Do MEs cause CFS?

[alex3619]

Interactive threads mean you can ask questions to clarify answers. In my case i am going to see if I can find any tests lurking around, though I have lost most of my tests from decades ago.

 

[Sasha]

It is actually one question in the strict rules of logic. I could put a 'both' in to make it clear. An answer yes has to mean a yes to both. But I am thinking we are not going to go for a technical poll anyway. If there is a thread we just get answers and if these are ambiguous I can say so? On a thread all people have to do is click reply and put yes or something more complicated if needed. I am pretty sure all the people I have picked are sure they have CFS. That is good enough for me because if there are several sorts of ME there will be no 'correct' definition of CFS other than being ill enough with fairly typical problems to take the trouble to join PR. In other words, if people on PR are people whose illnesses need sorting out then those are the ones I am interested in.

We have some threads (such as the hugely popular one about resistant starch) that have attracted a proportion of people interested purely in gut dysbiosis or certain polymorphisms related to autism and so on, who are clear that they don't have ME and have never thought that they did but are here to discuss those very specific topics because PR has high-quality discussion and good forum moderation. They don't always discuss their diagnosis, though, which makes it hard to spot that they're not PWME.

But I see you've broken down the question on the thread that you've started so there's no problem.

 

[NK17]

@Jonathan Edwards et al. (all PR members that are active and discussing how to set up a meaningful poll on thyroid issues), I have a question for you that might sound stupid.

What about labs results of young close blood relatives? Can those count for the poll?

In the specific case I'm talking about a young person who has been seen by Dr. Kogelnik and is kept under strict surveillance for possible ME development. In the blood workup there are some thyroid antibodies, which have been and are completely ignored by the pediatrician.

I hope I've made myself clear .

 

[Jonathan Edwards]

@Jonathan Edwards et al. (all PR members that are active and discussing how to set up a meaningful poll on thyroid issues), I have a question for you that might sound stupid.

What about labs results of young close blood relatives? Can those count for the poll?

In the specific case I'm talking about a young person who has been seen by Dr. Kogelnik and is kept under strict surveillance for possible ME development. In the blood workup there are some thyroid antibodies, which have been and are completely ignored by the pediatrician.

I hope I've made myself clear .

I have assumed that my 100 names 'represent' 100PWME. I realise that this might be a little complicated. You might, NK17, want to send me an answer by private conversation. In fact if a few people sent me answers by conversation to begin with nobody could work out the status of anybody who did not post on the thread by a process of elimination. Even though most people here are under pseudonyms I am keen to be doubly sure of anonymity where it might really matter. I will try and clarify the new thread.

 

[Leopardtail]

Exactly what I thought Sasha. So, I have discovered this morning that almost exactly 100 people post regularly. I have excluded two people who probably posted just recently in response to my inventing 'ME4' in this thread (both would be yes, but the idea is to get the right answer, not the one we want).

My question would be a very simple one because this is intended just as a raw look see and if a look see gets complicated it bellyflops. I think it is:

'Are you aware that you have a diagnosis of CFS/ME and have had blood tests that either show thyroid autoantibodies or an under- or over- active thyroid based on T3, T4 or TSH levels?'

On this basis I already know of 4 yes answers. I am fairly sure there are more, although I have no idea how many. Up to 10 would be fairly unremarkable. 10-20 would suggest there may be something to it. More than 20 would be pretty impressive.

The question then would be how to get answers from the 100 posters without causing any offence or concern. I have the list of names - which is hardly confidential since it is just the people who have posted recently. I could post that on this thread or a new one. How people wanted to answer could be optional. I can of course take answers as 'Conversations'. I have not thought through all the issues but I have a feeling it is probably about as simple as that. If a lot of people simply don't think they have ever been tested for either then it would be useful to know that if yes responses are unremarkable. To begin with it might just be interesting to know how many people would answer yes.

Surely be excluding them rather than just taking the most frequent 100 posters we skew the figures. If for example we assume 20% suffer thyroid issues that would be a 10% error in our results.

 

[Leopardtail]

Lucinda Bateman's slides did include this :
Source not given.

She has two obvious grounds for that:

1. T3 stimulates ATP synthase - a problem there would cause similar issues.
2. Many people with ME have multiple hormone deficiencies, that can cause the pituitary to deliberately suppress releasing hormones such as TSH.

 

[Jonathan Edwards]

Surely be excluding them rather than just taking the most frequent 100 posters we skew the figures. If for example we assume 20% suffer thyroid issues that would be a 10% error in our results.

I think I have to make a judgment on the least bad option. These two people had not posted recently until they specifically made comments in response to my discussion of the role of thyroid issues. That to me looks pretty much like a source of bias. If I add them in there is a significant chance of getting an overestimate when in fact there is nothing to find. If I take them out and there really is a significantly raised rate of thyroid problems it should not sink the ship. If throwing out results it is always better to throw out results you would like to keep in rather than ones that you want to throw out! If a real effect does not survive throwing out a few nice results it is not a very exciting effect. And sadly, 90% of scientific papers are reports of non-effects that result from throwing out the results people want to throw out!

 

[MeSci]

I've been in a rush lately so sorry if this is a silly question, but I can't remember how the thyroid questions arose here. Has anyone searched for existing research papers on ME/CFS and thyroid function?

In case not, I just did a partial search of the ME Research UK database and found this 2008 paper. There may be others.

 

[MeSci]

Is it just the cited thyroid blood tests that are of interest? Not antibodies or ultrasound scans? I developed what looked to both my doctor and myself like a goitre, but my ultrasound scan showed no thyroid enlargement, just enlarged submandibular glands.

 

[Leopardtail]

I've been in a rush lately so sorry if this is a silly question, but I can't remember how the thyroid questions arose here. Has anyone searched for existing research papers on ME/CFS and thyroid function?

In case not, I just did a partial search of the ME Research UK database and found this 2008 paper. There may be others.

Prof Edwards saw something on the prevalence of hypothyroidism in ME and wishes to test the prevalence. It is all within the original scope of the thread.

 

[Seven7]

See phase III
http://www.prohealth.com/library/showarticle.cfm?libid=8858
http://drmyhill.co.uk/wiki/Hypothyroidism_-_A_Common_Hormonal_Problem_in_CFS
............................

 

[Jonathan Edwards]

Is it just the cited thyroid blood tests that are of interest? Not antibodies or ultrasound scans? I developed what looked to both my doctor and myself like a goitre, but my ultrasound scan showed no thyroid enlargement, just enlarged submandibular glands.

Sorry MeSci, I missed that query. Can you say if you had positive antibody tests or abnormal hormone levels - I think you have mentioned in the past but I have lost the details.

 

[MeSci]

Sorry MeSci, I missed that query. Can you say if you had positive antibody tests or abnormal hormone levels - I think you have mentioned in the past but I have lost the details.

I haven't been tested for antibodies, and the doctors have always said that hormone levels were normal. I'd have to dig out my test results to confirm whether they were correct, but I did query it once, asking if they had done all the relevant hormone tests, and I think they had.

Someone else said that they had antibodies - in this thread, I think.

 

[voner]

Hey all, There are a couple other items that I learned in that PPT presentation by Dr. Lucinda Bateman that I cited. One was this statement:

...
 75 immune factors examined, and one,
Leptin, correlated with fatigue.

Leptin is a pro-inflammatory agent that
reduces the threshold for microglia in the
brain to activate; i.e., they become more
sensitive to negative events in the body

This is the first explanation for the elevated levels of Leptin that I thought made sense, adding some credence to the thought of neuroinflammation being involved....

Does anyone have any speculation correlating microglia activity and autoimmunity?

I did find this review paper on MS and microglia....

Role of Microglia in CNS Autoimmunity

http://www.hindawi.com/journals/jir/2013/208093/

///////////////////

ps. I thought I also should point out for at least Dr. Edwards sake, and others that are new to this forum that Dr. Bateman is a very astute source. She is one of the clinical docs who has devoted her practice to treating ME/CFS and FMS patients. She's personally invested and has seen thousands of patients. She serves as a patient sample source for many of the recent ME/CFS studies done and she also is a clinical trial location for many studies also. Etc. etc.

 

[Leopardtail]

Hey all, There are a couple other items that I learned in that PPT presentation by Dr. Lucinda Bateman that I cited. One was this statement:

...
 75 immune factors examined, and one,
Leptin, correlated with fatigue.

Leptin is a pro-inflammatory agent that
reduces the threshold for microglia in the
brain to activate; i.e., they become more
sensitive to negative events in the body

This is the first explanation for the elevated levels of Leptin that I thought made sense, adding some credence to the thought of neuroinflammation being involved....

Does anyone have any speculation correlating microglia activity and autoimmunity?

I did find this review paper on MS and microglia....

Role of Microglia in CNS Autoimmunity

http://www.hindawi.com/journals/jir/2013/208093/

///////////////////

ps. I thought I also should point out for at least Dr. Edwards sake, and others that are new to this forum that Dr. Bateman is a very astute source. She is one of the clinical docs who has devoted her practice to treating ME/CFS and FMS patients. She's personally invested and has seen thousands of patients. She serves as a patient sample source for many of the recent ME/CFS studies done and she also is a clinical trial location for many studies also. Etc. etc.

A couple of obvious thoughts spring to mind. First Leptin is fairly new to science hence it's not the most solid field to draw firm conclusions on, though it has generated a lot of excitement. It plays a role in energy management - in that it's produced when fat is formed. In practice that could (in theory) mean that disruption to insulin, cortisol, adrenalin (aka epinephrine), or testosterone could all alter its production due to their direct and indirect effects on lipid (fat) metabolism. It's definitely a useful clue to the larger picture, and I don't know enough immunology to (dis)agree with Dr Bateman's hypothesis but am mindful it's not easy to interpret.

 

[Hip]

@Jonathan Edwards

IL-1β and TNF-α Linked to Precipitating Autoimmunity in Coxsackievirus B Myocarditis

I don't know if this is relevant, but this study found that in a model of coxsackievirus B autoimmune myocarditis:

"the determination of whether to progress from a contained viral myocarditis to a pathogenic autoimmune response is made within hours after induction of infection and is characterized by production of a few key cytokines, including IL-1beta and TNFalpha".

And this study found that inoculating mice resistant to virally-induced autoimmune heart disease with IL-1β and TNF-α alongside the viral inoculation then made them susceptible.

John Chia (and others) have shown that coxsackievirus B is strongly associated with ME/CFS, so perhaps how these viruses behave in myocarditis could give insight into the pathological and autoimmune mechanisms they may trigger in ME/CFS.

 

[Jonathan Edwards]

Thanks Hip. The problem with 'models of autoimmunity' in mice is that they are not in fact models of human autoimmunity. For nearly all human autoimmune diseases there is no evidence for an infective trigger. People confuse autoimmunity with post-infective hypersensitivity responses as in rheumatic fever, Reiter's syndrome, coxsackie infections etc. In none of these do you get any evidence of persistent reaction against self antigens. Unfortunately, for decades lab scientists have worked on these self-fulfilling model systems that don't really tell us anything. Coxsackie sensitivity in mice may tell us about coxsackie sensitivity in humans but that is not related to autoimmune disease as far as we know. 'Autoimmune' gets used just to mean 'excessive inflammation'. Back in the 1950s all the infectious disease doctors looking after rheumatic fever had to find a new job because of penicillin. They all became 'immunologists' and as a result it became fashionable to think that autoimmune diseases were like rheumatic fever, but there is nothing in common as far as I can see. Everybody came to believe in the theory of 'molecular mimicry' but virtually nothing has been found to support that idea.

That is not to say that post-infective hypersensitivity may not be one sort of ME. I am suggesting that in ME2. But ME2 is not intended to be autoimmune.

Looking back I see that Dr Bateman cites potential environmental triggers in autoimmunity as:
virus, bacteria, stress, food, pollutants, hormones
but the list for which we have any evidence is actually very limited. Smoking makes RA more likely. Drugs can induce SLE. Bone marrow transplantation can trigger several autoimmune diseases. That's about it. No viruses or bacteria with the possible excpetion of Guillain Barre neuropathy and that is rather an odd monophasic disease that may turn out to be a post-infective hypersensitivity after all.

 

[Bob]

@Jonathan Edwards
A question re hypothetical models of illness.
If my gut lining were damaged, or inflamed, such that it couldn't heal.
i.e. I developed a leaky gut, and gut flora were seeping into the gut epithelium and into the blood.
And this caused a chronic immune response against the contents of the gut (i.e. food waste, viruses, bacteria, fungi etc.)
Would this fit into one of your models of illness?
And would it make any sense in terms of successful treatment with Rituximab?

 

[deleder2k]

Hello, @Bob. Interesting question. Check this out:

https://translate.google.no/transla...g/pilotstudie-pa-rituximab-og-ibs/&edit-text=

 

[Jonathan Edwards]

Dear Bob,
I think it is important to consider the way the immune system works in detail. It is easy to assume that an immune response would produce inflammation. However, it is worth remembering that the normal function of an immune response is to make one immune - that is to say to show NO inflammation when the stimulus is present.

The immune response in the gut works in a completely different way from that in other tissues. The gut is normally exposed to kilograms of foreign material and its job is to completely ignore it in terms of inflammatory response. A milligram of foreign material in a tissue like kidney, however, would produce an inflammatory reaction. Within the gut there are masses of plasma cells making antibody. If these recognise rubbish in the gut lumen the result is not inflammation but better tidying away of any rubbish that gets into the gut lining. And if we build up antibodies to food and gut bacterial antigens those antibodies will also help to make sure that any material that does get into the blood stream from the gut is very rapidly recognised and phagocytosed - probably in the spleen. The spleen does not get inflamed either when it eats up rubbish like this because its job is to eat up rubbish without complaining.

So when building ideas about how the immune system works one has to take into account the routes involved. An interesting example is the popular puzzle as to why a mother does not reject a baby in the womb as a 'foreign graft'. The answer is that because the baby has a completely separate circulation the mother's immune cells cannot do any harm once in the baby's tissues - they are a bit like a bunch of unarmed pirates in Times Square, not much chance of taking over the USA!

Leaking of the gut certainly occurs in serious bowel disease where there is ischaemia or some other serious damage to gut lining. Bacteria also get into the bloodstream in small numbers when we clean our teeth. But I doubt that bacteria get into the bloodstream on a regular basis and cause any reaction in MEs. The reaction to bacteria is largely due to the innate response to the surface lipopolysaccharide. As indicated, the more of an adaptive immune response there is on top of that the less trouble the bacteria should cause because they will get phagocytosed before any danger signals can be sent out. So conceivably leaky gut could cause someone to be chronically unwell but an immune response would tend to make that LESS likely. And if rituximab reduced antibody levels (which it probably would not in fact but might) it would make things worse I think.

The difficulty for me with all these popular theories is that they do not attend to sufficient detail to get the right predictions. I think we need to put together theories that take into account the complexity of the system.

Best wishes