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Do MEs cause CFS?

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
In simple terms psoriasis and ankylosing spondylitis look to belong to the 'other side' of the immune system. As far as we know they have nothing to do with antibodies or even any sort of specific 'immunity to self' but rather seem to be due to 'T cells being too busy in a non-specific way'. The easiest way to explain the worsening of psoriasis with rituximab is that helper T cells (CD4+) have the option of either talking to macrophages in a local 'cell mediated' response or talking to B cells to 'help' the B cells make antibody. IL-10 seems to push towards the B cell interaction. If there are no B cells the T cells may go and play with the macrophages - which may be exactly what you do not want in psoriasis. The situation for TNF inhibitors like remicade ought to be different. But TNF production tends to produce a 'balancing' IL-10 production so maybe if you block TNF, IL-10 goes to sleep as well and the T cells go off and play with macrophages again. There are probably other ways of explaining this one though.

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. :(
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
The Leptin finding was discussed at the Stanford conference, and I think there is a thread on this here.

Thanks Alex

You don't happen to know if there was a paper or transcript. I don't recall Younger making the connection between leptin and gliosis?

ETA - Its OK Alex. I tracked down his Stanford video and he does, very clearly as his central thesis, link the two. Which is nice!
 
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Jonathan Edwards

"Gibberish"
Messages
5,256
@Jonathan Edwards

On reflection, do you really think that there is a need for a separate mitochondrial subgroup - ME6 ?

Like ME5, my ME6 is a speculation. I have not someone I think specifically has ME6, but there seems to be enough in the way of hints to suggest this might be a subgroup. I would be more or less prepared to bet that there are mitochonrial disorders that nobody has yet recognised that will get diagnosed as CFS if anything, because we know that there are several poorly characterised mitochondrial disorders based on changes in mitochondrial DNA.

As happens in defining subgroups in rheumatic disease we don't, and should not expect, to end up with a set of mutually exclusive pigeon holes. Some categories overlap with others, as in a venn diagram, and some do not overlap. So the whole exercise of numbering 'diseases' is bogus if one is going to be strict about it. But I do think mitochondria deserve a mention of their own.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
[

@Jonathan Edwards . Thank you for a very interesting thread. You might have noticed the huge amount of posts about lowered/blocked methylation , and the need for extra B12 and folate, among people with ME on the forum. Maybe you have thoughts on this issue, also based on your experiences from treating patients with other diseases?[/user]

I don't yet understand the stuff about methylation. Can you direct me to a paper that explains its role in ME?
Similarly, I am not familiar with evidence for B12 or folate metabolism being different.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
Aha! And another Aha! This one paper on methylation from Monday finds hypermethylation of BCL10, which is involved in B cell proliferation, and CD23 (FcER2), which is what Jo Cambridge at UCL has been getting excited about as a marker of reactivating B cells in autoimmunity! It could be a coincidence but it would be quite hard to have a result more in keeping with what we have been discussing with the Norwegians. I am not sure this has anything to do with generalised methylation but it certainly looks interesting. It might be an easier way to identify B cell misbehaviour than just numbers.

And it looks as if there is another important collaborative group producing interesting data on ME biology I had not come across.
 

bertiedog

Senior Member
Messages
1,738
Location
South East England, UK
@Jonathan Edwards

This poll on whether patients get more or fewer colds and flu might interest you. 99 out of 122 members who voted said that they got fewer incidences of colds and flu since their ME/CFS onset.

I have not had a cold or flu in about 10 years.

Sushi
Well I am the complete opposite, I pick up everything going and it makes me very unwell. Last winter I had 8 separate viruses/infections including Norovirus but I do have an explanation for this now having recently tested positive on an LTT Borrelia Immunoblot done through Infectolab Germany. Also I have a co-infection and my immune system is over-reacting to many different viruses so actually I don't even have ME/CFS, I have been wrongly diagnosed for 14 years so perhaps I shouldn't be joining in with the discussion which I am finding fascinating.

By the way @Jonathan Edwards after going on the facebook UK Lyme's site I am not at all convinced that chronic Lyme disease is that rare because practically all of them were originally diagnosed with ME/CFS and new people (often quite young) are appearing daily and getting very little help from the NHS. From the reading I have done it would seem it isn't just deer ticks that carry infection, it can be any biting insect. If only that was accepted by the powers that be we might get some different answers and even some treatment on the NHS!

(I have chosen to go the herbal route with a Lyme literate herbalist in the hope I can rebuild my broken immune system).

One other thing I would like to throw in is that Dr Horowitz in the UK who has written a great book on all things Lyme talks about a multisystems immune dysregulation which not only involves multiple infections, viruses but also heavy metal poisoning, poor detoxification systems, genetic polymorphisms and finally yeasts and molds. His conclusion that all of the above can be involved in illnesses like CFS/ME has come from seeing and testing thousands of patients who indeed test positive for heavy metal poisoning, usually mercury and/or lead, as well as positive for things like borrelia and co-infections and yeast/mold infections so I think these issues are often overlooked when talking about ME/CFS. Indeed mercury and nickel poisoning were the first real abnormalities that I tested positive for and started off this very long journey which began for me in 2000.

Pam
 

Ninan

Senior Member
Messages
523
Aha! And another Aha! This one paper on methylation from Monday finds hypermethylation of BCL10, which is involved in B cell proliferation, and CD23 (FcER2), which is what Jo Cambridge at UCL has been getting excited about as a marker of reactivating B cells in autoimmunity! It could be a coincidence but it would be quite hard to have a result more in keeping with what we have been discussing with the Norwegians. I am not sure this has anything to do with generalised methylation but it certainly looks interesting. It might be an easier way to identify B cell misbehaviour than just numbers.

And it looks as if there is another important collaborative group producing interesting data on ME biology I had not come across.
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.
 
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Jonathan Edwards

"Gibberish"
Messages
5,256
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?

No, I think it just means that CD23 and BCL10 genes are methylated in a normal way during B cell maturation. I don't see anything in this paper suggesting that there is anything wrong with the methylation process or that altering methylation across the board would make sense.
 

Helen

Senior Member
Messages
2,243
I don't yet understand the stuff about methylation. Can you direct me to a paper that explains its role in ME?
Similarly, I am not familiar with evidence for B12 or folate metabolism being different.

I am sorry I am a bit late with my reply but I read that you have found the interesting article that made some of us excited when posted here. Maybe one-carbon metabolism as a synonym of methylation is more familiar.

Late independent researcher Ph.D. Rich Van Konynenburg proposed that ME is caused by , not only has a connection to, a depletion of glutathione due to a blocked methylation. I shouldn´t try to present this further as English isn´t my first language, but I just wanted to introduce his thoughts. The hypothesis hasn´t been proved scientifically yet, but it works for quite a few people with ME . B12/folate protocols are used mainly by some doctors in USA . I think Dr. Sarah Myhill U.K. uses a similar protocol too. Dr. Neil Nathan and Rich Vank made a clinical study that is presented in the seminar below.

This article, I think, is the best presentation of the hypothesis (2007) :
http://phoenixrising.me/treating-cf...gue-syndrome-cfs-by-rich-van-konynenburg-ph-d

In this video recorded seminar he goes into details (2011)
http://iaomt.media.fnf.nu/2/skovde_2011_me_kroniskt_trotthetssyndrom/

There are also slides from the seminar that are possible to follow as a rather complete presentation too
http://iaomt.media.fnf.nu/networks/iaomt/IAOMT_talks_Rich_Van_K._2011__Part_1R.pdf
http://iaomt.media.fnf.nu/networks/iaomt/IAOMT_talks_Rich_Van_K._2011__Part_2.pdf

T
he presented treatment protocol was the actual at that time, October 2011, but was later changed a bit before Rich Vank died 2012.

There is no evidence for B12 and folate metabolism being different to my knowledge -yet. So far there is only an experience by some ME doctors ( e.g in Sweden and USA) that most of their their patients get better from rather big and frequent doses of B12 and folate. The eventual impact of MTHFR polymorphisms are investigated in an ongoing study in USA.

I hope this can give an idea of methylation issues and its , at least connection, to ME. Thank you for reading this, and for your interest in our struggles for diagnose and treatment. It means a lot to us.
 
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snowathlete

Senior Member
Messages
5,374
Location
UK
@Jonathan Edwards - Rich Van Konynenburg was an active member of Phoenix Rising, engaging in lots of interesting discusion on here in much the same way as you now are. I'm sure you would have gotten on well together, and it's a shame you didn't get the chance to discuss things together; unfortunately, much to our great sadness, he passed away, almost two years ago If my terrible memory is doing me any service.
Thankfully a lot of his thoughts are here on the forum still, I think.
 

Sushi

Moderation Resource Albuquerque
Messages
19,935
Location
Albuquerque
@Jonathan Edwards - Rich Van Konynenburg was an active member of Phoenix Rising, engaging in lots of interesting discusion on here in much the same way as you now are. I'm sure you would have gotten on well together, and it's a shame you didn't get the chance to discuss things together; unfortunately, much to our great sadness, he passed away, almost two years ago If my terrible memory is doing me any service.
Thankfully a lot of his thoughts are here on the forum still, I think.

Glutathione and the Methylation Cycle by Rich Von Konynenburg Ph.D gives links to many of his papers.
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
@Jonathan Edwards I'm one of those who's benefited greatly from my 1.5 years on MB12/Mfolate protocol, specifically, what's known here as Freddd's Protocol. It's returned me to the land of the living, tho not to being 'in the world'. I still have severe limits on my physical and mental energy. I've compiled a Guide of what I found to be the most salient points, linked in my signature.

@bertiedog Dietrich Klinghardt speculates that Lyme is (now) congenital and to some degree, endemic, without a vector.
 

Leopardtail

Senior Member
Messages
1,151
Location
England
@Jonathan Edwards,

I'm not sure how to say this respectfully, but I think you may have the cart before the horse. PEM is a defining feature of this illness and autonomic dysfunction in the form of POTS, etc. is prevalent in a very significant subset of patients. I think that if you are trying to discuss possible triggers or causes for this illness, at least some of the causes should taken to account autonomic dysfunction and probably all the causes should take into account PEM. I remember hearing Dr. Suzanne Vernon say that when they did in-depth surveys of CFS patients she was surprised to find how common significant muscular pain was also.

I personally think vascular dysfunction could take into account these three symptoms (PEM, autonomic dysfunction, muscular pain) and also "Fatigue", "brain fog", etc.. then the question is - What are the core causes that would trigger this vascular dysfunction?
many people with ME suffer a delayed reaction with PEM. Exercise today, first feel like hell tomorrow |& after sleep. How would the vascular hypothesis explain that?
 

Leopardtail

Senior Member
Messages
1,151
Location
England
No disrespect taken. No worries, I am very happy to get the cart before the horse and then find out why the horse comes first. I think maybe Alex has it right though - Its a connected spaghetti nest of causal loops. Then again, this could be a cop-out - we do want to know where the spaghetti starts.

I think I was agreeing that PEM needs to be explained by any theory (although I would not want to leave people with non-PEM problems out in the cold just to be tidy). My thought was that a primary vascular tone problem probably would not on its own explain PEM, although it could easily facilitate it. I suspect that people with, say, pure autonomic neuropathy, who get severe vascular tone issues, may not get PEM.

And then maybe we come back to the same question - what causes the vascular dysfunction? I had been thinking about this particular spaghetti loop and had come to think that at least for MEs the problem is unlikely to START in the autonomic nervous system. The reason for this is that we seem to be dealing with a re-setting of some complex regulatory system. The immune system and the brain are complex enough to reset themselves to a new level through confused internal loops. My guess is that the autonomic nervous system is not quite that complicated - it works like the control system on your central heating and is quite complicated but it may not be complicated enough to reprogramme itself - if that makes sense. Somebody else is re-programming it. You might say that hypertension is a resetting of the autonomic system but I am pretty sure that the real causes of hypertension lie outside and that the autonomic system just resets the way it usually does - although in this case unhelpfully. This may be a confused analysis but it is as far as I have got so far!
I saw some very small scale research on this a couple of years ago that tested subjects for vascular function, cardiac function and related nervous activity before and after saline infusion. The abnormalities disappeared with 'restoration of blood volume'. Were the scale large enough that would have given us a clear answer on this one. The other abnormalities were correct compensations to blood volume.
 

Leopardtail

Senior Member
Messages
1,151
Location
England
Dear Alex,
Certainly we should do the science - and that is happening. But you do need to know where to start looking! So hypothetical speculation isn't trivial. In my career it was 90% of the battle in getting a treatment tried and proved. Similarly, Fluge and Mella tried rituximab in ME because of a hypothetical speculation. The sort of dialogue we are having on this thread to me is remarkably reminiscent of the lab meetings we used to have at UC on a Friday afternoon with a couple of bottles of wine - which is where the whole rituximab idea for autoimmunity began. The evidence we needed was already there or easy to find, we just needed to argue through how to make sense of it. And we went through the same sorts of argument about how it could be like this - no it couldn't - yes it could - how come - maybe like this - OK maybe it could - but would n't that mean that we'd find this... and so on. In the end it was like we had done the whole jigsaw but somebody had not noticed we had it the wrong way up for the edge bits.

I agree about the three systems all working together - particularly that hormones sort of cut across the other two with molecules that do things in both.
We tend to see more discussion of endocrine hormones, nervous systems, vasculature and immunity interacting. While the intra-cellular is seen as 'separate'. It's important to remember that what happens in cells causes what happens outside them. Equally external stimuli affect cells. E.g. thyroid follicular cells require iodine & selenium (& more) to produce T3 & T4. T3 via nuclear receptors stimulates ATP production. T4 stimulates a variety of enzymes. There are many circular relationships between the cellular and the 'hormonal'.

Your first point about ME vs Chronic Fatigue Syndrome vs Chronic Fatigue. Each includes the next as symptom but they are very far from synonymous. ME gives us a much clearer target (PEM) for testing the rationality of hypotheses than does Chronic Fatigue Syndrome. ME has a unique symptom , CFS does not.

As for the subtypes: my suspicion (or crackpot theory) is that no person with ME has a single huge dysfunction but at least two smaller ones thus producing a compound effect. This would explain why it's been so hard to pin down, why no treatment is universal, and symptoms vary. My guess despite that is that we will still end up with some common subtypes as per diabetes & thyroid disease.
One obvious challenge here: if there is an inherent mitochondrial problem each cell (and organ by extension) will stress in proportion to its distinct load, the load will then 'ripple out' through the biochemistry. This could make it difficult to separate trigger based phenotypes from those based on inherent physiological weaknesses.

An examples: sublinical cystinosis risks depletion of ATP + Glutathione, sub-optimal mito function lowers supply of ATP, poor T4 to T3 conversion lowers stimulus of ATP production.

That is one physical phenotype with three methods of reducing ATP.

Drinking too much red wine would concentrate free radicals and affect cystine.
Too much sport would stress ATP synthase.
etc etc

So we have two very complex dimensions
#1 mix of minor deficits
#2 mix of behaviours & triggers
 

Leopardtail

Senior Member
Messages
1,151
Location
England
@ Jonathan Edwards I had anti-thyroglobulin antibodies of 19 UI/mL, with normal value being < 4.1 according to the lab. I've heard different opinions on whether this is significant. What do you think?
Also adrenalin below the detection limit in two separate 24 hour urine catecholamine tests, low insulin, reactive hypoglycemia, low FH and FSH.
The reactive hypoglycaemia would indicate that you are likely producing Insulin, hence the lack of it would not be an issue unless you had high blood sugar readings.

LH & FSH are produced in bursts so one reading is not significant unless active sex hormones are low, you are having trouble conceiving or are highly symptomatic. They might also be an issue if hypothyroidism is suspected.

Adrenalin levels are very volatile so that's only interesting because of the reactive hypoglycaemia. I am a medical scientist not a doctor, so this is not 'medical advice' but that would be the test I might want to discuss with a Doctor. How reliable that result is may depend greatly on urine volume.

Hope that helps.
 

Leopardtail

Senior Member
Messages
1,151
Location
England
Thanks Jonathan Edwards for being here and starting up such interesting discussions. (thou I cant figure out in all the groups I fit. I have severe autonomic issues thou with this illness. My orthostatic hypertension is now going up over 190! but I have low BP when laying, I also have severe POTS.. all as part of the ME I have in which I get over 90 different symptoms too. This illness recently caused me to have to be ambulanced to hospital 3 times for a drip in 6 weeks as I collapsed and couldnt get back up (they actually had to give me 2L, 2 bags of saline each time to bring my BP down!. Im going hypertensive in response to low blood volume).

This illness has now started to affect my kidneys due to my low blood volume. (the experienced blood nurse who came to my home to get some blood from me last week, couldnt even get enough blood from me to do 3 small tubed lots of blood tests, she tried from not just my arms but my feet too so has to come back and try again.



I wish they'd study families too. Out of my nannas 5 sons (4 of them are celiacs, one has Aspergers, one has severe systemic mastocytosis), 3 of these sons (my father and uncles) have children with ME/CFS, there are now 4 of us with ME/CFS (all females) as my sister has it now too (its having a 25% hit rate on us and none of us are past mid 40s yet. We all have grown up and live in different states of the country).

With my nannas illnesses, Im certain this illness or genetic suseptability came down from my nanna and not my grandfather as she's got FM, rheumatoid arthritis, ostero arthritis, IBS, lactose intollerance, migraines/headaches, insomina etc. (she hasnt got ME/CFS thou, no post exertional issue)

What is interesting is that there was ME outbreaks here (In Sth Australia in the 1950s) close to where she lived. So did she get something and is a carrier so passed it on two generations later (she didnt have any daughters only sons).
Obvious question here, has anybody considered self administration of IV saline?