• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Positive EBV VCA-IgM for at least six months. false positive?

Messages
87
Tested in July, August, and December, tests for EBV were consistently the same:
VCA IgG Negative
VCA IgM Positive
EA Negative
NA Negative.

At first glance, this appears to be the acute phase of a new EBV infection, however, a retest in December doesn't show the progression of the infection and the initial test doesn't match the timeline for onset of symptoms.

I think I've never had EBV virus and the EBV VCA-IgM is a false positive. I think that if this was a real infection, we would see all of the antibodies by December. Is this a false positive, or is it the smoking gun?

This is a chart for the interpretation of EBV derived from the normal progression of the virus.
F1.large.jpg


Pictured results were run at Cleveland Clinic internal lab. Cleveland Clinic lab appears to normalize the results and then lists interpretation as follows:

EBV VCA IgG
AI VALUES ARE INTERPRETED AS FOLLOWS:
NEGATIVE SPECIMENS <=0.8
EQUIVOCAL SPECIMENS 0.9 TO 1.0
POSITIVE SPECIMENS >=1.1

EBV VCA,
AI VALUES ARE INTERPRETED AS FOLLOWS:
NEGATIVE SPECIMENS <=0.8
EQUIVOCAL SPECIMENS 0.9 TO 1.0
POSITIVE SPECIMENS >=1.1

EBV EA
AI VALUES ARE INTERPRETED AS FOLLOWS:
NEGATIVE SPECIMENS <=0.8
EQUIVOCAL SPECIMENS 0.9 TO 1.0
POSITIVE SPECIMENS >=1.1

EBV NA
AI VALUES ARE INTERPRETED AS FOLLOWS:
NEGATIVE SPECIMENS <=0.8
EQUIVOCAL SPECIMENS 0.9 TO 1.0
POSITIVE SPECIMENS >=1.1
 

Attachments

  • ebv.PNG
    ebv.PNG
    19.2 KB · Views: 61

rodgergrummidge

Senior Member
Messages
124
Hi @.jm.

As you show in your diagram, VCA IgM is usually diagnostic for acute infection and usually appears prior to VCA IgG. In your case, you have an unexpected serology profile in which VCA IgM is positive for a prolonged period of time (6 months) while the expected development of VCA, EA and EBNA antibodies have not been detected.

The panel of VCA IgG, EA IgG, EBNA IgG and VCA IgM can successfully diagnose i) EBV naive ii) acute EBV infection, iii) past EBV infection greater than 95% of the time (NEJM, 343: 481). Thus, you are probably in the ~5% of patients having a non-specific cross reaction in the serology test where the results are not internally consistent with how acute EBV infection is known to progress.

In your case, there are several likely possibilities.
  • If you were severely ill, immunocompromized and had a chronic active EBV infection, your serology profile might make sense. Chronic active EBV infection is a serious medical condition distinct from CFS and consists of chronic or intermittent fever, lymphoproliferation (or lymphocytosis), hepatosplenomegaly, persistent hepatitis and extensive lymphadenopathy. Patients with chronic active EBV have high viral loads in their peripheral blood and sometimes have unusual EBV serology profiles. Chronic EBV is rare but severe and patients have poor prognosis with high morbidity and mortality. If you had chronic active EBV, you would require immediate medical intervention (note the term chronic active EBV infection is not to be confused with 'latent infections' or such terms as 'low level infections' which are entirely different).
  • That the VCA IgM is a non-specific false-positive in the serology test.
  • You have an abnormal lymphocyte clone (in this case, lymphocyte clone is a population of identical lymphocytes) that is producing the VCA IgM antibodies. Such an abnormal lymphocyte clone might be dividing in an uncontrolled manner and as the clonal population increases, so does the VCA IgM production.
If you wanted a more definitive diagnosis, you could
  • get EBV PCR done on a throat swab, whole blood and plasma to determine if you have EBV virus present. If you are EBV PCR negative then you can confirm that your positive VCA IgM is actually a false positive.
  • tested for heterophile antibodies which are antibodies that agglutinate cells of other animal species. Heterophile antibodies are mainly associated with active infectious mononucleosis due to EBV. If you were negative for the heterophile test, then again, you can likely conclude that the VCA IgM result is a false positive.
  • see an immunologist and investigate your lymphocyte populations to determine if there might be an increased clonal population that is producing VCA IgM antibodies.
Non-specific positive results can sometimes occur in EBV serology. False positives are known to arise from interfering rheumatoid factor, autoantibodies, or cross-reacting factors such as hCMV or
parvovirus B19 (NEJM, 343: 481). So, if you have CFS or some other underlying medical condition, additional tests for rheumatoid factor, parvo B19 or autoantibodies might be warranted.

Rodger
 
Messages
87
I have something that is a mild chronic sore throat (I remembering it cycling though periods of being mildly sore almost continuously since at least October. I wrote it off as the listed side effect of one of the sleep drugs But possibly it belongs on my symptoms list).

I think your idea of a EBV PCR test to test for the present or absence of EBV is good. Absence will close this virus in the diagnostic process. Presence may suggest Dr. Martin Lerner's theory of aborted EBV infection. (notice that the IgG is low and "negative" but it isn't zero like EA/NA)

I've been tested for rheumatoid factor, and ANA. I assume there isn't any need to retest. But tests for hCMV and parvovirus B19 are warranted. There is also a recent paper (n=2 not that scientific, but interesting) that documents false positive results for EBV VCA IgM from Lyme disease.
 

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
I think your idea of a EBV PCR test to test for the present or absence of EBV is good.

Hey @.jm. -

Robert Naviaux is a virologist and a leading CFS researcher. This is a quote from him-

latent and reactivated viral and bacterial infections can occur, but in the case of ME/CFS that has lasted for more than 6 months, this may be the exception rather than the rule.

Some doctors and scientists have not done a good job at educating patients and other scientists about the difference between serological evidence of infection in the form of antibodies like IgM and IgG, and physical evidence of viral replication like PCR amplification of viral RNA or DNA, or bacterial DNA.

We have learned in our autism studies with Dr. Judy Van de Water that supertiters of antibodies do not mean new or reactivated viral replication. Supertiters of IgG antibodies mean that the balancing T-cell and NK cell mediated immune activity is decreased.

This is a functional kind of immune deficiency that causes an unbalanced increase in antibodies.
https://www.omf.ngo/2016/09/09/upda...-fatigue-syndrome-q-a-with-robert-naviaux-md/
https://www.omf.ngo/2016/09/09/upda...-fatigue-syndrome-q-a-with-robert-naviaux-md/
Jim
 

Hip

Senior Member
Messages
17,820
We have learned in our autism studies with Dr. Judy Van de Water that supertiters of antibodies do not mean new or reactivated viral replication. Supertiters of IgG antibodies mean that the balancing T-cell and NK cell mediated immune activity is decreased.

The meaning of the elevated viral antibody titers found in ME/CFS has always been an unresolved issue. One view, the one Naviaux seems to subscribe to, is that these high antibody titers are merely a dysfunction of the immune system, and that there is no actual ongoing infection.

But the other view, the view that tends to be held by the renowned ME/CFS clinicians, is that the high titers are the result of an ongoing infection, and that patients can improve when given antivirals.

Dr Martin Lerner's proposal was that in ME/CFS, there can be chronic active herpesvirus infections, but he believed these are not like regular chronic infections, but are abortive infections. Abortive infections can be ongoing chronic infections, but which rather unusually do not produce any new viral particles.

There is not much evidence for this abortive infection theory of ME/CFS at present, but if this theory is true, it may explain why testing for chronic infection in ME/CFS requires a different interpretation of the viral test results, compared to regular chronic active infections.

Dr Lerner says ME/CFS patients have an active EBV infection (which he believes is an abortive infection) when there are elevated antibodies in the EBV IgM VCA test and/or the EBV EA diffuse test. Ref: 1 2

So if you have elevated EBV IgM VCA, I think Dr Lerner would classify you as having an active EBV infection.

Info on Dr Lerner's treatment protocols given here.

Info on Dr Lerner's abortive herpesvirus infection theory of ME/CFS here.



I think I've never had EBV virus

EBV is found in 90% of adults, so it is common. You don't have to have mononucleosis to acquire EBV.
 

rodgergrummidge

Senior Member
Messages
124
Presence may suggest Dr. Martin Lerner's theory of aborted EBV infection.

Dr Martin Lerner's proposal was that in ME/CFS, there can be chronic active herpesvirus infections, but he believed these are not like regular chronic infections, but are abortive infections. Abortive infections can be ongoing chronic infections, but which rather unusually do not produce any new viral particles.
Hi all,
I know that the Lerner and Beqaj theory of abortive EBV infection is widely promoted in this forum. However, while Lerner and Beqaj have published an ‘hypothesis paper’ on this theory (Virus Adaptation and Treatment 2012:4 85–91), as yet, it doesn’t appear to be supported by any solid science.

It is important to point out that there is nothing wrong with Lerner and Beqaj publishing "hypothesis papers". Such papers are important for stimulating new ideas and new research. But hypotheses should not be conflated beyond what they seek to provide:- An interesting hypothesis that is worthy of scientific investigation. To date, the proposals made in their 'hypothesis paper' havent been confirmed clinically. Thus, such hypothesis papers shouldn’t be mistaken for actual robust scientific evidence.

But I think it is worth discussing some of the key ideas and whether they may be relevant to CFS.

Firstly, I think some of the confusion with the abortive EBV infection hypothesis is centered on how viral serology is clinically interpreted. In most instances, the presence of a particular antibody in the serum of an individual is simply a historical record of an invasion by foreign pathogen (there are some notable exceptions such as the presence of autoantibodies). From the time an EBV virion infects a cell to the time the infected cell bursts open to release 10,000s of infectious viral particles, EBV will produce nearly 100 different proteins. Some proteins are produced early during the infection (eg. Early Antigen, EA), some are produced later (eg. EBNAs), and some are produced even later and are required for viral replication (eg. EBV dUTPase, and EBV DNA polymerase). Because serology reflects the historical record of infection, EBV serology is simply the sum total of all the anti-EBV antibodies that have been produced from the first EBV infection, to Infectious Mononucleosis (IM) and finally during recovery from IM.

Some of the EBV serology profiles and their interpretation is pasted in the table below (from J of Virol, 12:1-31). I have highlighted the serological pattern of @.jm. Note that table indicates either i) acute infection or ii) non-specificity. My suggestions earlier also included a 3rd possibility that might involve the expansion of a lymphocyte clone. The recommendation in the table is "further testing required' which I agree is very important in any cases with anomolous EBV serological profiles.
upload_2018-1-17_15-51-29.png


ANYWAY, getting back to the hypothesis of Lerner and Beqaj. Essentially it fails to recognize that the presence of a particular antibody cannot be used to diagnose specific types of infection such as latent infection, abortive replication or even sporatic/partial EBV reactivation.

Using their specific example, they propose:

“A small group of six patients in the group-A EBV subset of CFS, additionally, had repetitive elevated-serum titers of antibody to the early lytic replication-encoded proteins, EBV dUTPase, and EBV DNA polymerase. The presence of these serum antibodies to EBV dUTPase and EBV DNA polymerase indicated EBV abortive lytic replication in these 6 CFS patients.” (Virus Adaptation and Treatment 2012:4 85–91)(my bolding)

Unfortunately, such a conclusion cannot be made. “The presence of serum antibodies to EBV dUTPase, and EBV DNA polymerase..” simply means that sometime in the past, the individual has been infected with EBV and that the virus has produced dUTPase and DNA polymerase in order to replicate (my bold). The virus may have produced dUTPase and DNA polymerase during:
  • a primary infection,
  • abortive replication or
  • EBV reactivation.
The mere presence of antibodies to dUTPase and DNA polymerase doesnt allow these 3 very different scenarios to be distinguished. While the presence of IgG antibodies to EBV dUTPase and DNA polymerase would indicate a past infection, it doesn’t allow the differential diagnosis of which type of infection, when it occurred or even whether it might be ongoing.

There is also another common misunderstanding in terms of EBV serology. Antibodies against foreign pathogens can persist for decades in the circulation. So the presence of antibodies to EBV replicative proteins may have nothing to do with abortive replication. Their presence in the circulation may simply represent an historical record of viral infection and replication that occurred many years beforehand.

Another common misconception is the clinical significance of EBV antibody titres. Some CFS practitioners contend that high EBV antibody titres indicate ongoing active infections. However, the clinical reality is that EBV antibody titres dont allow differential diagnosis of CFS and certainly dont allow identification of abortive replication. The simple reason is that each person's immune system reacts very differently to foreign antigens and so antibody titre doesnt provide a reliable diagnostic tool for identifying abortive replication. This critical point has been made in several studies investigating EBV antibody titres and CFS (J. Med. Virol. 82:1684-1688)(Journal of Molecular Diagnostics, Vol. 3, No. 1).

To illustrate this point, a person with a past EBV infection who is perfectly healthy may have a high IgG antibody titre to a particular EBV protein while a person diagnosed with post-EBV CFS may have a low IgG antibody titre to the same protein. The exact opposite scenario can also occur in a different individual. Thus, in each individual, the diagnostic conclusion would be simply that each person has had a past EBV infection. While serology is very helpful in accurately distinguishing between i) EBV naive, ii) acute EBV infection and iii) EBV past infection, it doesnt provide a reliable diagnostic indicator of latent, abortive or even reactivated infection (NEJM, 343:7, 481).

For these reasons, “repetitive elevated-serum titers of antibody to the early lytic replication-encoded proteins, EBV dUTPase, and EBV DNA polymerase” as proposed by Lerner and Beqaj would not reflect abortive replication in CFS. Again, it simply reflects an historical record of a past infection where viral replication occurred.

Abortive infections can be ongoing chronic infections......
This is not really true. Chronic Activated EBV infections are a distinct diagnostic category and entirely different to EBV-related CFS and are not considered Abortive Infections. But, it is true that in Chronic Activated EBV infections, viral titres may actually be important diagnostically. For example, high EBV antibody titres have been identified in Chronic Active EBV infection. In addition, high EBV antibody titres can be considered 'red flags' for some EBV-mediated tumors including lymphomas and nasopharangeal carcinomas.

However, these conditions have different diagnostic criteria to CFS and are entirely different diseases. For example, Chronic Active EBV infections are ii) a serious medical condition that requires immediate medical intervention, ii) characterized by significant morbidity and mortality and iii) a distinct and recognizably different pathology to CFS (American Journal of Hematology 80:64–69). The term 'Chronic Active EBV infection' is often mistakenly used to describe some types of CFS that arise from a EBV infection. However, such medical terminology is misleading.

The clinical features of Chronic Active EBV infection include i) ongoing non-resolving IM symptoms (the diagnostic features of CFS and IM are different), ii) unusual patterns of EBV antibodies, iii) high anti-EBV antibody titres (high antibody titres are not considered diagnostic feature of CFS), and iv) high viral load in the serum/plasma (CFS patients dont generally have high viral loads in serum or plasma). Again, patients with Chronic Active EBV infections are incredibly sick, have high mortality rates and the disease is clinically distinct from CFS. The 2 conditions should not be confused.

One last caveat! We shouldnt completely exclude the possibility that some EBV serology profiles may have diagnostic potential in at least some subsets of CFS patients. For example, it appears that EBNA IgG antibodies are not generated in at least some CFS patients (cant find the ref for this, but i'll try and dig it up). It may be that failure to generate EBNA IgGs allows ongoing latent EBV infections that that predispose to CFS.

Question: Are many EBV-related CFS patients here EBV VCA-IgG-positive but EBNA-negative?

Rodger
 

Attachments

  • upload_2018-1-16_17-9-58.png
    upload_2018-1-16_17-9-58.png
    36.2 KB · Views: 22

bspg

Plant Queen
Messages
547
Location
USA
For these reasons, “repetitive elevated-serum titers of antibody to the early lytic replication-encoded proteins, EBV dUTPase, and EBV DNA polymerase” as proposed by Lerner and Beqaj would not reflect abortive replication in CFS. Again, it simply reflects an historical record of a past infection where viral replication occurred.

Sorry if this is ignorance on my part, but can't historical record vs. active/recent infection be distinguished by the presence of IgM antibodies?
 

bspg

Plant Queen
Messages
547
Location
USA
Also, what if a patent has elevated, abnormal EBV antibody patterns for multiple years but is always negative on PCR?
 

Hip

Senior Member
Messages
17,820
I know that the Lerner and Beqaj theory of abortive EBV infection is widely promoted in this forum.

Actually the abortive herpesvirus infection theory of ME/CFS has not been promoted at all on this forum — as a forum search on the word "abortive" will verify.

I only properly understood this abortive infection theory a few months ago when I spent some time reading about it, and wrote a thread on it. I only started talking about this theory on the forum in the last two months. Prior to this, the theory was almost never mentioned on this forum, and I expect very few people knew and understood this theory on this forum. That's why I am making the effort at the moment to introduce the theory.



But hypotheses should not be conflated beyond what they seek to provide:- An interesting hypothesis that is worthy of scientific investigation.

It is still a hypothesis at this stage, agreed, but when patients are trying to understand why they have high EBV titers, but a negative PCR blood test (ie, no EBV virus in the blood), and thus wonder whether perhaps they don't have any EBV infection after all, it's good to introduce the abortive infection hypothesis, because the beauty of this hypothesis is that it provides a plausible explanation of these lab findings. The theory indicates that you can still have a chronic abortive EBV infection in the tissues even though there is no virus in the blood.

In other words, once you understand the concept of an abortive infection, you realize that you don't have to have lots of viral particles in the blood in order to have an infection.



Unfortunately, such a conclusion cannot be made. “The presence of serum antibodies to EBV dUTPase, and EBV DNA polymerase..” simply means that sometime in the past, the individual has been infected with EBV and that the virus has produced dUTPase and DNA polymerase in order to replicate (my bold). The virus may have produced dUTPase and DNA polymerase during:
  • a primary infection,
  • abortive replication or
  • EBV reactivation.
The mere presence of antibodies to dUTPase and DNA polymerase doesnt allow these 3 very different scenarios to be distinguished.

Perhaps the presence of dUTPase on its own does not distinguish between abortive infections, and primary / reactivated infection.

But if you add in the fact that there is no viremia and usually little virus to be found in the blood in enterovirus or herpesvirus ME/CFS, then that tends to rule out primary or reactivated infection.

I have to admit I don't understand the dUTPase findings in ME/CFS patients that well, though.



However, the clinical reality is that EBV antibody titres dont allow differential diagnosis of CFS

Agreed. High titers to ME/CFS-associated viruses are found more frequently in ME/CFS patients than in healthy controls, but because these high titers are also found in controls, they cannot be diagnostic for ME/CFS.

But the reason ME/CFS doctors test for viral infections in ME/CFS is not for the purpose of making a ME/CFS diagnosis, but rather for the purpose of determining which antiviral / immunomodulator would be appropriate for treating the patient.

So for example if you have high titers to EBV, Valtrex may be prescribed. If you have high titers to cytomegalovirus, Valcyte may be prescribed. Determining which antiviral to prescribe is the main reason for viral testing in ME/CFS.



Antibodies against foreign pathogens can persist for decades in the circulation. So the presence of antibodies to EBV replicative proteins may have nothing to do with abortive replication. Their presence in the circulation may simply represent an historical record of viral infection and replication that occurred many years beforehand.

Antibodies can persist for decades, but in ME/CFS patients you find that there are often elevated antibody titers, suggesting this is not just from a past infection, but due to current infection activity.

In the case of herpesvirus ME/CFS, I agree that there is very little evidence for abortive infection. However, in enterovirus ME/CFS, there is ample evidence for an abortive infection of sorts, namely enterovirus non-cytolytic infection, which can be thought of as a species of abortive infection (non-cytolytic infections do not produce viral particles).

The British research on enterovirus ME/CFS in the 1990s found enterovirus RNA in the muscle tissues of ME/CFS patients, but could never culture the virus from these tissues, indicating that the muscle infection was not a regular productive infection which produces new viral particles. We now understand that these muscle infections are due to non-cytolytic enterovirus.

Unfortunately during the 1990s, nobody knew about non-cytolytic enterovirus infections; that is only a more recent discovery.

But let's be clear: for enterovirus-associated ME/CFS, there is ample evidence for abortive (ie non-cytolytic) enterovirus infection.



For example, Chronic Active EBV infections are ii) a serious medical condition

I know there is a difference between chronic EBV infection, a rare but significant disease, and EBV-associated ME/CFS. According to Lerner's theory, the difference is that the former involves productive infection producing new viral particles, and the latter involves abortive infection producing no new viral particles.
 
Last edited:

Hip

Senior Member
Messages
17,820
Also, what if a patent has elevated, abnormal EBV antibody patterns for multiple years but is always negative on PCR?

Under Dr Martin Lerner's abortive infection theory of ME/CFS, such results can be interpreted as the ME/CFS patient having a chronic abortive EBV infection in the tissues, which the immune system responds to, hence the high EBV antibody titers.

Antibody tests do not detect the virus directly, but measure the degree of immune response to the virus. If the immune response is high (elevated titers), then that suggests an ongoing viral infection.

However, because abortive infections do not produce any new viral particles, you find very few viral particles in the bloodstream, hence the negative PCR blood test (PCR detects the presence of the virus directly).
 
Last edited:

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
For these reasons, “repetitive elevated-serum titers of antibody to the early lytic replication-encoded proteins, EBV dUTPase, and EBV DNA polymerase” as proposed by Lerner and Beqaj would not reflect abortive replication in CFS. Again, it simply reflects an historical record of a past infection where viral replication occurred.

Thank you @rodgergrummidge for helping to clear up some of confusion about high antibody titers.

Jim
 

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
Antibody tests do not detect the virus directly, but measure the degree of immune response to the virus. If the immune response is high (elevated titers), then that suggests an ongoing viral infection.

The elevated titers could also be suggestive of the immune system dysfunction in ME/CFS.

Robert Naviaux says it's because the balancing T-cell and NK cell mediated immune activity is decreased in CFS. This is a functional kind of immune deficiency that causes an unbalanced increase in antibodies.

Jim
 

Hip

Senior Member
Messages
17,820
Thank you @rodgergrummidge for helping to clear up some of confusion about high antibody titers.

It has not cleared it up, as @rodgergrummidge is only expressing his opinion that these high titers only reflect past infection, but this is not a proven fact.

Nobody knows what high EBV titers mean in ME/CFS; they could just be due to past infection now under control, or they could be due to an ongoing infection, like the chronic abortive infection proposed by Dr Lerner.



The bottom line though is that when such EBV high titers are found, antiviral treatment with Valtrex or Valcyte has been shown in published studies to lead to major improvements in ME/CFS.

So whether you believe in chronic EBV infections in ME/CFS or not, the fact is that those with high EBV titers respond to antivirals, and that's what is important from the ME/CFS patient's perspective.
 

Hip

Senior Member
Messages
17,820
Robert Naviaux says it's because the balancing T-cell and NK cell mediated immune activity is decreased in CFS. This is a functional kind of immune deficiency that causes an unbalanced increase in antibodies.

Yes, this is possible, but these are all theories and hypotheses at this stage. The high titers could be due to immune dysfunction, or they may really be indicating an ongoing infection.

As I say, when you give antivirals to ME/CFS patients with high titers, they often improve. So from the practical treatment point of view, high titers = an opportunity to treat ME/CFS with an antiviral and make a substantial improvements in health.
 

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
So whether you believe in chronic EBV infections in ME/CFS or not, the fact is that those with high EBV titers respond to antivirals, and that's what is important from the ME/CFS patient's perspective.

I think and hope that most people with CFS want both symptom relief AND to know the truth about what is causing their symptoms.

If I know why I'm getting relief from an antiviral and it's not from it's antiviral properties, I can further investigate that and hopefully gain better health and recovery from doing so.

I have read that antivirals help some people with CFS, to varying degrees and I believe that's true. However, if it is doing it through some other mechanism other than treating chronic EBV infections, that is a very important distinction to be made.


Jim
 

Hip

Senior Member
Messages
17,820
I think and hope that most people with CFS want both symptom relief AND to know the truth about what is causing their symptoms.

We certainly want to know the truth about what is causing ME/CFS, but unfortunately that truth will only come from further research.

Careful postmortem studies on ME/CFS patients I expect could reveal whether there are abortive herpesvirus infections present. And so probably could muscle biopsy studies. One such muscle biopsy study found EBV DNA in these muscle tissues: see this 1991 study. Although the study says the EBV in muscle could have been due to infiltrating B cells.



However, if it is doing it through some other mechanism other than treating chronic EBV infections, that is a very important distinction to be made.

Agreed.

One type of study that could verify whether the benefits of herpesvirus antivirals are really due to their antiviral action, or due to some other non-viral mechanism, would involve giving an antiviral like Valtrex to both active EBV and non-EBV ME/CFS patients.

If it were the antiviral effect that provided the benefits, then you would only expect to see improvements in the EBV patients. Whereas if it were due to some other effect, then you would expect to see equal improvements in both groups.
 

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
We certainly want to know the truth about what is causing ME/CFS, but unfortunately that truth will only come from further research.

I agree. Have you seen the bolg @paolo just posted about Mark Davis's ongoing research into finding a pathogen or autoimmune disease? It's a very extensive and detailed write up!

As such, this test – that I have named the universal immune testing – seems to have the potential to determine if a given patient has an ongoing infection (and the exact pathogen) or an autoimmune disease (and the exact autoantigen, i.e. the tissue attached by the immune system).
https://paolomaccallini.wordpress.c...and-the-search-for-the-universal-immune-test/

Jim
 

rodgergrummidge

Senior Member
Messages
124
It has not cleared it up, as @rodgergrummidge is only expressing his opinion that these high titers only reflect past infection, but this is not a proven fact.

Nobody knows what high EBV titers mean in ME/CFS; they could just be due to past infection now under control, or they could be due to an ongoing infection, like the chronic abortive infection proposed by Dr Lerner.
.
@Hip has suggested that in my previous post I was expressing my Opinion. Opinions may be based on many things including hunches, anecdotes, personal experience and implicit biases? Thus, when it comes to medicine and health, opinions can be very unreliable because they are simply assertions that may be based on implicit biases and beliefs.

So what place does individual Opinion hold in our efforts to find potential diagnostics and treatments? How much weight should be placed on any one person’s opinion? And importantly, how do we distinguish the difference between a ‘personal opinion’ and actual ‘scientific evidence’?

Being able to distinguish ‘personal opinion’ from actual ‘scientific evidence’ is critical as we all chart our own personal course in CFS. Being able to source high quality scientific information gives us the best prospect of significant improvements in CFS symptoms. But if we follow potentially unfounded Opinions, we can put our already tenuous health at significant risk.

On the other hand, if someone makes an argument based on published scientific evidence, they are not simply expressing their Opinion (or anyone else’s). They are making an argument based on available scientific Evidence.

So to return to hypothesis proposed by @Hip: High antibody titres to viruses might be diagnostic for abortive EBV infections in CFS? Its certainly an interesting hypothesis that could be plausible.
To illustrate this point, a person with a past EBV infection who is perfectly healthy may have a high IgG antibody titre to a particular EBV protein while a person diagnosed with post-EBV CFS may have a low IgG antibody titre to the same protein. The exact opposite scenario can also occur in a different individual. Thus, in each individual, the diagnostic conclusion would be simply that each person has had a past EBV infection. While serology is very helpful in accurately distinguishing between i) EBV naive, ii) acute EBV infection and iii) EBV past infection, it doesnt provide a reliable diagnostic indicator of latent, abortive or even reactivated infection (NEJM, 343:7, 481).

My comment above is not my personal Opinion. My comment seeks to summarize scientific Evidence reported in the quoted citation. In my assessment of the scientific/clinical evidence, some may disagree my interpretation of data, the methodology used in the publication, the reproducibility of the work or some other aspect of the research. But the discussion would be based on the scientific evidence. Not my personal Opinion.

Similarly, below, I am not arguing my personal Opinion. Rather, I am trying to summarize the published findings in the cited references.
Another common misconception is the clinical significance of EBV antibody titres. Some CFS practitioners contend that high EBV antibody titres indicate ongoing active infections. However, the clinical reality is that EBV antibody titres dont allow differential diagnosis of CFS and certainly dont allow identification of abortive replication. The simple reason is that each person's immune system reacts very differently to foreign antigens and so antibody titre doesnt provide a reliable diagnostic tool for identifying abortive replication. This critical point has been made in several studies investigating EBV antibody titres and CFS (J. Med. Virol. 82:1684-1688)(Journal of Molecular Diagnostics, Vol. 3, No. 1).

No scientific study is perfect and most will have a number of limitations. In my discussion of the diagnostic value of EBV antibody titres, I also highlighted some of the clinically relevant exceptions were high antibody titres to EBV can be diagnostic for some serious medical conditions including chronic active EBV infections and some cancers and included a further cited reference. Such EBV-related diseases are not based on abortive infections. Again, I was not stating my personal opinion. I was summarizing scientific evidence based on cited scientific publications.
For example, high EBV antibody titres have been identified in Chronic Active EBV infection. In addition, high EBV antibody titres can be considered 'red flags' for some EBV-mediated tumors including lymphomas and nasopharangeal carcinomas.....(American Journal of Hematology 80:64–69).

The wonderful thing about science is that it asks people to ignore their opinions and biases and simply assess the evidence.
Antibodies can persist for decades, but in ME/CFS patients you find that there are often elevated antibody titers, suggesting this is not just from a past infection, but due to current infection activity.
what is the evidence?

But let's be clear: for enterovirus-associated ME/CFS, there is ample evidence for abortive (ie non-cytolytic) enterovirus infection.
I am not aware of any ample evidence of abortive viral infections playing a role in ME/CFS? what is the evidence?

As I outlined earlier (with citations), antibody titres can vary widely in both healthy and diseased populations (apart from some notable exceptions I cited). High viral antibody titres can occur in a healthy individual. Low viral antibody titres can occur in a diseased individual. You see the confounding diagnostic criteria?

I know many believe that antibody titres to specific viruses can be used diagnostically in CFS. Many pay commercial labs to get antibody titres which are then used to justify a range of treatments. But, because individual immune responses vary so widely, antibody titres are not an accepted diagnostic in virus-induced CFS patients, or in fact any CFS patient (again, apart from some noteable exceptions I cited).

Beyond Lerners Hypothesis Paper, what is the scientific evidence that abortive infections lead to high viral Ab titres (to replicative proteins?) and ME/CFS?

How would abortive infections in ME/CSF be specifically diagnosed from other conditions such as non-abortive infections in ME/CFS?

@Hip I hope you dont think I am having a crack. You make wonderful contributions to PR which are valued highly by myself and others. I just think that if someone has a particularly odd EBV serology (as in this thread), they should exclude the most likely diagnostic possibilities (some of which might be serious) before pursuing treatments based on a 'hypothesis paper'.

Rodger
 

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
what is the evidence?
Well, the evidence could be a positive PCR test (though I understand its not a perfect test either).

The attached 2 papers discuss situations where patients can have non-standard titers, leading to confusion in interpretation. (I think you may have been quoting one, @rodgergrummidge )

As a patient, its important to know whether you have EBV as it has indeed been implicated in both cancer and autoimmunity, and it is (mostly) treatable. And, with the confusion, many doctors miss this important diagnosis because they take a simplistic view of reading labs, even infectious disease doctors can miss it ...
 

Attachments

  • deficient EBV response.PDF
    2.3 MB · Views: 22
  • serological EBV diagnosis.pdf
    855.3 KB · Views: 37