Do MEs cause CFS?

[Leopardtail]

I wonder if this thread is relevant. It's about people feeling better when they have hay fever and other allergic reactions. In my own case, as my ME improved I reacquired an allergy to wool that had been absent for years. I saw it as a good sign!

Not so good if it's something really nasty like psoriasis though.

I had a similar 'loss' of hay fever when the ME was severe. My gut hunch being the immune stem was too energy deprived to react.

 

[Leopardtail]

It is all rather complicated but you might find our 1999 Immunology article gives an idea of the general mechanism. It is called 'Do self-perpetuating B lymphocytes drive human autoimmune disease?' If you look up the ResearchGate website and type my name in hopefully you will pull up my RG page which has that and some other papers available at a click. You might have to sign up to RG to get that but I hope not.

you have to sign up to researchgate to access any full paper, which they only allow if you are in a qualifying institution, or have published research (in Britain).

 

[Leopardtail]

We must be in different subgroups then! I have had fewer respiratory infections since becoming ill, and the only change is that is has gone from very few to none. Like others, I felt much better when I appeared to have a proper cold or flu.

The only possible infections I can recall since getting ME have been in the ears and/or urinary tract, other than gut problems that might be better described as dysbiosis than infection.

One thing I previously noticed was an upward shunt in blood sugars (due to interferon stimulation of CRH) but few other symptoms except tiredness. Antibiotics produced improvements giving stronger evidence. As my ME improved and my immune system resurrected, I then got symptoms, not surprising since it causes most infective symptoms.

 

[Leopardtail]

Here is the abstract if anyone wants to read: http://www.ncbi.nlm.nih.gov/pubmed/25111603 Can't say I understand much. Does it mean that taking B12 supplements could affect the way the B-cells work? Meaning that B12 works on about the same mechanism (but in a different way, of course, I'm trying to put it simply so I understand myself) as rituximab?

B12 did wonders for me for years. When it stopped working (still don't know why) I went from working full time to more or less bed ridden, as I was before B12. Methylation is one of the reasons people have warned me I shouldn't be taking MTX.

Ninan,

Genes are not only our 'genetic blueprint' they are effectively switches than turn every function on and off (e.g. making a new instance of an enzyme). Methylation is used to activate and de-activate genes. In other words to turn functions on and off. If you are deficient in SAM then vast numbers of functions could be partially affected - what effect that would have is harder to predict..

 

[WillowJ]

My idea for ME5 is that what is in overdrive is a part of the response to virus that does not directly involve the fever mechanism. I am suggesting it involves gamma interferon but not TNF so much. Could well be wrong but that is the sort of angle. It might possibly 'pre-empt' viral symptoms by getting to work on the virus before there is a big enough burst of viraemia (virus in the blood) to trigger the usual fever signals. There might be a distant analogy here with the B27 class I allele. People with B27 get ankylosing spondylitis and Reiter's but I gather that they are the slowest to progress to AIDS if they are infected with HIV. This has led to the idea that B27 is an 'overenthusiastic' class I type.

Interesting; thank you. I had been searching to try to figure out what immune molecule(s) caused fever (so I could search the ME/CFS papers and see if it was featured there), and I hadn't yet found a page that explained.

Overinflammation makes a lot of sense, given how i feel and what medications help (out of what I've tried). Also it seems supported in the literature, but of course we need better studies and follow-up studies for almost everything.

Angela Vincent talked at the IiME conference about the ion channel antibodies that cause rare neurological diseases, some of which can look a bit like CFS. I would be very happy to put in an ME7 based on autoantibodies to muscle ion channels. I bet there is a disease like that but it might be very rare. And then of course there is the possibility that there is a functional cross talk between immune system and muscle of an unexpected kind. It is worth noting that myasthenia gravis is in a sense both a disease of muscle and a disease of thymus. It has a unique structural pathology in the thymus (with B cell follicles there) as well as making muscles weak - maybe because acetyl choline receptors are actually important in the thymus too. The body very often uses molecules for two (or more) completely different purposes - like using a screwdriver to open a paint tin.

Autoantibodies could alter gut function without there being anything to see on scoping. In scleroderma the autoantibodies interfere with gut motility so that you get malabsorption from bacterial overgrowth in the small bowel. The antibodies in Sjogren's affect the mucus glands and I am not sure there is anything to see in that situation either. Anything seems to be possible.

You find new autoantibodies either by luck (most of the early ones) or by intelligent searching with new techniques. That is how the new neurological autoantibodies have been found. People are looking with new methods for ME antibodies and they may be lucky. But there could easily be antibodies that nobody has yet thought of a way to demonstrate yet because there are so many aspects to antibody binding. For instance in RA we now know that anti-CCP antibodies do not recognise any particular antigen. They recognise any protein that has had an arginine changed to citrulline. If you do not test for that you get the wrong answer - which is why for a long time people thought wrongly that these were antibodies to keratin because keratin tends to get citrullinated in normal tissues.

Very fascinating and helpful; thanks so much. I went and found Dr. Vallings' conference summary which I had not yet read, and looked at the pertinent parts. I will read all of it eventually!

It's very encouraging to read that people are looking for ME antibodies.

Like someone else said, I wish I could engage more highly with these ideas but my cognition failed.

I just thought I would add the studies I was referring to earlier, in case it was helpful.

Here is Yves Jammes finding M-wave variations in skeletal muscle (also Hsp variations, which a number of others find, but not always the same heat shock proteins--I started to catalog the Hsp findings once but haven't finished; other findings, too):
http://www.ncbi.nlm.nih.gov/pubmed/19457057

And here are Hollingsworth and Newton finding bioenergetic abnormalities in both skeletal and cardiac muscle. I have not seen the full text.
http://www.ncbi.nlm.nih.gov/pubmed/20497461

ETA: this is probably different from what Jammes found, given their other work. /edit

Second thought, I guess cardiac muscle goes with skeletal even though it is involuntary. So I guess I know of no experimental results for smooth muscle weakness.

I don't fully understand either of these papers/abstracts, but it's clear they are finding, in very small groups of patients anyway, some kind of muscle dysfunction.
They were finding some in the Royal Free outbreak, but I haven't checked to see if the citation from here is on PubMed yet.

 

[Leopardtail]

Interesting; thank you. I had been searching to try to figure out what immune molecule(s) caused fever (so I could search the ME/CFS papers and see if it was featured there), and I hadn't yet found a page that explained.

Overinflammation makes a lot of sense, given how i feel and what medications help (out of what I've tried). Also it seems supported in the literature, but of course we need better studies and follow-up studies for almost everything.



Very fascinating and helpful; thanks so much. I went and found Dr. Vallings' conference summary which I had not yet read, and looked at the pertinent parts. I will read all of it eventually!

It's very encouraging to read that people are looking for ME antibodies.

Like someone else said, I wish I could engage more highly with these ideas but my cognition failed.

I just thought I would add the studies I was referring to earlier, in case it was helpful.

Here is Yves Jammes finding M-wave variations in skeletal muscle (also Hsp variations, which a number of others find, but not always the same heat shock proteins--I started to catalog the Hsp findings once but haven't finished; other findings, too):
http://www.ncbi.nlm.nih.gov/pubmed/19457057

And here are Hollingsworth and Newton finding bioenergetic abnormalities in both skeletal and cardiac muscle. I have not seen the full text.
http://www.ncbi.nlm.nih.gov/pubmed/20497461

Second thought, I guess cardiac muscle goes with skeletal even though it is involuntary. So I guess I know of no experimental results for smooth muscle weakness.

I don't fully understand either of these papers/abstracts, but it's clear they are finding, in very small groups of patients anyway, some kind of muscle dysfunction.
They were finding some in the Royal Free outbreak, but I haven't checked to see if the citation from here is on PubMed yet.

There are three types of muscle willow: skeletal, smooth, & cardiac
Because the heart must beat continuously, it requires a muscle type with massive stamina

 

[MeSci]

I've always taken that delay as a sign of some kind of immune activity or inflammation. The time between overexertion and reaction (PEM) is about the same for me as the time between overexertion (lifting something, doing too much garden work) and pain for my dad who has AS.

It differs too: The more I've overdone it, the longer it takes until the crash, and of course, the worse it gets. If I've done a little bit too much I get worse later during the day. If I've done way too much it can take four or five days, or more. During which I feel just fine (well, for having severe ME) or even better than usual. Then I crash, badly. It's tricky that way.

I think (but would have to have a longer look at my health diaries to be sure, and just don't have the time for now) that if I continue to overexert myself over a period of days, the PEM doesn't set in during that time but after I have stopped, so it doesn't follow the start of the overexertion but the cessation of the overexertion. This could perhaps account for the people who think themselves recovered after a treatment that encourages overexertion. Somehow continuing the overexertion keeps the PEM at bay, then CRASH.

But for some, a crash seems to occur during exertion, according to reports I've read here.

My PEM delay also increased during a period of increasing wellness following the commencement of my leaky-gut diet and supplements in 2012, until it had become just about undetectable but I thought I could just about perceive it about a week after exertion. Since then there have been ups and downs, and my pattern is very unclear at the moment. I usually feel pretty well the day after exertion, but start to feel grotty on the evening after exertion or 2 days after exertion, thus about 30-48 hours later, at the moment.

 

[MeSci]

I had a similar 'loss' of hay fever when the ME was severe. My gut hunch being the immune stem was too energy deprived to react.

My preferred theory relates to changes in the predominant immunoglobulin type, which I refer to in the thread that I linked to - in this post.

 

[taniaaust1]

Obvious question here, has anybody considered self administration of IV saline?

Yes I have but if the experienced blood nurses cant get blood from me, how on earth would I insert a the needle into myself and know Ive got it in a vein? I have been pricing up the needed equipment to try to do saline IVs for myself (not cheap) but really have my doubts if I would manage to be able to do it myself. (I have found someone to try to teach me (a lyme person who does her own IVs) but being housebound, I cant get to her place to learn and she's housebound too so she cant get to mine.

But right now my health is at serious risk due to the severity of my low blood volume and of cause Im very affected by this issue too. (I cant even ME crash usually as my POTS hits me way first..so I cant do enough to even trigger the ME off much now).

I just wish the medical profession would get some common sense as its obvious when someone is collapsed so having to be ambulanced to hospital every couple of weeks for an IV, that I should be getting these at home.

anyway, best not to discuss in this thread. Its off topic and I dont wish to be rude to the dr (oh boy I've forgot his name). Message me if you have more to say about it. thanks.

 

[MeSci]

Interesting; thank you. I had been searching to try to figure out what immune molecule(s) caused fever (so I could search the ME/CFS papers and see if it was featured there), and I hadn't yet found a page that explained.

This page may help, for example this definition:

pyrogen [pi´ro-jen]

an agent that causes fever; called also pyretic and pyrectic. adj., adj pyrogen´ic.

endogenous pyrogen a low-molecular-weight protein that is produced by phagocytic leukocytes in response to stimulation by exogenous pyrogens and released into the circulation; it induces fever by acting on the preoptic area of the hypothalamus to raise the set-point of the hypothalamic thermostat. The pyrogen produced by monocytes and macrophages is not identical to that produced by neutrophils and eosinophils; the mononuclear phagocytes also produce a greater amount of pyrogen for a longer period of time than do the polymorphonuclear cells.

exogenous p's fever-producing agents of external origin, e.g., bacterial endotoxins and other microbial products, antigen-antibody complexes, viruses and synthetic polynucleotides, incompatible blood and blood products, and androgen breakdown products such as etiocholanolone; the action is mediated by endogenous pyrogen.

 

[taniaaust1]

I had a similar 'loss' of hay fever when the ME was severe. My gut hunch being the immune stem was too energy deprived to react.

I used to get aweful hayfever too every year at certain time of year. I dont know if its just a coincidence but I no longer get it since i had ME (instead I just get food intollerences, MCS and not long ago had what could of been a life threatening food allergy). So it makes no sense to me why I'd get allergies to other things but loose my hayfever (so I tend to think its just coincidental).

 

[Leopardtail]

I used to get aweful hayfever too every year at certain time of year. I dont know if its just a coincidence but I no longer get it since i had ME (instead I just get food intollerences, MCS and not long ago had what could of been a life threatening food allergy). So it makes no sense to me why I'd get allergies to other things but loose my hayfever (so I tend to think its just coincidental).

<---- is equally confused

 

[Leopardtail]

@Jonathan Edwards you need to watch this and the other three to concretely understand the problems its by the woman who set up the UK training centre for therapists.

 

[Leopardtail]

Interesting; thank you. I had been searching to try to figure out what immune molecule(s) caused fever (so I could search the ME/CFS papers and see if it was featured there), and I hadn't yet found a page that explained.

Overinflammation makes a lot of sense, given how i feel and what medications help (out of what I've tried). Also it seems supported in the literature, but of course we need better studies and follow-up studies for almost everything.



Very fascinating and helpful; thanks so much. I went and found Dr. Vallings' conference summary which I had not yet read, and looked at the pertinent parts. I will read all of it eventually!

It's very encouraging to read that people are looking for ME antibodies.

Like someone else said, I wish I could engage more highly with these ideas but my cognition failed.

I just thought I would add the studies I was referring to earlier, in case it was helpful.

Here is Yves Jammes finding M-wave variations in skeletal muscle (also Hsp variations, which a number of others find, but not always the same heat shock proteins--I started to catalog the Hsp findings once but haven't finished; other findings, too):
http://www.ncbi.nlm.nih.gov/pubmed/19457057

And here are Hollingsworth and Newton finding bioenergetic abnormalities in both skeletal and cardiac muscle. I have not seen the full text.
http://www.ncbi.nlm.nih.gov/pubmed/20497461

Second thought, I guess cardiac muscle goes with skeletal even though it is involuntary. So I guess I know of no experimental results for smooth muscle weakness.

I don't fully understand either of these papers/abstracts, but it's clear they are finding, in very small groups of patients anyway, some kind of muscle dysfunction.
They were finding some in the Royal Free outbreak, but I haven't checked to see if the citation from here is on PubMed yet.

I have been looking into the same issue. I have managed to work out how fever is implemented, but not the full triggering chain nor exactly how the body 'decides' its fever time (meaning the biochemistry, not the functional pattern). It would be interesting to compare notes once I can give it some attention again.

 

[Leopardtail]

My preferred theory relates to changes in the predominant immunoglobulin type, which I refer to in the thread that I linked to - in this post.

I am vaguely aware of the two sets of imbalances widely discussed by medics, but as yet have not been able to find meta-analyses of the issues. I deliberately used the word 'hunch' re energy management due to a suspicion that the th1/th2 imbalance may be fall-out from that issue. The only thing I know with certainty is that when my ME was severe I had weeks or months of infection with few obvious symptoms then felt far less unwell but had far more infective symptoms as recovery began.

In contrast to you I feel like hell when infected, but also suffer less allergic symptoms and am much more at the high fatigue, high weakness, moderate pain end of the spectrum than the high pain, more moderate fatigue end. My much stronger hunch is that each end of that spectrum involves quite different 'energy biochemistry'.

It's such a shame you are unable to do a full publishable meta-analysis of your immune system readings.

 

[MeSci]

@Jonathan Edwards, apologies if you have already commented on this, but @lansbergen has just posted a message in another thread about the 'Cell Danger Response', linking to a scientific paper which is unfamiliar territory to me, and suggests a rather different potential cause for "a broad array of chronic, developmental, autoimmune, and degenerative disorders."

Are you familiar with this concept, and do you have an opinion on it?

 

[Ninan]

I think (but would have to have a longer look at my health diaries to be sure, and just don't have the time for now) that if I continue to overexert myself over a period of days, the PEM doesn't set in during that time but after I have stopped, so it doesn't follow the start of the overexertion but the cessation of the overexertion. This could perhaps account for the people who think themselves recovered after a treatment that encourages overexertion. Somehow continuing the overexertion keeps the PEM at bay, then CRASH.

But for some, a crash seems to occur during exertion, according to reports I've read here.

My PEM delay also increased during a period of increasing wellness following the commencement of my leaky-gut diet and supplements in 2012, until it had become just about undetectable but I thought I could just about perceive it about a week after exertion. Since then there have been ups and downs, and my pattern is very unclear at the moment. I usually feel pretty well the day after exertion, but start to feel grotty on the evening after exertion or 2 days after exertion, thus about 30-48 hours later, at the moment.

It's about the same for me. The crash comes afterwards. If I'm on an adrenaline surge it usually comes when I start relaxing. If I've overdone it a bit and start resting the first thing that happens is that I get a lot worse (which doesn't make lying down more tempting). But if I keep overdoing it long enough the crash strikes anyway. Mid-sentence. Then it gets bad. So when I know I've overdone it, I try to rest as much as possible and let the crash come. The sooner it comes, the quicker I can get better again. If I do, that is. Sometimes I don't.

 

[Leopardtail]

@Jonathan Edwards, apologies if you have already commented on this, but @lansbergen has just posted a message in another thread about the 'Cell Danger Response', linking to a scientific paper which is unfamiliar territory to me, and suggests a rather different potential cause for "a broad array of chronic, developmental, autoimmune, and degenerative disorders."

Are you familiar with this concept, and do you have an opinion on it?

@alex3619 - I thought high levels of adenosine were caused by AMP being deliberately degraded and expelled from cells due to AMP/ADP/ATP being too large to pass through cell walls, other than during cytosis. What's your view on the paper?

 

[Marco]

Yes, I realised that this was what was bothering the back of my mind although I could not put my finger on it at first. A primary problem with the autonomic system would not seem to get the time scale of symptoms right, I guess.

It may not be a primary problem but autonomic/vascular issues that result in reduced blood flow/ischemia in the muscles, brain or both could produce the necessary 'danger signals' required to activate already primed glia in a scenario similar to ME5.

One source gives the following durations of glial activation (which results in 'sickness behaviour') folllowing various types of peripheral immune stimulation :

LPS (bacterial infection analogue) - microglial activation peaks at 8-24 hrs, duration up to several days;

Poly IC (viral infection analaogue) - up to 8 days;

BCG (yep - the vaccine familiar to UK schoolchildren) - possibly up to 3 weeks.

One other mechanism that I'd considered is heat shock proteins. Jammes and others have found attenuated HSP production following exercise in ME/CFS patients. As I understand it HSP production normally peaks at around 48 hrs post exercise (which suggests to me, if they are doing their job properly, that this should coincide with the maximal cellular/oxydative stress). If this repair mechanisms is defective in ME/CFS patients then 48 hrs post exercise might be when you might expect symptoms to peak. Highly speculative but this timescale does fit that described in the International Consensus Primer :

“prolonged recovery period: usually 24 hours, often 48 but can last days, weeks or cause a relapse”

Worth bearing in mind though that PEM can also often follow purely mental exertion which would make the HSP mechanism less likely.

Just some thoughts.

 

[MeSci]

It may not be a primary problem but autonomic/vascular issues that result in reduced blood flow/ischemia in the muscles, brain or both could produce the necessary 'danger signals' required to activate already primed glia in a scenario similar to ME5.

One source gives the following durations of glial activation (which results in 'sickness behaviour') folllowing various types of peripheral immune stimulation :

LPS (bacterial infection analogue) - microglial activation peaks at 8-24 hrs, duration up to several days;

I like this one as it fits in with my preferred theory!

Exertion causes/exacerbates leaky gut.
Leaky gut involves the translocation of LPS, e.g. http://www.prohealth.com/library/showarticle.cfm?libid=14219

Do you have a link to your source?