Do MEs cause CFS?

[Jonathan Edwards]

So the general idea is that in ME/CFS there is abnormally high cell death related to exertion, and we only feel that the next day when the body has gone through maintenance routine during sleep. That would make sense to me.

Could this also explain reactions that are delayed by more than one day?

Potentially, since the process of repair in muscle for instance takes several days but I admit that late PEM is a puzzling issue.

 

[Jonathan Edwards]

Ok, but does it require some virus ( any ) to be around at the start ?

And by everyday activity amplifying things to seems like flu, are you referring to the symptoms that PWME experience after over exerting themselves and experiencing flu like symptoms the next day or two ?

Whether a virus has to be around at the start or not I think is uncertain. I suspect it does not. So some people will develop symptoms without any obvious initial viral episode.

Yes I am referring to PEM or just in general feeling lousy at the start of another day.

 

[Jonathan Edwards]

@Jonathan Edwards - One of the more clearly defined effects of exercise on the immune system is an increase in complement C4a (the cleaved, inactive part of C4 after it is activated by either C1qr2s2 or via the MBL pathway).

C4a has been found to be elevated very often in ME as well as in "chronic" (post?) lyme syndrome. It's also found in SLE. It is an anaphyotoxin. It also activates mast cells, which have been at times implicated in ME. The idea of mast cell activation logically should lead one to at least consider complement activation.

I have some strong suspicions about involvement of the complement pathways in ME. I think it would be interesting to test ME patients for circulating immune complexes.

C1-Inh deficiency leads to excessive complement activation, including complement C4. One treatment is androgen therapy - so in theory men might be less affected. However, we don't (to the best of my knowledge) see classic hereditary angioedema, which would be expected.

Personally, I do have elevated C4a. Dr. Shoemaker wrote about this a lot, and I think his clinical observations may be correct, but disagree with his (imo) oversimplification of ME as a mold exposure illness. At one point, over a decade ago, a rheum I saw was contemplating a diagnosis of Behcet's, but ultimately didn't think I really fit.

Lots of speculation here of course... just brainstorming.

There are studies on immune complexes in ME but nothing consistent or reliable. Immune complex assays are a minefield and have gone out of favour in most other conditions. But I agree that some proper documentation of complement and immune complex status in ME/CFS would be something one would want as a basic screen for biomarkers. The problem to date is that nobody has addressed this sort of thing systematically and reliably. Hopefully that is one of the things that may come out of the international Biobank collaborations.

 

[Cshell]

I am new here and don't have a strong science background so I don't know if any of this is helpful or not. I have had CFS for 19 years. During a time of high stress right after I had my 2nd child, I suddenly became fatigues and tested positive for active CMV and EBV. A few years later I had speckled pattern ANA and tested negative for lupus. I have had vitiligo on my chest since I was about 10-12 years old. I take thyroid meds (not sure if thyroid problem is Hashimoto's or not). I have had shingles twice and had a horrible case of chicken pox when I was 5. My husband has a great immune system. He is very rarely sick. He always kisses me when I am in the middle of a flare and doesn't have CFS. My daughter accidentally drank after me one time when I was especially fatigued and got mono (confirmed active EBV). Maybe that was coincidental. The psychosomatic arguments are hard to believe. I frequently push myself and crash. I have often pushed myself to where my muscles completely gave out and I fell or dropped things.

 

[Eeyore]

Whether a virus has to be around at the start or not I think is uncertain. I suspect it does not. So some people will develop symptoms without any obvious initial viral episode.

@BurnA (and @Jonathan Edwards )

Dr. Hyde has done extremely thorough diagnostic workups in his patients looking for any other possible causes of ME-like syndromes, and I'd argue his are the most comprehensive in the ME doc community. He's even gone so far as to write a book about misdiagnoses of CFS made in patients who had other issues (he believes in ME but also believes there are many misdiagnoses by lazy docs who make 30 second clinical diagnoses on extremely complex chronic patients).

He has found many cases he believes to be true ME stemming from the Hep B vaccine. For any non-scientists, there is absolutely no way one can become infected from that vaccine. It's not a live vaccine. It's not even a killed vaccine - it's made of recombinant VLPs (viral like particles) - this is a method by which we can make just a piece of the outside part of the virus - none of the genetic material - to create an immune response.

So in these cases patients are getting ME due to a known, non infectious trigger. There are certainly other examples, but this is one that I can think of off the top of my head. While theoretically it could be that the vax is occurring with subclinical viral infection, this would not be expected to occur more than randomly.

There have also been a number of cases of ME attributed to exposure to organophosphate (or possibly organochlorine) pesticides - so again, a non-infectious cause.

And of course, many (about 25%) do not associate anything in particular with the onset - no inciting event or illness. In these cases one could imagine a subclinical infection though - although I believe this unlikely.

 

[Eeyore]

@Cshell - My mother and I both have a similar syndrome. She got it when she was 15 or so and mostly recovered, and I got it in college and did not recover nearly as well. She does have residual symptoms, but no exercise intolerance, and would not call herself an ME (or CFS) patient. She works full time in her mid 60's and regards herself as being in excellent health.

My point is that there is evidence of a genetic link. It tends to run in families. No one has ever caught it from me as far as I can tell, including my dad and sister, girlfriends, roommates in college, coworkers when I was younger, etc. In fact, the only time I've ever even met someone in person with the illness (unless you count mom) has been at an ME convention or the office of an ME doc.

The psychosomatic arguments are nonsense. There is absolutely no reason to believe a high functioning group of people would suddenly stop working, going to school, interacting with life, socializing, etc. and spend their lives going to doctors. This is just bad medicine and bad science from lazy, unimaginative practitioners who would rather stick a label on someone they can't figure out than admit they cannot figure it out.

 

[MeSci]

At one point, over a decade ago, a rheum I saw was contemplating a diagnosis of Behcet's, but ultimately didn't think I really fit.

Someone on another forum was recently diagnosed with Behcet's after decades of misdiagnosis with ME/CFS.

 

[Eeyore]

Well, it's possible. When I was younger, I got a lot of canker sores (aka aphthous ulcers). I was seen by several docs for it. They were definitely not cold sores (still don't have the HSV-1 virus). This would be consistent with Behcet's, but aphthous ulcers are quite common in teenagers. I didn't have anything genital, which is common in Behcet's. I also didn't have elevated systemic inflammatory markers, and the earlier parts of my illness were completely devoid of joint pain and almost entirely neurologic. I didn't have much in the way of eye symptoms early on, although I have developed some now - but only after decades, and there is no loss of visual acuity, but I do have dry eyes now as well as pigment dispersion syndrome (both verified by objective testing by my ophthalmologist).

I don't have the classic Behcet's HLA's either, although I have one that could suggest it (I think it's B51 that is most common, and I don't have that).

If there are subcategories of ME, I strongly suspect I fit into an autoimmune one. Other than the ME, I don't get a lot of routine viruses. Then again, i leave my house about once a week for a short time, so I'm not exposed to much either. I wonder if the observation by my ME doc and other ME docs that we get fewer infections is connected to our generally more housebound lifestyles.

It's possible I'm an atypical presentation of some autoimmune disease, or even an undifferentiated autoimmune disease. I'd be curious to know if "undifferentiated autoimmune diseases" (or autoinflammatory) can remain undifferentiated over many decades. @Jonathan Edwards - care to take a crack at the last question?

 

[Mij]

If there are subcategories of ME, I strongly suspect I fit into an autoimmune one. Other than the ME, I don't get a lot of routine viruses. Then again, i leave my house about once a week for a short time, so I'm not exposed to much either. I wonder if the observation by my ME doc and other ME docs that we get fewer infections is connected to our generally more housebound lifestyles.

It's possible that this may be what your doctor has observed from his patients. But, I am not exposed to many people and don't leave the house often either. I get a good neurological virus approx every 2 years. It can last a few weeks or go on for months.

I'm not coming down with these viruses because of exposure, but instead from a dysfunctional immune system.

 

[Eeyore]

Well, everyone is different. You may be immunologically different or your syndrome may vary from what most of his patients have, or it may be coincidence, or other. Who knows? I haven't seen a controlled study showing whether or not we get more URI's and routine viruses. Personally, I do not seem to. I suspect my immune system is in hyperdrive and cannot calm down.

 

[Cshell]

@Eeyore I kind of assumed something genetic in immune system that kept a virus from being suppressed once you were exposed to it.

 

[Scarecrow]

I wonder if the observation by my ME doc and other ME docs that we get fewer infections is connected to our generally more housebound lifestyles.

There may be some truth to that but it is also a genuine phenomenon.

I was working full time until recently and I've had no colds and only one GI bug in the last five years.

 

[BurnA]

The idea is that once things have got started the immune system is dysregulated by the presence of antibodies that amplify the sort of cytokine or other signal responses that we usually make to viruses. Everyday activity probably stirs these up a little bit and with the antibodies present that could get amplified to seem like full blown 'flu'. So this is hyper-sensitivity of a signalling mechanism facilitated by autoantibody.

As part of an immune response to a virus the system produces antibodies that sensitise the ‘virus alarm system’ tothe extent that even when there is no virus around it may trigger, just with exercise or stress.
Two molecules might be particularly important here: gamma interferon and the immunoglobulin receptor FcRI (CD64) which is used to ‘pre-arm’ phagocytes with antibody even before any foreign pathogens have arrived.

I would suggest that if rituximab works in ME, and not etanercept, it is for the same reason that this applies to
immune thrombocytopenia, myasthenia gravis, Graves' disease and a whole lot of other autoimmune diseases.
These are diseases mediated by autoantibodies but through effector mechanisms that do not trigger
inflammatory cytokine production. So B cells are involved but not TNF. Since the ESR and CRP are normal in ME
one would assume that any autoantibody mediation would similarly not be through inflammatory cytokines.

@Jonathan Edwards my knowledge of the immune system is almost zero so if this doesnt make any sense forgive me but I cant figure out if the last quote above contradicts the top quotes ?

 

[Jonathan Edwards]

@Jonathan Edwards my knowledge of the immune system is almost zero so if this doesnt make any sense forgive me but I cant figure out if the last quote above contradicts the top quotes ?

The key word is inflammatory in the last quote. I admit that I am cutting corners but one has to be briefish. The ME5 suggestion centres around signalling through maybe something like gamma interferon locally that may not in itself generate inflammation in the sense that TNF or IL6 or IL-1 do but may be responsible for flu like symptoms.

 

[Eeyore]

@Jonathan Edwards - During a recent period when I was particularly ill, I did have some markers of inflammation as well as complement activation. C4a elevated. CH50 mildly elevated. However, serum TNF-alpha was undetectable, IL-6 was normal, CRP was normal (all measured at the largest clinical lab in the USA - not a fly by night cash only kind of place, and ordered by very mainstream physicians). I had joint pain and the rheum felt the joints were very "crunchy" (his word) - but neither red nor swollen. Sed rate was ~0 - as is always the case with me. Fibrinogen reduced, d-dimer markedly elevated. Interpretation was consumption coagulopathy resembling "low level DIC" with elevated fibrinolysis (elevated TPA, abnormally reduced PAI-1).

Any thoughts?

 

[Jonathan Edwards]

@Jonathan Edwards - During a recent period when I was particularly ill, I did have some markers of inflammation as well as complement activation. C4a elevated. CH50 mildly elevated. However, serum TNF-alpha was undetectable, IL-6 was normal, CRP was normal (all measured at the largest clinical lab in the USA - not a fly by night cash only kind of place, and ordered by very mainstream physicians). I had joint pain and the rheum felt the joints were very "crunchy" (his word) - but neither red nor swollen. Sed rate was ~0 - as is always the case with me. Fibrinogen reduced, d-dimer markedly elevated. Interpretation was consumption coagulopathy resembling "low level DIC" with elevated fibrinolysis (elevated TPA, abnormally reduced PAI-1).

Any thoughts?

Not really. I am not an expert on coagulopathies but it sounds like consumption. I think I might have to put you down as ME7! (or ME75.6)

 

[Eeyore]

@Jonathan Edwards - I'm honored! =P

A few more findings that may (or may not) be common to a group of us in this cohort -
low serum VEGF
low VO2 Max on cardiopulmonary exercise test. Low anaerobic threshold (AT). In the words of the non-ME specialist pulmonary med doc, deconditioning may explain some of this, but does not explain the sharply reduced VO2 max or the low AT.
One theory that's been floated by some docs is that low VEGF creates low exercise performance by reducing blood and O2 delivery due to impaired vascularization. If you can't deliver O2 you can't use the O2 even if the heart and lungs are fine. Pulmonary doc thought I had entirely normal lungs but suspected viral cardiomyopathy, hemoglobinopathy, or metabolic mitochondrial dysfunction. Also mentioned decoupling of oxygen pulse. DCM ruled out by normal stress echo (no t-wave inversions, no abnormal wall motion, EKG solid). Hemoglobinopathy ruled out by hemoglobin electrophoresis. Ultimately, no one figured it out - but the doctors think something is wrong.

PS - Dr. Jay Goldstein describes a cohort of patients with similar coagulation defects in his CFS patients (as he called it).

 

[MeSci]

I get a good neurological virus approx every 2 years. It can last a few weeks or go on for months.

I'm not coming down with these viruses because of exposure, but instead from a dysfunctional immune system.

How is it diagnosed? I don't understand how you can come down with a virus without exposure, unless you mean the exposure consists of a reactivation of a dormant virus.

 

[Mij]

@MeSci exposure to people or environment ex: flu season.

There are times I have high titres to HHVG and or EBV, and others when I know I have a viral episode. It's been going on for many years. Symptoms include, swollen lymph glands, vertigo, weakness in my legs,. sore throat, inflammed/sore ears etc.

Is this what you are asking?

 

[BurnA]

Continued from the thread: Who tried immunosuppressive treatment/drugs.

The emphasis is on immune regulation errors, because that is what makes sense to me, but everyone can probably think up some other sorts of MEs based on their own experience.

Not that these are based on my experience but there seems to be plenty of people who consider that an ongoing virus infection can play a role. I dont want to put you on the spot, but any opinion on that ?

Also, vaccines are mentioned in certain cases too, could these cause immune regulation errors (and if so how) ?