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CDC: CFS not subject to opportunistic infections?!

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17
Hello,
As mentioned in another post (re: Dr. Wessely), I am new to this forum and have been "out of the loop" for a while until recently. My disease (CFIDS) was at least 90% in remission from 1997 until spring of 2013. I have discussed this in my blog, My Battle with CFIDS. My question is this: I was very surprised to learn that according to the CDC: " The opportunistic infections or increased risk for cancer observed in persons with immunodeficiency diseases or in immunosuppressed individuals is also not observed in CFS." ?! I find this very hard to believe, as I have struggled with chronic infections and this was, in fact, a big part of what led to my diagnosis of CFIDS in 1992! Dr. Mikovits has referred to CFS as "non-HIV AIDS" and this sounds pretty accurate based on my own experience and that of many other patients. I thought perhaps the CDC classified CFIDS as a separate disorder, but apparently not. Can anybody tell me why on earth the CDC does not acknowledge the immune dysfunction aspect of CFS??
 

Hip

Senior Member
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18,071
Chronic reactivated infections with viruses such as EBV, HHV-6, CMV, coxsackievirus B and echovirus are a typically found in ME/CFS, though the degree of reactivation may only be slight.

However, I would not have thought that these can be classed as opportunistic infections. In HIV/AIDS, opportunistic infections are quite severe. For example, cytomegalovirus retinitis is a sight-threatening infection that can occur in HIV patients who are not taking anti-retrovirals. And many HIV patients die of pneumonia as an opportunistic infection.

Here is a list of common opportunistic infections that cause morbidity and mortality to HIV patients.

I have not heard of any stories of ME/CFS patients who developed opportunistic infections that threatened life or caused significant morbidity.

And in some aspects, ME/CFS patients have super-immunity: many ME/CFS patients can go for years without catching a single cold (though others seem to catch every cold going). In ME/CFS some parts of the immune system can be ramped up, while other parts are under par.

I suppose you could argue that we have mild opportunistic infections in the form of gut dysbiosis.
 
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Aerose91

Senior Member
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1,401
I think one of the hallmarks ME is a chronic overactive immune system which is where many of the crappy symptoms come from. Other parts of the immune system seem depressed but that seems to be for other reasons, such as toxicity and cellular damage. I guess an overactive immune system can't be considered suppressed even though it generally works sub-par.
 

manna

Senior Member
Messages
392
Do the CDC actually recognise CFS as a physical condition? If not then what they say is to be taken with a pinch of salt. Testing for infection is not straightforward by any means. When I went to see a nurse for a hiv test, at the behest of my Doctor due to weight loss, the nurse told me that I had the hallmarks of someone who was hiv + or was undergoing chemo and hence displayed depressed immunity. This was basically due to geographic tongue with a candida infection all over it.

She told me to bring a friend for the results as she assumed It would be "positive". It was negative and she was genuinely intrigued to learn that it occurred the day following having a mercury filling placed. I consider that the toxicity from the filling (large amounts of mercury are released during the placement and removal of fillings) was more than my body could excrete and my immune system could handle and so whilst overloaded with that it was unable to check the migration of candida from the large intestine (where it lives in practically everyone, to the rest of the body.

This nurse obviously sees many individuals with suppressed immunity. Also nurses have a different remit to doctors so less agenda maybe. I told my Doctyor and he just brushed it aside. When I mentioned that my previous Doctor at the same practise had diagnosed "Geographic Tongue" he was like...oh it comes and goes. He had no idea what it was....but then Doctors don't know much about specfic health conditions anyway. It's very easy to do a little research and be more knbowledgeable than them on many conditions.

I haven't had a genuine flu or viral infection since getting M.E. and I'd guesss that others havenn't. Blocked noses and the like are things like constipation and/or a state on constant internal phlegm that due to environmental factors and overdoing, gets worse occasionally but I don't see it as further infection; in the sense of one that the body is fighting. I tested negative for candida, even though everyone has it and clearly it was all over my mouth and evenm a head scratcher for the Doctor at the time.

I don't see my immune response as overactive in any way. Generally the idea, from conventional medicine, was that you could not become over run with microbes, viruses and yeasts without dying (correct that if wrong please). Germ theory is grossly misunderstood in medicine. You could take a swab from anyone's nose and likely find many "deadly" germs yet we remain upright.

I'm sure there was a post somewhere that showed folk with mecfs lived 25 years less and had a higher incidence of cancer.
 

justy

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Chronic reactivated infections with viruses such as EBV, HHV-6, CMV, coxsackievirus B and echovirus are a typically found in ME/CFS, though the degree of reactivation may only be slight.

However, I would not have thought that these can be classes as opportunistic infections. In HIV/AIDS, opportunistic infections are quite severe. For example, cytomegalovirus retinitis is a sight-threatening infection that can occur in HIV patients who are not taking anti-retrovirals. And many HIV patients die of pneumonia as an opportunistic infection.

Here is a list of common opportunistic infections that cause morbidity and mortality to HIV patients.

I have not heard of any stories of ME/CFS patients who developed opportunistic infections that threatened life or caused significant morbidity.

And in some aspects, ME/CFS patients have super-immunity: many ME/CFS patients can go for years without catching a single cold (though others seem to catch every cold going). In ME/CFS some parts of the immune system can be ramped up, while other parts are under par.

I suppose you could argue that we have mild opportunistic infections in the form of gut dysbiosis.


I have not heard of any stories of ME/CFS patients who developed opportunistic infections that threatened life or caused significant morbidity.

Really? I am surprised that you have spent so much time on PR and not noticed the people here who do have immune system problems and get frequent infections.

The article on HIV you linked to concerns serious infections in HIV. It mentions Pneumonia - which I have had twice in the past 6 years and three times in my life. This has caused serious complications as I now have scarring in my lungs and suffer frequent upper and lower respiratory infections (which are serious)

It also mentions Oral thrush, which I have had a number of times - including oesophageal which is serious if left untreated.

People with M.E are subject to catching and being unable to clear bacterial infections. I have two confirmed as being chronic and possibly three (Lyme, Bartonella and Chlamydia Pneumoniae). Some doctors are finding that 90% of their M.E patients have a heavy bacterial infection load. These bacteria are capable of hiding from the immune system and causing it to down regulate, leaving us open to getting lots of other nasty things.

I also personally have a very persistent HPV infection, which someone with a normal immune system would have cleared - mine didn't clear after 7 years and meant I ended up with pre cancerous cervical changes which had to be operated on - I crashed from this procedure and never recovered.

My M.E doctor is so concerned about my immune system that he will be treating me with IV gamma globulin to give me a boost so that I can stop catching extra things on top of the infections I already have, and give my body a chance to fight them.
 

ukxmrv

Senior Member
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4,413
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London
Maybe because it's because PWME get "every day low key" infections or ones that the doctors don't test for or know about?

I'm thinking about the chronic sinus infection I had for years and still reocuurs. It was eating through and collapsing my sinus area (cat scan) until my GP referred me to an ENT specialist. Several GP's denied there was such a thing as a chronic sinus infection.

Then the bouts of

cystitis
pneumonia
tonsillitis
warts
fungal skin conditions and strange skin growths
HPV which keeps flaring and returning strange PAP smear results
a number of other embarrassing infections I won't go into here but keep coming back like vaginal bacterial infections

Numerous food poisoning type bugs that go on for years, some are identified eventually by the NHS such as Giardia

and the numerous visits to doctors office with acute viral symptoms to be told it is "just a virus" but never tested to see if that is true and what it is

My guess is that the lack of testing is a problem and the sum of all these "every day" things to the same person every single year isn't being taken seriously.
 

Jonathan Edwards

"Gibberish"
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5,256
Can anybody tell me why on earth the CDC does not acknowledge the immune dysfunction aspect of CFS??

I think the specific issue here is the distinction between having more of the sorts of infections that normal people can have, like candida, pneumonia, recurrent viral URTI and having the sorts of infections that essentially never occur in normal people - the opportunistic infections like widespread fungal bone disease or lung disease from non-virulent mycobacteria. I am not aware that ME or CFS patients have opportunistic infections. So I guess that ME/CFS is really not at all comparable to AIDS. It might be a worse thing to have to cope with, as has sometimes been said, but for different reasons.

And to be fair to CDC, evidence for lack of immunocompetence in ME/CFS looks to be more and more uncertain. As new groups of scientists start looking at ME/CFS they are tending not to find any major differences - as in the case of Mady Hornig and Ian Lipkin's screening study for viruses. And the laboratory evidence for immunodeficiency is inconsistent from lab to lab. My impression is that as quality control comes in to ME/CFS research a lot of this evidence will be found to be unsubstantiable. Around the table at the IiME Colloquium this year there was no agreement on ME/CFS patients as a whole having more infections. In fact there was a strong consensus that some patients seem to get a lot of common infections but others get less than expected. So CDC are reflecting the opinion of the scientific community as a whole.
 

Hip

Senior Member
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18,071
Really? I am surprised that you have spent so much time on PR and not noticed the people here who do have immune system problems and get frequent infections.

Did you notice that I wrote: "many ME/CFS patients can go for years without catching a single cold (though others seem to catch every cold going)".

There seems to be some variation in immune competence from one ME/CFS patient to the next. There also would appear to be variation in the different branches of the immune system, in even a single patient. A patient may have both mild immunosuppression and super-immunity at the same time. Richard van Konynenburg once offered an interesting hypothesis is why some ME/CFS patients become largely immune to colds.

In my case, I almost never seem to catch colds since developing ME/CFS. However, just months after catching an enterovirus that soon led to ME/CFS, I suddenly start getting lots of brown plaque on my teeth, and at the same time, I had a sudden onset of receding gums, ie, periodontitis. Prior to catching that virus my dental health was perfect, and my teeth never collected any brown plaque. But for the last 10 years since catching this virus, I always now have brown dental plaque.

Dental plaque is in fact the biofilm of oral bacteria, and thus the sudden appearance of considerable amounts of this brown plaque on many of my teeth suggests that my immune system has been weakened in this aspect, because it appears to be having difficulty in keeping my oral bacteria in check.

A number of friends and family who caught this same enterovirus from me also developed this sudden dental plaque deposition on their teeth within months. So this is not specific to ME/CFS.

Dentists often look at plaque and periodontitis as having a bacterial etiology, but in cases like mine its original cause would appear to be the acquisition of a new virus in the body that leads to some mild but chronic immunosuppression. (Though note that periodontitis may also be driven by connective tissue-dissolving enzymes like MMP-9 that attack the gums; secretions of such connective tissue-dissolving enzymes by the immune system can be increased by viral infections).


As an aside, regarding the the known association between cardiovascular disease and gum disease: some researchers have hypothesized that gum disease may lead to cardiovascular disease because they think bacteria from the gums may migrate to the heart and cause cardiovascular damage.

However, having observed how the enterovirus I caught precipitated both periodontal and cardiovascular problems in many people who caught it (4 previously healthy people out of the 30+ people who caught my virus had heart attacks, myocarditis or pericarditis, in most cases within months of catching the virus), I would suggest a more viable hypothesis: that a chronic viral infection such as mine causes both periodontal and heart disease simultaneously. Enteroviruses may be a major cause of sudden heart attacks: 16% of people who died suddenly of a heart attack were found to have a coxsackievirus B infection in their heart tissues.


The article on HIV you linked to concerns serious infections in HIV. It mentions Pneumonia - which I have had twice in the past 6 years and three times in my life. This has caused serious complications as I now have scarring in my lungs and suffer frequent upper and lower respiratory infections (which are serious)

Have you ever been tested for Chlamydia pneumoniae infection? This can cause pneumonia.

Chlamydia pneumoniae can be considered one of the known causes of ME/CFS, and is quite treatable one too (though you may need to be on antibiotics for a long time). Dr Chia estimates that Chlamydia pneumoniae is the cause of ME/CFS in 9% of his patients. So this is quite common cause of ME/CFS it seems.

Chlamydia pneumoniae is found in a latent state in 74% of the adult population, and about 10% of the population have a persistent active infection with this bacterium, according to a study conducted in Israel.
 
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justy

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@Hip yes I am positive for Cpn (chronic).

I wasn't referring to colds and mild infections, but more serious ones such as pneumonia. I am currently embarking on a long combined antibiotic protocol - I also have Bartonella and possible Lyme. My doc is treating with IVIG as well as Antibiotics.
 

Hip

Senior Member
Messages
18,071
@justy

Well in the UK the annual incidence of pneumonia is 6 cases for each 1000 people (in the 18 to 39 age group). So to say that ME/CFS patients are more prone to opportunistic infection with pneumonia, presumably you'd have to show that ME/CFS patients as a group get more cases of pneumonia than this UK average.

(Though you might need to exclude from that UK average people with immunocompromised conditions, so that the average only includes healthy people).
 
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Messages
17
thx for all your thoughtful replies! I guess I should clarify:

By "opportunistic infections" I am referring to any organism (bacterial, viral or fungal) that would not become aggressive or symptomatic in a person with a properly functioning immune system - such as I was prior to getting CFIDS! or even as I was during the 15 years that my disease was in remission. As discussed in my blog, prior to CFIDS I rarely if EVER got sick, even when everyone around me was sick. If anything I might catch a mild case [of whatever was going around] that would last for a day or two, but that was rare. After CFIDS I caught every cold or flu going around, and got it BAD, often evolving into pneumonia. If anybody coughed on the other side of the room, I caught whatever they had. I also got frequent sinus and ear infections, skin breakouts of uncertain etiology, and recurrent candida (which naturally was aggravated by all the antibiotics for the bacterial infections).

During the 15 years that my disease was in remission I became somewhat more resistant to infections, although not quite back to my fabulous pre-morbid state of health. Since my relapse in the spring of 2013 I have once again become very prone to contagions. For example, I caught strep throat from my step-daughter who is an "asymptomatic carrier"! Asymptomatic carriers of strep (about 15% of kids), after thorough antibiotic treatment, are generally NOT contagious except to people who are immunocompromised. I caught what appeared to be a community acquired pneumonia from somebody who was coughing 10 feet away from me and was very sick for over a month. I am also having frequent flare-ups of HSV, candida and skin lesions.

So that is what I meant. Although merely "anecdotal" my experience clearly demonstrates reduced immune function. For this reason, when my doctors allowed me to return to work, they specified that I should not work in an office setting or with the public. I work from home via internet and phone.
 

Hip

Senior Member
Messages
18,071
@metalnun

It seems that you fall into the category of an ME/CFS patient that "catches everything going," rather than the category of ME/CFS patient with super-immunity to colds.
 

alex3619

Senior Member
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13,810
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The only opportunistic infection we get on occasion (and this is anecdotal, I have yet to confirm it) is HHV8 induced Karposis sarcoma. Please note that the CDC is probably referring to acute viral infection. That is what they mean. They ignore risk of reactivation (because in part the evidence is patchy) and many other issues. So they speak the "truth" and lie with it at the same time ... or to put it another way, its a deceptive "truth".

I don't think we are at much higher risk for weird infections. What I think is much more likely is we have atypical responses to infections. This is probably in part due to poor NK cell function, but the infection/inflammation/immune thing is still unresolved.

On the other hand the evidence is now credible that we are at higher risk for lymphoma, not from CFS or ME surveillance but a large cancer cohort some years back, in the US I think.

So this is sleight of hand in a way. CDC ignore us because of lack of evidence of weird acute viral infection. Virus lifecycles other than the lytic lifecycle are ignored. Response severity is ignored. Post infection issues like Karposis sarcoma are ignored. So yes, we don't have good evidence of abnormal acute viral infections ... so what? What about all the rest. This is dogma in action, but then the CDC is a bureaucratic organization - such organizations typically love dogma.

Currently we have three leads that are looking much more solid with new technology and understanding. We appear to respond well to Rituximab, which depletes B cells. Our NK cells in serum/plasma have low cytotoxicity and motility. Our microglia have inflammatory markers. These all point to an immune issue. What we lack is a unifying theory that has been tested and found to be robust. It will happen though ... probably this decade. Maybe not this year.

PS I forgot to mention that case series studies with antiviral show a much better response than CBT/GET, an order of magnitude better, but are ignored because they are not RCTs.
 
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justy

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@justy

Well in the UK the annual incidence of pneumonia is 6 cases for each 1000 people (in the 18 to 39 age group). So to say that ME/CFS patients are more prone to opportunistic infection with pneumonia, presumably you'd have to show that ME/CFS patients as a group get more cases of pneumonia than this UK average.

(Though you might need to exclude from that UK average people with immunocompromised conditions, so that the average only includes healthy people).
Thanks for the link, it was really useful to read how I SHOULD have been treated when I was ill with pneumonia.

Just to clarify, I didn't say M.E patients en masse where subject to these types of infections, but was just pointing out that I had had them, in response to you saying you didn't know ANY M.E patients who had these kinds of infections. We don't all have up regulated immune issues, some of us are the opposite and are endlessly ill with bugs and illnesses on top of the ME that we can't clear ourselves, such as the chronic HPV that both myself and UKXMRV have suffered from and reported here.
 

Hip

Senior Member
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18,071
Just to clarify, I didn't say M.E patients en masse where subject to these types of infections, but was just pointing out that I had had them, in response to you saying you didn't know ANY M.E patients who had these kinds of infections. We don't all have up regulated immune issues, some of us are the opposite and are endlessly ill with bugs and illnesses on top of the ME that we can't clear ourselves, such as the chronic HPV that both myself and UKXMRV have suffered from and reported here.

Well what I said was true at the time of writing! ;-) Though now I can say I know one patient, yourself, who experienced a serious infection. What I mean in general is that serious or unusual infections are not the sort of things that come up as regular topics on this forum, unless I have been too blind or too brain fogged to see them.

In the case of these chronic human papillomavirus infection, again you would need to look at the incidence of persistent HPV in the general population, and then see if ME/CFS patients as a whole had higher rates of persistent HPV than the general population.


Of course it could be that certain subtypes of ME/CFS patient are more susceptible to common infections, and that other subtypes of ME/CFS patient are less susceptible to common infections. And anecdotally that seems to be the case.

Then if you performed a study on infection susceptibility on a group ME/CFS patients, you results might be skewed, because those with more infections would tend to cancel out those with less in the study, and on average, the study would conclude that as a group, ME/CFS patients are not more susceptible to common infections, but nevertheless there could be subtypes who are more susceptible.

What might be interesting is preselecting a cohort of ME/CFS patients who claim they catch every cold or infection in circulation, and then study them as a sub-group, to see if they have a history showing higher rates of susceptibility to common infections.


In any case, I think the correct phrase that might apply to subtypes of ME/CFS patients is "more susceptible to common infections" rather than the phrase "susceptible to opportunistic infections."

The dictionary defines opportunistic infections as:
An infection by a microorganism that normally does not cause disease but becomes pathogenic when the body's immune system is impaired and unable to fight off infection.
So as Prof Jonathan Edwards has indicated above above:

More susceptible to common infections = having more of the sorts of infections that normal people can have, like candida, pneumonia, recurrent viral URTI.

Susceptible to opportunistic infections = having the sorts of infections that essentially never occur in normal people, like widespread fungal bone disease or lung disease from non-virulent mycobacteria.

It's quite possible that there is a subset of ME/CFS patients who are more susceptible to common infections, and perhaps another subset who are less susceptible to common infections.

However, I don't think there is any subset of ME/CFS patients who experience opportunistic infections, by the definition of that phrase.


Though it might be interesting to study subtypes of ME/CFS patient who appear to be more susceptible to common infections. Whether such as study would lead to any further insights into the nature of ME/CFS, though, that's another issue.
 

Jonathan Edwards

"Gibberish"
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This issue of immunodeficiency is quite important to me because I am in the process of encouraging research colleagues to set up a further trial of rituximab. If ME/CFS really is associated with immunodeficiency we probably should not be doing that. I need to be sure I am not recommending something with unacceptable risk.

From what I can gather from the research workers in the ME field I have talked to we do not have reliable evidence of immunodeficiency on laboratory tests. There have been useful discussions with people like Professor Hooper and Charles Shepherd but nothing clear cut has emerged. I am aware that some change in lymphocyte function have been reported but it seems that none of these can be reliably reproduced. It does not seem that PWME are significantly at risk from the sort of opportunistic infections seen with AIDS. (I think we have to stick to the medical definition of opportunistic infection, which is different from suffering more from infections that normal people quite often get.) Clearly some people have had pneumonia but susceptibility to pneumonia, like influenza, is a strange thing. In the days before penicillin lobar pneumonia was known as a killer of fit and healthy adolescents or young adults. In the great influenza epidemics the fatalities were often in fit young men. Both conditions are also a risk for the immunocompromised such as the elderly and diabetics but the situation is not simple.

My Norwegian friends reassure me that their rituximab patients have not suffered serious infections. But I would still want to know if there was evidence of immunodeficiency that could be tested in the lab. My discussions with UK researchers indicate that no reliable tests exist. This might seem to conflict with views held by other researchers. However, in other fields where reliable tests do exist they become standard and the question is why that has not happened for ME. And I get the impression that even for other research groups opinions are shifting. I was interested to see that the CFIDS Association of America seems to have changed its name!

People have talked about what could actually be achieved in research terms by PR. I am very keen to pursue further research in direct communication with PWME and carers through PR. This is not a convention in science but maybe it is about time it was. It strikes me that there is no reason why PR should not be a forum in which issues like this one are thrashed out. So I would like to put out an invitation:

I am just about to propose putting together a protocol for a rituximab trial. If any researcher anywhere in the world can tell me how I can measure an immunodeficiency in ME patients that would mean we should not go ahead I would like to know. More than that, I need to know. So if anyone on PR knows of researchers who might be able to tell me of such tests then I would like to hear. They would have to be tests that satisfy quality control. I would want to be sure that if I sent 20 ME samples and 20 healthy samples on a blinded label basis there would be a clear difference between the two - say 80% of ME below a line and 80% of normals above. Does anyone think such tests exist? Wikipedia does not seem to think so and these things usually get on Wikipedia! Are there any researchers out there who want to offer?
 

Seven7

Seven
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I think at least in one case is for sure. If you google natural killer cell deficiency you will find is accepted and recognized that you will have viral reactivation of the Herpes viruses. So, I would think that at least if you confirm the Low NK cell sub-group you can bet for reactivation.

The patients that I know with Low Nk, had reactivation. Funnily enough the ones with normal NK did not show the same reactivation. The ones with Lyme, had different bacterial reactivations.

Just my personal observation and account from comparing results with other users.
 

justy

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@Jonathan Edwards What about the TH1 TH2imbalance that researchers/clinicians such as Professor Kenny De Meirleir is finding in his individual patients - is this important?

I believe he also finds high levels of chronic bacterial intracellular infections in his patient group - I have been diagnosed with chronic Bartonella, chronic Chlamydia Pneumoniae and possible Lyme disease. How do we go about using Rituximab in patients with possible long standing chronic, undiagnosed bacterial infections - is this even a problem?

Sorry, I am not a scientifically minded person, so not able to express myself terribly well, just doing my best to take part in an important discussion.

This is completely anecdotal, but we seem to have at least a subset of patients, like me, who are VERY susceptible to common infections and are constantly ill with one thing and another, but we don't seem to mount a proper immune response - in other words only from experience do I know that if I go near anyone with an illness I will catch it and then I will be ill with it for weeks, until eventually all these illnesses just join up into one long never ending illness. I also don't have the SEVERITY of illness that healthy people around me have. They have the short sharp shock type whilst mine waxes and wanes, lingers and makes my overall symptom picture worse.

I don't know how this can be tested for right now in the UK. But I do know that my M.E doctor from outside the UK is concerned enough about my immune system that he is suggesting IVIG for me.

Dr Nigel Speight at his pre dinner speech at Invest In ME this year also mentioned some studies that clearly show the efficacy of IVIG for M.E patients. Why would this help if there was not some sort of immune system issue.

I have realised recently that my good periods (which are rare) are simply the times when I have finished finally fighting off an infection or illness and haven't yet caught the next one. BTW my IgG is low normal and my subclasses are also mainly low normal.

My concern is that researchers wont see your plea for information here, but that doesn't mean they aren't interested in the Immune system in M.E.
 

Hip

Senior Member
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18,071
Natural killer cell function deficiency seems to be found in many ME/CFS patients, but I understand that there is no deficiency in the number NK cells in ME/CFS patients, but rather it is the activation/functioning of these cells that is low.

Here are some NK function ME/CFS studies:
Natural killer cell function in chronic fatigue syndrome
Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome
Decreased nitric oxide-mediated natural killer cell activation in chronic fatigue syndrome
Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis
Assessment of Natural Killer Cell Receptors and Activity in Severe and Moderate Chronic Fatigue Syndrome
Biomarkers in chronic fatigue syndrome: evaluation of natural killer cell function and dipeptidyl peptidase IV/CD26
Decreased natural killer cell activity is associated with severity of chronic fatigue immune dysfunction syndrome
Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

There is an article here by Cort Johnson on NK cells in ME/CFS.



Tests for NK activation/functioning are hard to find, and I believe they are expensive.

Redlabs in Belgium appear to have a NK cell function test (see here). And this thread lists some more labs that do NK cell function tests.

I am not sure just how well these NK cell function tests can discriminate between ME/CFS patients and healthy controls, and whether they might satisfy the 80% dividing line requirement you mentioned. There has been talk about using low NK cell functioning as a ME/CFS biomarker, so I presume the discrimination must be reasonable.



As for the shift to the Th2 response mentioned by @justy, here are a few papers on that:
Evidence for T-helper 2 shift and association with illness parameters in chronic fatigue syndrome (CFS)
High levels of type 2 cytokine-producing cells in chronic fatigue syndrome
A formal analysis of cytokine networks in chronic fatigue syndrome

A few ME/CFS doctors use immunomodulators that shift from the Th2 to the Th1 response, in order to better target intracellular infections.
 
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Hip

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18,071
And in terms of an explanation of why a subset of ME/CFS patients become largely immune to catching colds, a speculative hypothesis by Richard van Konynenburg may be of interest:

Why You Rarely Catch a Cold in ME/CFS

By Richard van Konynenburg

So first, how does the immune system normally respond to viral infections? There are basically four types of responses, listed here in roughly the chronological order in which they normally occur:

1. Type I interferon (interferons alpha and beta) responses
2. Natural killer cell response
3. Virus-specific cytotoxic T lymphocyte (CD-8 "killer" T cell) response.
4. Antibody response

Type I interferons are secreted by infected cells, to alert nearby cells, and hopefully prevent them from becoming infected. The Interferon responses include the PKR, the 2,5-OAS RNase-L, and the Mx responses, among others. The PKR response inhibits the synthesis of viral proteins inside host cells. The 2,5-OAS RNase-L response degrades viral RNA inside host cells. The Mx response inhibits viral gene expression and assembly of the virions inside host cells.

The natural killer cells recognize virally infected cells in which the viruses are attempting to hide from the immune system by shutting off the Class I HLA mechanism that the CD-8 cells use to recognize virally infected cells. If the Class I HLA molecules are not displayed on the cell surface, the NK cell kills the cell.

The CD-8 killer T cells kill cells that are displaying viral antigens by means of the Class I HLA molecules.

Antibodies against viral antigens are made by B lymphocytes and plasma cells, and they bind to viruses that are outside the host cells, as when an infection is beginning or when viruses are spreading from one host cell to another.

This neutralizes the viruses, so that they cannot enter new host cells, and it can also "mark" them for attack by other cells of the immune system, such as macrophages.

O.K., now what happens to these responses in ME/CFS?

Well, the Type I interferon responses continue to work, and even though they are intended to be short term responses to hold back the viral infection until the "cavalry" in the form of the CD-8 killer cells arrives, and the CD-8 cells, together with the NK cells, knock out the viral infection, in ME/CFS the interferon responses continue to work overtime (and even become dysregulated in the case of the RNase-L) because the CD-8 killer cells are not able to take over. Sadly, the "cavalry" never arrives, leaving the "civilians" to battle the "Indians" in an ongoing guerrilla war.

What causes the formation of the dysregulated low-molecular-weight RNase-L molecules? I propose that glutathione depletion is responsible. It activates calpain, and calpain cleaves the normal RNase-L molecules. The cleaved parts join together, forming the unregulated LMW RNase-L.

Both the NK cells and the CD-8 killer T cells are rendered impotent by their inability to make perforin and granzymes in normal amounts. Furthermore, the CD-8 killer T cells are not able to multiply to outnumber the "bad guys" as they should. Why does this happen? I propose that it is a result of glutathione depletion and depletion of folates, respectively, which are part of the GD-MCB vicious circle mechanism that I believe is at the basis of the pathogenesis of ME/CFS.

Antibody production continues, and in fact may be increased, because of the shift toward the Th2 immune response in ME/CFS, which favors humoral immunity, i.e. the production of antibodies by B lymphocytes and plasma cells. What causes this shift? Again, I have proposed that glutathione depletion is responsible, in this case in the "naive" T cells.

So what we have are heightened interferon and antibody responses, but failure of the main "kill" mechanisms. The result is that latent viruses in the body (such as EBV, CMV and HHV6) are able to reactivate, and the immune system continues to fight with the weapons it has left, confining the viruses and keeping the host alive, but not winning the war against the viruses by completely knocking them out or putting them back into latency.

Now, what about your questions?

Would interferon treatment work? Well, to some degree, but without the other dysfunctional immune responses to help them, they cannot completely knock out the viruses.

Why don't PWMEs get colds and flus? I think it's because of the constantly elevated interferon responses. This produces what has been called the "antiviral state." With this going on, it's difficult for a newly introduced virus to get a foothold.

Does this have anything to do with the elevated cytokines in ME/CFS? Yes. The immune system is well aware that there are enemies inside the perimeter, and it is sounding the alarm, trying to organize the defense. The cells of the immune system are sending chemical messages back and forth to each other in the form of cytokines. However, because the NK cells and the CD-8 cells are impotent, even though the trumpet sounds, they don't respond, because they are not able to, so the messages just keep flying back and forth, unheeded.

So what's the solution to this problem? How do we win the war? Well, I'm still working on that, but I think that a big part of it will be to restore glutathione, folates and methylation, and that will probably require a methylation protocol.

Beyond that, because viruses that are well-entrenched have various ways of foiling the immune system, even though the immune system is restored, other measures will likely also be needed. One interesting one is GcMAF, which overcomes one of the strategies used by viruses to foil the immune system, i.e. nagalase. Antivirals are another possibility, especially in view of some success using them, as in Dr. Lerner's experience.

I hope this is helpful.

Best regards,

Rich


Source: here.
 
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