Innate Immune Changes in the Peripheral Blood

[ukxmrv]

Dr Chia says that:


But I am not aware of any research that has been funded on investigating this acute infections + corticosteroids trigger for ME/CFS.

If corticosteroids given during an acute infection can trigger ME/CFS as often as Chia indicates, there really needs to be a change in guidelines issued to all doctors, regarding curtailing the prescription of corticosteroids unless really necessary.

I wonder if that would include inhalers for Asthma or any of the ingredients for Hayfever treatment?

When I was sick with ME at the very start it was an acute onset viral illness. High fever, sore, very swollen throat and tonsils, pus in throat, glands etc. It was severe and I was delirious.

One doctor gave me an Asthma inhaler as I was having problems breathing. Another gave me some form of allergy or hayfever medication but I was too sick at the time to comprehend what it was.

At the height of the illness (acute viral to the delirious and unconscious stage) I remember a doctor laughing at the allergy/hayfever medicine and throwing it in the bin. Then they started me on a course of antibiotics. I wasn't well enough even to see what it was.

There was no unusual stress at all for me prior to this acute onset.

Given that there is a EV outbreak at the moment in children in the USA I wonder how many of them will go on to develop ME?

 

[Sidereal]

Yes, if extreme stress leads to elevated cortisol and the attendant immune suppression, and one catches an ME/CFS-associated virus during that period of extreme stress, it may likewise allow the virus to insinuate itself more deeply into the body, such that even when immune strength returns, the virus is now too deeply dug in for the immune system to clear or control it.

Dr Chia uncovered this etiology of acute infections + corticosteroids = ME/CFS by careful and detailed questioning of his patients' histories just prior to them coming down with ME/CFS. Chia is stickler for taking full patient histories, as he thinks all the clues are there in the history.

This corticosteroid etiology of ME/CFS seems like a very important clue, and more research should be done on this.

That part of Chia's presentation etched itself into my mind. If ME/CFS really were an autoimmune condition then presumably the prednisone they got would have helped them or at least not made them worse.

 

[Gijs]

Dear professor Edward, One question: immunological findings are moderate to weak and inconsistent in ME. The only finding consitent is NK cell disfunction. What do you think about this finding? Thanks for your reply, Gijs

 

[Gijs]

Dear Professor Edward, Question number 2 Many people with ME have POTS. How do you think about this study?
J Am Heart Assoc. 2014 Feb 26; 3 (1): e000755. doi: 10.1161 / JAHA.113.000755.
Autoimmune basis for postural tachycardia syndrome.
http://www.ncbi.nlm.nih.gov/pubmed/24572257

Maybe you can focus on these findings because rituximab can help this group of patiënts, i think.

 

[MeSci]

That part of Chia's presentation etched itself into my mind. If ME/CFS really were an autoimmune condition then presumably the prednisone they got would have helped them or at least not made them worse.

Perhaps the autoimmunity can develop further down the line, e.g. due to a fall in endogenous cortisol production. If the HPA axis is infected, due to the initial low immune activity, then this could cause the drop in cortisol production, I think. (If my brain is functioning moderately well - it's a bit tired from wading through some scientific papers!)

So:

1. Low immune activity due to corticosteroids, stress and/or overexertion
2. Infection, whilst immune activity is still low.
3. Infection gets into brainstem.
4. Endogenous cortisol production falls.
5. Autoimmunity develops due to low cortisol.

Something like that. (Does that make sense, @Jonathan Edwards?)

 

[geraldt52]

I first got sick with what I eventually knew to be ME/CFS when my daughter was 2, when children constantly have one respiratory bug or another. I had always had low resistance to such things and was constantly catching whatever she had.

I would often develop secondary infections from these bouts with viruses or whatever and end up at the doctors. My only doctor at the time was my allergist, whose standard treatment for me was an antibiotic, a cortisone injection, and a course of prednisone. It wasn't unreasonable, because I had a history of asthma, and respiratory infections often ended up seriously in my chest. This repeated itself many times and I didn't think that much of it...until, the time I got really sick and the doctor's "standard treatment" didn't work. It was 1984. I never got better.

The point of all this is that the acute infections + corticosteroids = ME/CFS theory would absolutely fit me like a glove...even though I had never heard that theory. I really think there is something to the idea that it allows a "bug" to move into tissue that is inaccessible to the available treatments.

 

[Hip]

The point of all this is that the acute infections + corticosteroids = ME/CFS theory would absolutely fit me like a glove...even though I had never heard that theory. I really think there is something to the idea that it allows a "bug" to move into tissue that is inaccessible to the available treatments.

In Dr Chia's published studies, he talks about the persistence of non-cytolytic enterovirus infections in ME/CFS patients being likely a result of these infections getting into immune privileged cells. Immune privileged cells are protected from the full force of the immune attack, so once an infection gains entry into such cells, it's then hard to get the infection out. In his paper, Chia says immune privileged cells include macrophages, muscles, myocardial cells, and neurons.

One might hypothesize that if an acute enterovirus infection is given a major advantage because a patient is prescribed immune-suppressing corticosteroids, this may buy time for the virus, allowing the virus to get into these immune privileged cells, and into immune privileged organs and tissue compartments (like the brain).

The virus would then be harder to oust, because the immune system always goes softly-softly on immune privileged cells. So now you have a chronic infection — and a chronic disease.



Just as a reminder: normal lytic enterovirus infections comprises viral particles (virions) that circulate in the blood; but non-cytolytic enterovirus infections consist of bits of viral RNA that live inside human cells.

There is a current discussion on non-cytolytic enteroviruses going on in this thread.

 

[Hip]

If a person is fighting off a bacterial infection (I believe my illness started as food-borne illness) could that leave the immune system less able to deal with virus?

It's an interesting idea, but I am not sure if there is any evidence for such an etiology. Though ME/CFS does sometimes appear after food poisoning. The author of "Seabiscuit", Laura Hillenbrand, developed her ME/CFS after food poisoning.

 

[Hip]

I wonder if that would include inhalers for Asthma or any of the ingredients for Hayfever treatment?

When I was sick with ME at the very start it was an acute onset viral illness. High fever, sore, very swollen throat and tonsils, pus in throat, glands etc. It was severe and I was delirious.

One doctor gave me an Asthma inhaler as I was having problems breathing. Another gave me some form of allergy or hayfever medication but I was too sick at the time to comprehend what it was.

I guess you'd have to look at the dose of corticosteroids administered by asthma inhalers, and compare it to the typical oral corticosteroids doses. If it's a lot less, then the impact presumably would be less.

Also, if your asthma inhaler usage was just one off, it probably has much less impact than a prolonged course of corticosteroids that is taken for several days or even a few weeks.

Given that there is a EV outbreak at the moment in children in the USA I wonder how many of them will go on to develop ME?

Not all types of enterovirus are associated with ME/CFS. Coxsackievirus B and echovirus (which are both from the enterovirus B group) are associated with ME/CFS, but coxsackievirus A (from the enterovirus A group) is not.

This enterovirus outbreak in children in the US is due to enterovirus D68 (which is in the enterovirus D group).

This classifying of enteroviruses into groups A, B, C, D, etc is a new way of grouping them.


Enterovirus D68 is unusual in that it has characteristics of both enteroviruses and rhinoviruses (rhinovirus is a common cold virus). Enteroviruses are normally acid resistant, which enables them to replicate in the digestive tract. Rhinoviruses however are acid sensitive, and so are only found in the respiratory tract, not the digestive tract. This is why when you get a cold, you get respiratory symptoms, but not intestinal symptoms.

Enterovirus D68, like rhinoviruses, is acid sensitive, and so is only found in the respiratory tract.

 

[geraldt52]

There is a current discussion on non-cytolytic enteroviruses going on in this thread.

Thank you, Hip, for the explanation, and the link to the other thread. That is a very interesting theory...can't believe I hadn't heard it. It's sad that so many of us are likely to be carrying the clues that are needed to solve CFS, but there has been so little interest or urgency in following them. Thank you, CDC, NIH, HHS, for nothing. Actually, for doing worse than nothing.

 

[Jonathan Edwards]

That part of Chia's presentation etched itself into my mind. If ME/CFS really were an autoimmune condition then presumably the prednisone they got would have helped them or at least not made them worse.

I have been wondering about this association between giving steroid and subsequent ME. If the Dubbo study findings are right we have a potential bias problem. In general people with viral illnesses are not given steroids. I do not know about enteroviruses (I have never actually heard of steroids being given for them) but in EBV infection steroids are reserved for those who have severe features that persist despite initial observation. Dubbo tells us that these are exactly the people who are likely to get ME anyway, so the fact that they get given steroids does not necessarily mean the steroids had anything to do with it. You really have to have a double blind controlled trial of steroid or no steroid in severe cases and that would be very hard to set up.

If the severe reaction to a virus like EBV or enterovirus were a manifestation of an autoimmune process that was manifest as hyper-reactiveness to viruses then steroids might still help in the short term - as they tend to in people with EBV, even if later they may have prolonged fatigue. The patients DR Chia is worried about probably did get better initially, but then relapsed once the short term steroid course was stopped.

I find it quite hard to see how short courses of steroids would alter immune responsiveness in a way that would have long term implications. There are many thousands of people on long term steroids for autoimmune disease and there does not seem to be any indication that they lead to an ME/CFS picture. I think it is hard to know what is the chicken and what the egg here.

 

[Jonathan Edwards]

Dear professor Edward, One question: immunological findings are moderate to weak and inconsistent in ME. The only finding consitent is NK cell disfunction. What do you think about this finding? Thanks for your reply, Gijs

Even the NK findings are inconsistent. The one UK group I know that has studied this found no abnormality.Of the people who found abnormalities some found changes in numbers and others did not but found changes in killing assay activity. And when somebody else tried to repeat all this in another lab they found nothing I think. Moreover, the sorts of NK changes reported would not make me expect any major immune dysfunction in clinical terms. NK function is extremely variable and it is unclear it matters much unless you have a complete genetic defect in NK cell production - and in that situation there are problems with other cells too, as I understand it.

 

[Jonathan Edwards]

Dear Professor Edward, Question number 2 Many people with ME have POTS. How do you think about this study?
J Am Heart Assoc. 2014 Feb 26; 3 (1): e000755. doi: 10.1161 / JAHA.113.000755.
Autoimmune basis for postural tachycardia syndrome.
http://www.ncbi.nlm.nih.gov/pubmed/24572257

Maybe you can focus on these findings because rituximab can help this group of patiënts, i think.

We looked at this study in another thread. The findings are interesting but unusual for autoimmune disease. It is unusual to see antibodies to more than one target of a particular type in a single patient - here several receptors. I would like to see the findings replicated by another group.

 

[duncan]

Dr. Edwards, in terms of your response to Sidereal, steroids are usually contraindicated in cases of Lyme for precisely that reason, i.e. the steroids exacerbate symptoms and give rise to ME/CFS like features in Bb patients.

 

[Sidereal]

Thanks for your input, Dr Edwards. As far as I remember (it's been a while since I watched Dr Chia's presentation), he said that he's been able to elicit this sort of history from a number of patients: they got an enteroviral infection, sometimes this happened in the context of eating contaminated foods like shellfish or travelling, they got severely ill, presented to the hospital, the doctor fails to make the diagnosis of enteroviral infection and the patient is given prednisone for a presumed allergic reaction and never recovers from this initial illness, thus acquiring the diagnosis of CFS. It could be that steroids during this critical early period of infection allowed the virus to become entrenched in tissues like the CNS, muscles and GI tract where coxsackie likes to reside. Of course, as you say, it could be that they had a hyperreactive immune system to begin with and the severe infection is just a red herring and they were going to get slammed with ME at some point anyway. This thing about steroids being given to people with an enteroviral infection I've never heard anywhere apart from Dr Chia's talk which used to be on youtube but as @duncan said, this is common occurrence in the Lyme community where late-stage disseminated infection is often mistaken for the likes of RA or SLE and patients are given steroids, making them ultimately sicker.

 

[geraldt52]

...It could be that steroids during this critical early period of infection allowed the virus to become entrenched in tissues like the CNS, muscles and GI tract where coxsackie likes to reside. Of course, as you say, it could be that they had a hyperreactive immune system to begin with and the severe infection is just a red herring and they were going to get slammed with ME at some point anyway...

In my own case I don't think that my reaction in the final particular incident can be explained by a generally hyper-reactive immune system. Over the course of 5-7 years I had had the exact same antibiotic/cortisone/prednisone treatment I described above at least half a dozen times. It was always almost magically successful in treating the secondary infection that had settled in my chest, and at no time did I have any ill effects from the treatment....until the particular time that it did not do anything, and I never fully recovered. My doctor was baffled at the time, and repeated the treatment, once. When it did nothing again, he was completely baffled, and so began a years long journey involving dozens of doctors until I finally got the diagnosis of "Adult Fatigue Syndrome" around '89. It was exactly as though an infection had set in that was inaccessible to any treatment, and somehow eluded detection. I have always felt, and still feel, that's what "it" is.

 

[Hip]

@Jonathan Edwards
As @Sidereal mentions above, in Chia's videoed presentation, he introduces this corticosteroid etiology in the context of acute enterovirus infections being mistaken for an allergic reaction with a hives rash (enterovirus rashes can sometimes mimic hives), so that the emergency room doctor then prescribes the patient a course of corticosteroids

So it's not entirely clear whether this acute infection + steroids = ME/CFS etiology applies to all ME/CFS-associated viruses, including EBV, or just to enteroviruses.

 

[Hip]

I find it quite hard to see how short courses of steroids would alter immune responsiveness in a way that would have long term implications. There are many thousands of people on long term steroids for autoimmune disease and there does not seem to be any indication that they lead to an ME/CFS picture. I think it is hard to know what is the chicken and what the egg here.

I am just speculating here, but if corticosteroids are given when an individual is first coming down with a viral infection, at the stage before any antibodies to the virus have been produced (I understand it can take several days before the immune system can produce an antibody response to a newly-contracted microorganism), then might that result in the infection insinuating itself deeper into the body?

From Chia's descriptions of an enterovirus rash being mistaken for an allergy to shellfish that was eaten, and then treated with corticosteroids, it sounds like he's talking about the very first day or two of infection.


However, this does not really address your point that all the autoimmune disease patients on long term steroids do not seem to be coming down with ME/CFS, and over the years you would expect these patients to now and then contract an acute viral or enteroviral infection while on steroids.

 

[Jonathan Edwards]

This thing about steroids being given to people with an enteroviral infection I've never heard anywhere apart from Dr Chia's talk which used to be on youtube but as @duncan said, this is common occurrence in the Lyme community where late-stage disseminated infection is often mistaken for the likes of RA or SLE and patients are given steroids, making them ultimately sicker.

Yes it would seem that steroids in the context of enterovirus would likely be in the context of misdiagnosis. One would expect that to be only for 24-48hrs and that is a bit short to alter long term natural history I think - but possible. Lyme is of course a bacterial infection and the adverse effects of steroids in chronic bacterial infection are well recognised. Whether one would expect that to lead to an ME like syndrome I am less clear but I have had very little experience with Lyme.

 

[duncan]

Lyme disease is frequently misdiagnosed as other diseases, including MS, ALS, RA - the list runs on and on. In some of those misdiagnosed cases, steroids are prescribed, often in the more classic cases which present with swollen knees and the condition is mistaken for arthritis. Lyme researchers believe this worsens the disease. Regardless, eventually the correct diagnosis is usually reached, and treatment rendered. But many of these late stage cases (15 - 20%) don't respond to IDSA-recommended antibiotic therapy. The results, of course, is Post Treatment Lyme Disease Syndrome...and you'd be hard-pressed to find a more "ME like Syndrome" than PTLDS. (Take away arthritic knees, and Late Stage Lyme and ME/CFS could be mirror images of each other. A PTLDS sufferer is just a Lyme patient who has received some form of abx, and most clinicians would be challenged to distinguish between ME and PTLDS based on symptoms alone).

I do not believe a study has ever been done to look at what portion of PTLDS patients received steroids, or whether those that did are sicker than those that didn't. But it would make for some interesting data if an agency or group ever undertook to delve into the possibility.