Do MEs cause CFS?

[Jonathan Edwards]

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) ?

I find it hard to believe that ongoing viruses are causing a disease of this severity without there being clearer evidence. I may be wrong but I think persistent infection is unlikely to be relevant. Virus have always been blamed for things we do not understand.

ME seems to be different from most autoimmune disease in that it does look as if infection may be a trigger in some cases - particularly epidemic cases. That would be similar to reactive arthritis which is an immune dysregulation but not autoimmune. If infection can trigger then vaccine probably can. But we do not have any clear idea how the immune dysregulation of reactive arthritis arises from an infective trigger. It looks like some sort of persistent T cell activation but that is about all we know.

 

[MeSci]

@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?

So you sometimes have high antibody titres? That could mean that aspects of the immune system are sometimes overactive, couldn't it, @Jonathan Edwards, rather than amounts of virus being increased?

The symptoms you list are for me just ME/PEM symptoms. I used to think that they indicated infection, until I finally made the connection with overexertion. With some people they appear more commonly with stress. I also get them when my gut is misbehaving, sometimes due to dietary error or a supplement that doesn't suit me.

I tend to think that I do have immune overactivity, this being consistent with the fact that I - and many others - tend to feel better in the evenings, when I think we tend to have higher cortisol response - the reverse of people without ME. The cortisol damps down some immune activity.

I'm probably not expressing this very well due to fuzzy-brain syndrome - I'm sure Prof Edwards can do much better!

 

[Jonathan Edwards]

So you sometimes have high antibody titres? That could mean that aspects of the immune system are sometimes overactive, couldn't it, @Jonathan Edwards, rather than amounts of virus being increased?

The symptoms you list are for me just ME/PEM symptoms. I used to think that they indicated infection, until I finally made the connection with overexertion. With some people they appear more commonly with stress. I also get them when my gut is misbehaving, sometimes due to dietary error or a supplement that doesn't suit me.

I tend to think that I do have immune overactivity, this being consistent with the fact that I - and many others - tend to feel better in the evenings, when I think we tend to have higher cortisol response - the reverse of people without ME. The cortisol damps down some immune activity.

I'm probably not expressing this very well due to fuzzy-brain syndrome - I'm sure Prof Edwards can do much better!

Rises in anti-viral titres can be 'anamnestic', which means that whenever there is a non-specific stimulus to the immune system you can get rises in antibody levels to microbes you have seen in the past.

 

[MeSci]

Rises in anti-viral titres can be 'anamnestic', which means that whenever there is a non-specific stimulus to the immune system you can get rises in antibody levels to microbes you have seen in the past.

Thanks! And I meant to say that symptoms are often due to immune activity rather than to actual infection, the common cold being a prime example.

 

[Mij]

@MeSci My viral episodes for the most part flare up in April, which is when allergy season starts. So my immune system is over activated or over stimulated?

I've had high titers to herpes viruses at times, yes. I don't get tested every time though, so who knows. The symptoms are not PEM in my case although I have had sore throats/tender glands many years ago during PEM.

My WBC dropped to 2.9 a few months ago and I think my lowered immune system is affected from drops in estrogen and menopause. I can not get rid of these viral symptoms I've been having since April

I also feel much better in the evenings.

I'm trying to treat inflammation rather than specific viruses that are here to stay.

 

[Eeyore]

@Mij - There has long been a reported increased frequency of allergy sufferers in the ME patient cohort, so it's entirely possible that there is a connection between allergy season and symptom exacerbation.

I've had a curious phenomenon for many years where I develop lower back pain and mild morning stiffness - even in the absence of other symptoms - during allergy season. I don't know why this might be true but I suspect it is a general inflammatory issue.

 

[Eeyore]

That would be similar to reactive arthritis which is an immune dysregulation but not autoimmune. If infection can trigger then vaccine probably can. But we do not have any clear idea how the immune dysregulation of reactive arthritis arises from an infective trigger. It looks like some sort of persistent T cell activation but that is about all we know.

There are some case reports on vaccinations causing reactive arthritis in the literature. Not big studies, and not that many, so they could be misinterpreted observations, but they do exist. In particular, there seems to be some increased likelihood with BCG vaccine.

 

[Eeyore]

It's important to always remember that increases in viral titers are NOT a measure of the virus itself. They are a measure of the body's response to the virus, and generally denote increased immune protection from that virus. Viral titers are checked after vaccinations sometimes to see whether a person's immune system reacted sufficiently for the vaccine to be effective.

It is possible that an increase in viral titers may suggest a reactivation and hence the immune system is mounting a defense, but this is far from certain.

It is also possible the body saw a related pathogen, or even just something that looks like the pathogen (it could be pollen for all I know - things that are broadly different can sometimes look similar on a very micro level).

Furthermore it's possible for ALL antibody titers to move up or down at the same time due to general immune system activation or lack thereof. Certain circulating cytokines will cause broad upregulation of antibody production, and they can affect B-cells regardless of whether a pathogen is even present.

Finally, there is a great deal of randomness to antibody levels, and most of us have antibodies to all pathogens at some very low level, even those we've never been exposed to. This is why you need a cut-off for a positive result. I had a doc who used to graph all my viral titers for herpes viruses. I test negative for EBV and CMV, yet they too were graphed (this practice doesn't make a lot of sense at all for an uninfected individual). It looked like a complelely random saw-tooth like pattern of varying peaks and valleys. The point is - even though I didn't have a virus, I still had many fold increases and decreases in titers, which meant nothing.

If someone tells me they are reactivating a virus frequently and it is poorly controlled, I'd prefer to see a PCR result, which looks for the actual genetic material of the virus. If this goes up over time, and is correlated with symptoms, you have MUCH better evidence that it could be causally linked.

Also I'm not sure getting viral titers down is a good idea in all cases. These are your protection from viruses. If you drop the titers, you drop your body's highly effective, highly specific defense mechanism. Patients with herpes simplex who take very long courses of valtrex sometimes serorevert (meaning they test negative - even though they still have the virus - but the body stops making antibodies to the virus because the valtrex is preventing the virus from reproducing). When that person comes off the valtrex, they don't have natural antibody protection anymore, the virus reactivates, and they can get bad outbreaks.

So this analysis of viral titers meaning treatment is required needs to be very carefully thought about.

 

[MeSci]

@Mij - There has long been a reported increased frequency of allergy sufferers in the ME patient cohort, so it's entirely possible that there is a connection between allergy season and symptom exacerbation.

I completely lost my allergy to wool for most of the time I've had ME, then when I had some improvement it came back, and I can no longer have wool next to my skin again.

Others have had a similar reverse correlation between allergy and ME severity. See this thread.

 

[MeSci]

If someone tells me they are reactivating a virus frequently and it is poorly controlled, I'd prefer to see a PCR result, which looks for the actual genetic material of the virus. If this goes up over time, and is correlated with symptoms, you have MUCH better evidence that it could be causally linked.

I so wish I could get tests done when I am experiencing symptoms, so that I could make some sense of them and make adjustments. The trouble is - like many of us - when I am particularly ill I can't get to the doctor. Like my first bout of severe hyponatraemia - I was much too ill to get to the doc, and he wouldn't come out to me. So I continued to suffer without diagnosis and incurred permanent bone and tooth damage before being rushed to hospital with another severe attack 3 years later. Not exactly cost-effective for the NHS...

 

[Eeyore]

@MeSci - In Dr. David Bell's recent book, he relates a story of a farmer who has ME. When the farmer got really ill, he'd expose himself to poison ivy - and he'd feel better when he did. I have no idea if it's a general phenomenon, but it may be, and could be interesting.

 

[Eeyore]

I so wish I could get tests done when I am experiencing symptoms, so that I could make some sense of them and make adjustments. The trouble is - like many of us - when I am particularly ill I can't get to the doctor. Like my first bout of severe hyponatraemia - I was much too ill to get to the doc, and he wouldn't come out to me. So I continued to suffer without diagnosis and incurred permanent bone and tooth damage before being rushed to hospital with another severe attack 3 years later. Not exactly cost-effective for the NHS...

Another problem with using titers is delay factor. If you really want to know why you are sick, antibodies aren't a great test at all for something that is relatively new onset or has worsened in the short term. For example, in HIV, you need to wait months before a test is considered negative. The body doesn't just produce high levels of antibodies overnight. It is true that if you have already been exposed, it might increase those levels faster, but not instantly, and it could be delayed enough that you wouldn't get a useful reading from antibody titers anyways.

 

[Mij]

I so wish I could get tests done when I am experiencing symptoms, so that I could make some sense of them and make adjustments. The trouble is - like many of us - when I am particularly ill I can't get to the doctor.

I've had PCR testing done for many viruses when I was highly symptomatic and they all came back negative.

 

[Eeyore]

That strongly suggests that the viruses assayed were not reactivating when you had your symptoms.

 

[Mij]

So what does this mean in that case? Inflammation?

 

[Eeyore]

It's not a conclusive finding. It suggests only that the pathogens you pcr'd were not found, and hence were not likely to be active, at the time of the test. PCR is very sensitive for finding viral DNA/RNA, so if it's negative, it probably means there was nothing to find. So why did you feel lousy? All we've done is rule out one possibility, the possibilities remaining are near infinite.

Yes, it could be inflammation. Inflammation is a more complex concept than it is given credit for. I do not believe you can measure 2-3 serum proteins and conclude whether or not inflammation is present (although I suppose a positive result on some tests virtually assures that it is).

It could be that your immune system is responding for some other reason, due to some other stimulus. We don't have the information to answer that question yet.

When you get a cold, most of the symptoms you experience are not related to tissue damage caused by the cold virus you contract. Instead, the symptoms you experience are related to the immune system becoming active (cytokines, inflammatory mediators, other factors - very complex). Many symptoms that we associate with infection are actually caused by the body's attempt to fight that infection rather than the infection itself.

I do think there is very likely an element of immune dysregulation / dysfunction (not necessarily suppression / deficiency) that causes many of our symptoms, but I'm not sure it's the same for everyone, or what it is.

 

[Eeyore]

@Mij - A key point is that antibody elevation can indicate past or current infection, whereas PCR indicates current infection as it directly measures the virus itself, not the body's (long term) response to a virus.

 

[MeSci]

@Mij - A key point is that antibody elevation can indicate past or current infection, whereas PCR indicates current infection as it directly measures the virus itself, not the body's (long term) response to a virus.

Don't different types of antibody indicate different stages of infection, as described for example here?

 

[Eeyore]

@MeSci - Sort of.

The general rule is that early infection is accompanied initially by a rise in IgM. The time frame for this is pretty variable, but in most cases probably a week or two - that's a very rough estimate. B-cells undego class switching to produce IgG, which is the main circulating antibody that provides long term immunity.

The rules are far from absolute though. In some cases, IgM increases with reactivation, and in some cases it does not. Sometimes IgM is never really detectable, and IgG becomes detectable first.

So you have to be very cautious what conclusions you draw.

IgE is found in much, much lower quantities and is involved in allergic and parasitic responses.

IgA is secreted into the mucosa and other surfaces that are likely to come in contact with pathogens (e.g. the gastro intestinal tract). There is also circulating IgA.

IgD is bound to B cells and functions very differently, and is rarely relevant in diagnosing any disease.

 

[halcyon]

I think it would be interesting to test ME patients for circulating immune complexes.

This has been done and elevated levels of circulating immune complexes have been found. Notably some bound to enteroviral antigen.