getting closer and yes, it is very complicated isn’t it? But that’s one reason ME/CFS is still such a mystery; it doesn’t fit into the usual boxes. Good luck with your son :)

  • Linda

    April 7, 2014 at 4:15 pm - Reply

    My practitioner is currently helping remove EPV from my body with Chuan Xin Lian ( which i believe is Andographis) Huang Lian joe Du Wan and Lauricidin. This has been a big co-infection for me while fighting Lyme disease.

  • carlie

    April 27, 2014 at 6:44 am - Reply

    I currently have chronic ebv and was wondering if any of you have tried lauricidin? I also have problems with my family who tell me this is not a real disease or just doesnt exist. Its so hard to deal.

    • K. Brown

      April 27, 2014 at 5:19 pm - Reply

      My bloodwork showed high titres of antibodies to EBV and this article explains why that is probably so. My immune system can keep it from being a full blown infection, but it can’t rid itself of some of the effects – if I understand correctly. I have so many symptoms its hard to ever know what causes any of them. If by lauricidin you mean monolaurin or lauric acid, I have recently begun to take it to see if it would have any effect on any of my symptoms. The one I KNOW it has helped in a profound way was the burning tongue I had. Almost anything I eat or drink caused my tongue to burn, it didn’t look red at all but inside if always felt like I had been drinking boiling hot coffee. I take 3-4 1,100mg capsules a day of monolaurin from coconut and now my tongue barely ever has a feeling of burning in it. If I quit taking them or miss one I can tell it’s still a problem, but as long as I’m taking at least 3 a day I am seldom aware of any burning sensation. Cytomegalovirus is one virus that lives in the tongue, I’m sure there are others, but my bloodwork also showed a high IGg level so I think maybe that is what the monolaurin works on – all supposition on my part, but it does help that. I hope if I stay on it I may find it helps other things as well over time. Supposedly kills “enveloped” viruses because it destroys the envelope of those viruses which kills them. The world of viruses is vast and complex. As for your family, I’m sure most of us can identify with that problem. The thing is, now there is enough medical proof of all the problems with so many systems in our bodies.
      The brain, sinuses, throats, hearts, lungs, stomach, nervous system. If they still don’t believe after reading the latest evidence from researchers all over the world then they probably also think the sun revolves around the earth.

  • carlie

    April 27, 2014 at 6:46 am - Reply

    oh wait I see Linda is trying this. I cant wait until it arrives, I also wondered about olive leaf extract.

  • Cassandra

    May 21, 2014 at 7:20 pm - Reply

    It took my doctor forever to figure out I even had EBV, because I didn’t have most of the usual symptoms – no sore throat, no elevated white blood cell count, no fever. I just felt awful. The only thing that tipped him off was that a CT scan showed some “lesions” on my spleen, and that led him to test specifically for EBV. The only explanation he could give was that some people’s immune systems just don’t respond to the virus the way they’re supposed to. Two years later I still haven’t fully recovered, and they’re calling it CFS. Interesting to see that there are other people following similar patterns.

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