My Million Dollar Question: Virus or Immune Malfunction?

[PhoenixBurger]

Is this the million dollar question for everyone here?

Its my million dollar question. And as the months go by, and "whatever it is" continues to creep up on me, I get more and more frustrated because I know I could be taking action. But the possible actions are opposites. If its a virus, then I need to strengthen my immune system to fight it. If this whole thing is IRIS / Inflammatory Immune / Autoimmunity of some sort, then the LAST thing I want to do is power-up my immune system even more.

Is there some way to know whether the thing you're experiencing is autoimmune / inflammatory immune in nature versus ..... your immune system actually fighting something important (cancer or virus) ?

How would one know? I have taken countless steps over the last 3 years. And had some very strange results. For example: My CMV igg and igm were sky high when I was in my worst symptoms, yet despite tests showing this immune reaction to CMV ... when we did PCR testing, it came back negative. "No CMV virus found".

Twice.

Same thing for Lyme. Powerful immune markers for "Acute" lyme disease, yet negative Western Blot. Negative PCR. Negative C6 Peptide (the gold standard). Other similar results with other viruses - all showing current, acute and highly active, yet not a single particle found in my blood when we looked for the actual virus. This lead me to believe I had an inflammatory immune syndrome that was over-reacting to past infections.

Dr. Klimas/Rey ran my immune function tests. It showed very hig CD8 and Natural Killer Cell activity ... and she even asked if I was tested for cancers. I was. Absolutely nothing was found. No abnormalities. Nothing on MRI. Nearly all bloodwork normal. So here I was with immune activity out the wazoo .... yet apparently nothing being fought.

So here I sit with continued symptoms, not knowing whether I should be getting my immune system under control, or whether I should be helping it grow stronger.

How do you know if its autoimmunity or a cancer/virus ?

Thanks.

 

[SOC]

First, the immune system is far more complicated than "boosting" or "suppressing" it. You can have parts that are over-reacting and other parts that are under-reacting. If you're going to try to alter your immune reaction, you need to target what is wrong, not globally boost or suppress. And there's always the possibility that the "abnormal" reactions are necessary to deal with something going wrong in your body otherwise, and trying to change those reactions would be dangerous. IMO, immune-altering meds and supplements should only be used under the care of a doctor knowledgeable about the immune system. Drs Klimas/Rey would fall under that category.

Second, high NK cell function AND high CD8 cell number is opposite of what is normally seen in ME/CFS. As I understand it, the immunologists studying ME/CFS see low NK cell function in some patients and low CD8 cell numbers in others. Having both high seems odd in an ME/CFS patient. What are Drs Klimas/Rey saying about it?

From the tiny bit I know, high NK cell function AND high CD8 cell numbers are more indicative of serious active infection or cancer, but I am far from an expert in the field. Perhaps it's a pattern that is seen in early ME/CFS but not yet recognized because we haven't yet studied early patients separately from later patients. Where are you in your ME/CFS journey -- within the first couple of years, or a long-time patient?

 

[halcyon]

The thing to keep in mind is that PCR testing isn't perfect. I've read that even during acute infection certain viruses are very difficult to pick up with PCR. In the chronic case, it's probably a needle in the haystack situation. Or even worse, the needle is buried in the ground underneath the haystack. You're just not going to find it that way.

I think, despite all the downsides, that antibody testing is a good place to start. So you've been tested for CMV and lyme, how about enteroviruses (coxsackie B and echovirus), parvovirus B19, EBV, HHV6, VZV, C. pneumoniae, and Mycoplasma? Boosting immune function may not be enough to fight these things. You need to try to figure out which infections are active and go after them with targeted antivirals or abx where available.

I've not had my NK cell function tested, but I do also have elevated CD8 counts. I have highly elevated antibody titers to echovirus, and a stomach biopsy that tested positive for virus to back it up.

 

[SOC]

@halcyon,
Is my memory correct (now there's some wishful thinking ) that PCR testing would not detect tissue-based, rather than blood-based infections because the amount of viral material in the blood could be very low in tissue-based infections? Also, is it true that the accuracy of PCR testing depends on whether they test whole blood or some part of the blood -- one way being better for some infections and the other for different infections?

 

[halcyon]

@halcyon,
Is my memory correct (now there's some wishful thinking ) that PCR testing would not detect tissue-based, rather than blood-based infections because the amount of viral material in the blood could be very low in tissue-based infections? Also, is it true that the accuracy of PCR testing depends on whether they test whole blood or some part of the blood -- one way being better for some infections and the other for different infections?

Yes, that seems to be the case. The number of viral copies in the blood is so low that it borders on undetectable. Dr. Chia spent a lot of time playing around with PCR looking for enteroviruses. What he found was low copy numbers present, finicky assays where you had to get the primers just right to get a positive, and after all that he found that patients tested over time would fluctuate between positive and negative. Samples for PCR also have to be handled very quickly and carefully. I'm not sure about your second question, but that wouldn't surprise me. If you only tested serum, you might miss infected leukocytes for example.

 

[justy]

I also have High NK function - but negative Lyme, but I do have Bartonella and Cpn - have you been tested for co infections? Like SOC said its complex - I have both under active and over active immune markers.

 

[wastwater]

Simian CMV is something I find interesting.

 

[Hanna]

I also have High NK numbers (>25%) with several overactive immune markers and CFS diagnostic from 1998.
Your million dollar question @PhoenixBurger may concern a whole sub-group here.

 

[SOC]

I also have High NK function - but negative Lyme, but I do have Bartonella and Cpn - have you been tested for co infections? Like SOC said its complex - I have both under active and over active immune markers.

I have high-normal to slightly high NK cell function, too, but low CD8 cell numbers. I suppose that's why low NK cell function is not considered a definite biomarker -- many of us don't have low NK cell function. What I find particularly interesting is that even though my daughter and I had the same very sudden onset flu-like illness at the same time and a similar symptom pattern otherwise, she has (had) low NK cell function (and sometimes number) while I have normal/high NK cell function. It's all still a mystery. We need more research.

 

[PhoenixBurger]

Thanks @SOC - yeah this is such a mystery. And I often don't know if I belong here. But you guys are without a doubt the most intelligent, informed people in medicine I've ever interacted with. And that includes all my doctors. They may be smarter, but they rarely communicate or invest much time. Which renders their knowledge somewhat useless to me.

Rey basically gave me 1 liners, and left me to figure out the rest. I did not feel like I had much clear communication from her, and that may be because she wasn't sure what to make of the numbers she saw. She suggested Valcyte to address the CMV, but I was just finished taking AZT and other antivirals associated with cancer risk, which are what got me in this situation in the first place (Post exposure prophylaxis). So the last thing I needed to be doing was taking another drug associated with Cancer. Yes I know - most people here feel its not an issue.

Plus, with a negative CMV PCR twice, I wasn't sure what to think. I have researched the possibility of false negatives with CMV PCR and its simply unheard-of. It doesnt exist. You definitely hear about false negatives with other tests. But for example, HIV PCR is never wrong. And nobody could confirm that CMV PCR is ever wrong either. Especially in the presence of a high IGM (current/acute/active). They rely on it heavily for pregnant women as well.

More importantly, doctor after doctor after doctor told me CMV does not cause all these problems I was having. (months of neuropathy, neuromuscular symptoms, nerve pain, severe fatigue, chills, crawling sensations, spine pain, migraines). Most of this resolved with exercise and eliminating gluten (!!!).

Explain that one to me.

Today my picture is a bit different. I get inflammatory symptoms all over when I am run down. Skin issues. Mucoseles. Chalazions. Inflamed lungs. GERD. Lupus-like mask (very mild, derm said it was rosacea) etc. Inflamed armpits, groin, and neck in the glands area, but I don't feel any large swollen glands. It just aches and burns.

Its all so non-specific that it reminds me of people who ultimately ended up with autoimmune diagnoses.

The most upsetting element is this impossible-to-describe sensation. If I do not exercise, after several days, something begins to "build up" inside me and my whole body feels like it is getting very very sick. I can't even describe the sensation. I get inflamed glands (but they dont swell) ... inflamed armpits, inflamed groin tendons (again no ability to feel swollen glands) inflamed lungs .... fatigue. Skin issues.

But I get worse and worse ... until .... I go to the gym and lift weights. ?!? It doesn't make any sense. I must flex my muscles, and I must run on the treadmill and get my lungs inhaling deep ... then this inflammatory monster just "drops off" and becomes subdued. For at least 3-4 days. Then it starts to creep back.

As long as I get good sleep, consistently work out, and avoid gluten, sugar, and stimulants, I can bring myself almost to the point of 100% recovery.

I guess its great that im being forced to eat right and exercise, but it really scares me that whatever this is comes on like a freight train if I stop. My continued increased lymphs and WBC is also a concern as it seems to be steadily rising. Just now past the top limit. Nothing crazy.

I don't know. I can't even communicate to a doctor whats wrong in the 30 second "speed recap" im forced to do when I first see a doctor. Im sure I sound like a complete idiot, and im sure they think im a hypochondriac. But something inside me is happening. Maybe its just the CMV. I know that virus saturates every cell in your body and infects it .... but man this has been 3 years, and whole-body insanity.

 

[Ema]

It's my million dollar question too...I also have high NK cells, high CD8 cells (and CD4 cells) and according to the cytokine profile I just did, elevated cytokines up the wazoo including interferon gamma and all the rest.

So am I fighting an infection or has my system just gone bananas? I'd really like to know too!

 

[Mij]

What about the CD4 CD8 ratio? Mine is increased which indicates a possible autoimmune disease (?) and yet those with viral infections have low ratio. I think aging might decrease it too.

 

[SOC]

What about the CD4 CD8 ratio? Mine is increased which indicates a possible autoimmune disease (?) and yet those with viral infections have low ratio. I think aging might decrease it too.

My CD4:CD8 ratio is high too, but it's because I have low CD8 cell numbers. One could also have a high ratio from having high CD4 numbers, which may be an entirely different issue. I think the ratio, rather than absolute numbers, is really only relevant in HIV, but I really don't know for sure. It's all so complicated.

 

[Mij]

My CD4:CD8 ratio is high too, but it's because I have low CD8 cell numbers. One could also have a high ratio from having high CD4 numbers, which may be an entirely different issue. I think the ratio, rather than absolute numbers, is really only relevant in HIV, but I really don't know for sure. It's all so complicated.

My CD8, CD4 and all my other lymphocytes are below normal. I don't know my NK function numbers though.

I wanted to add that how we are feeling doesn't necessarily reflect these numbers either. My numbers and ratios were normal range when I was at my sickest. They became abnormal over the years . . . so it seems it's more of an immune system dysfunction.

Let's raise it to the "two milliion dollar question" thread.

 

[Stretched]

<<But I get worse and worse ... until .... I go to the gym and lift weights. ?!? It doesn't make any sense. I must flex my muscles, and I must run on the treadmill and get my lungs inhaling deep ... then this inflammatory monster just "drops off" and becomes subdued. For at least 3-4 days. Then it starts to creep back.

As long as I get good sleep, consistently work out, and avoid gluten, sugar, and stimulants, I can bring myself almost to the point of 100% recovery.>>

I'll defer on the cellular biology and offer a practical alternative to scientificating your malaise into CFS. I know you
want a solution as each of us does.

From my perspective what you describe seems to be an anomaly to ME/CFS/SEID...that excersise
and good sleep (?) ward off the gremlins for a few days. 'Good sleep' and hard exercise is almost unheard of
with CFS and PWC's.

Prior to the onset of my own CFS affliction I was a 'lay athlete' - jogging 3 times a week, lifting weights every other day, bicycling, et al. trying to ward off the stressors of a very demanding lifestyle. After onset the ability to do any of those things left very rapidly. It soon got to the point that if I did a set of push ups I went down for a week.

That was about 30 years ago. I tried the push-through-anyway approach and got worse, progressively. This pattern seems to be the theme with most PWC's. Your described routine leads me to question if you actually fall under the umbrella of CFS?

You could be prolonging your suffering when you might discover you have some other affliction, whether viral, autoimmue or other. Maybe you would find some relief in seeing an immunologist outside the CFS school.

In hindsight, if I experienced what you have described (again), I would take a leave and rest until the cows came home and take ani-virals for a year. There are otherwise many independent places where you can test for every medical condition (under guidance and interpretation) as long as your wallet holds up.

 

[unto]

I am personally convinced that the cause of ME
be a virus (or other pathogen) unknown (as the dr. W. John Martin), this virus (in some cases) can always be active and then infect.
For twelve years, in some forums-cfs Italian, I speak of this belief;
everything is the result of my experience of 30 years of ME / CFS ......; after the first few years, slowly, I realized (with anguish) that some people closest (family members, relatives, friends, partners) showed the same symptoms, there is one person that I met in 2005 (20 years after the onset of ME in my body) and later
had symptoms of the disease .....

we do not have a autoimmunity but a germ unknown that can live
inside our body

 

[Valentijn]

The most upsetting element is this impossible-to-describe sensation. If I do not exercise, after several days, something begins to "build up" inside me and my whole body feels like it is getting very very sick. I can't even describe the sensation. I get inflamed glands (but they dont swell) ... inflamed armpits, inflamed groin tendons (again no ability to feel swollen glands) inflamed lungs .... fatigue. Skin issues.

But I get worse and worse ... until .... I go to the gym and lift weights. ?!? It doesn't make any sense. I must flex my muscles, and I must run on the treadmill and get my lungs inhaling deep ... then this inflammatory monster just "drops off" and becomes subdued. For at least 3-4 days. Then it starts to creep back.

There's something called "Reflex Neurovascular Dystrophy" which can be associated with various autoimmune disorders (or not). Basically for patients who have it, inflammation issues cause widespread pain by reducing vascular flow and allowing lactate to build up, but regular exercise helps regulate vascular flow and resolve the pain.

Maybe you've got something similar going on?

 

[PhoenixBurger]

There's something called "Reflex Neurovascular Dystrophy" which can be associated with various autoimmune disorders (or not). Basically for patients who have it, inflammation issues cause widespread pain by reducing vascular flow and allowing lactate to build up, but regular exercise helps regulate vascular flow and resolve the pain.

Maybe you've got something similar going on?

The whole lactic acid buildup thing has absolutely crossed my mind several times. Never knew of how it might be working or by what mechanism though. I definitely had muscle burning all over for awhile there and yes - exercise would alleviate it.

But as mentioned, it's all now morphed into other inflammatory displays. Mucoseles. Chalazions. Inflamed lungs. Gerd. Skin manifestations. And the ever present groin/armpit/neck gland aching, without swelling. Even that goes away with exercise (which is anti inflammatory) and eliminating all sugar (which is pro inflammatory).

Keeping in mind my new CMV infection however... CMV seems to wreak havoc all over the body in some people. Heart issues, lung issues, and even brain cancers. It's a system-wide virus that gets deep into the gut and muscle cells the most. So I honestly think this may be my culprit. Dietary changes and exercise are my savior so far.

I truly do appreciate you all being so tolerant of my presence here, as I clearly don't have typical CFS. I just value your input so much because you all know so much. So thank you. I'm in the middle of a "flare" now, and I think I will get the CMV igg/igm checked again. Maybe go on Famvir. I will also read up on that condition you mentioned.

Thank you.

 

[wastwater]

Its a sensible angle,vaccines were contaminated and admitted to by the government with monkey viruses,and simian CMV is a sensible idea.CMV mutates genes

 

[w john martin]

Dear Wastwater,
Thanks for acknowledging SCMV as a viral cause of CFS. Public Health authorities have yet to acknowledge a 1994 article entitled "Cytomegalovirus-related sequences in an atypical cytopathic virus repeatedly isolated from a patient with chronic fatigue syndrome." Am. J. Path. 145: 440-451. This paper was followed by the 1995 report entitled "African green monkey origin of the atypical cytopathic 'stealth' virus isolated from a patient with chronic fatigue syndrome." Clin. Diag. Virol. 4: 93-103. Avoiding the issue of monkey cytomegalovirus contamination of polio vaccines has helped delay consideration of the possible origin of HIV from chimpanzees used in the testing of experimental polio vaccines. This issue has now been formally presented in an article entitled “Chimpanzees inoculated with cytomegalovirus contaminated polio vaccines may explain origin of HIV-1” published in the Journal of Human Virology & Retrovirology 2(2): 35, 2015.