Wednesday, January 11, 2012

Immune System Abnormalities in ME/CFS

(NOTE: Many of you expressed interest in hearing more about how Imunovir/inosine has helped me this past year, so I started to write a blog post about that, but I quickly discovered that I needed to explain how ME/CFS affects the immune system before I could explain how inosine treats it. It's just too much for a single post. So, consider this Part 1, and you can read about using inosine as a treatment here. It's been very effective for my son and I.)

My Story
Within the first year of getting sick, before I even had a diagnosis, I knew that some sort of immune system problem was at the heart of whatever this mystery illness was. I saw the same pattern, over and over again, with recurring symptoms like sore throat, flu-like aches, and congestion, but it was obvious these weren't colds - the symptom pattern was exactly the same every time, signaling the start of another relapse (you learn to instinctively call them crashes pretty early - it's the perfect description). One Infectious Disease doctor told me I was just catching a lot of viruses, but I had never in my life had two viruses that were exactly the same, and now I'd had a half dozen in a year. I could predict what symptoms would occur day by day. The only thing that made sense was that my immune system wasn't working correctly.

When I finally got my diagnosis of ME/CFS, a full year after getting sick, I was hungry for information and devoured everything I could find about ME/CFS--in books, on websites, and through the other people I was gradually finding online. I discovered that my instincts had been correct and that a dysfunctional immune system is at the heart of ME/CFS. Although the exact cause of ME/CFS is still not known, its immune system abnormalities have been documented in dozens of research studies. Most experts agree that in most cases, there is some sort of infectious agent that triggers immune system dysfunction and that the dysfunctional immune system is the engine that sustains the illness and causes a cascade of domino effects in the endocrine and nervous systems that lead to our substantial and disabling symptoms.

Why Immune Dysfunction in ME/CFS is Unique
Most illnesses of the immune system fall into one of two categories.  There are deficient immune system, like AIDS, where the immune system is suppressed and doesn't respond properly to infectious agents. On the other side, there are auto-immune diseases, like MS, lupus, rheumatoid arthritis, and others, where the immune system is over-active and not only over-reacts to infections but also attacks the body itself. Unfortunately, ME/CFS does not fit neatly into either of these categories. This means that established treatments for the two main types of immune problems, such as treating auto-immune disease with steroids, don't usually work for people with ME/CFS.

One of the most fascinating things that I learned in that second year of illness was that ME/CFS has characteristics of both types of immune system disorder: parts of our immune system are over-active and parts of it are under-active. This is sometimes referred to as a Th1-Th2 imbalance or a Th2 dominance. Now, AP Biology was many years ago for me, so I'm no expert, but here is my understanding from what I have read. The Th1 and Th2 referenced above refer to two different types of T-helper cells, part of the immune system. Th2 cells generally respond to viruses and allergens, among other things, while Th1 cells respond to bacterial infections (among other things).
Note that there is not complete agreement among scientists and experts on the role of Th1 and Th2; some sources say that Th1 are responsive to viruses and Th2 to bacteria. I have stuck with this explanation here because our own personal experience fits this theory perfectly; however, it might be different for you.
ME/CFS is thought to be characterized by an imbalance, where our Th2 cells dominate. This means, in simple terms, that when someone with ME/CFS is exposed to viruses or allergens, our immune systems over-react, creating the kind of cold or flu-like immune response I described above, all signs that the immune system is responding (even in a healthy person, most viral symptoms are caused by the immune system response, not by the virus itself). This is why just being exposed to someone else's cold can cause a severe crash, even though we don't actually "catch" the cold and why many of us have problems with allergies and food intolerances that we didn't have before ME/CFS.

On the other hand, with fewer Th1 cells around, our immune systems under-react when exposed to bacterial infections. This is why people with ME/CFS are extra-susceptible to sinus infections,  bronchitis, and other secondary bacterial infections. For instance, my son and I rarely catch colds, but if one of us got even a bit congested, we would quickly develop bacterial bronchitis, requiring treatment with antibiotics. (I am using past tense because treatments to normalize our immune systems have greatly improved this problem; we used to each get bronchitis 4-5 times a year, and now we each get it only every 18 months-2 years!)

This also explains why those of us with ME/CFS often have bad reactions to vaccines, causing lengthy relapses or even acting as the trigger that starts ME/CFS. It's not the fault of the vaccine: it is doing what it is designed to do, stimulating the immune system to create antibodies. But, with our overactive Th2 cells, we respond with a prolonged immune response (i.e. crash) that would not happen in a healthy person. I have long believed that allergy shots were the trigger for my own ME/CFS for this reason. I have also observed over the years, for both of my sons and me, that our worst, longest-lasting crashes are usually those triggered by exposure to a virus, like when kids at school have colds or my husband gets the flu.

This is a VERY simplified explanation of a very complex process that is happening in our immune systems. There have been lots and lots of research studies detailing dozens of different types of dysfunction in the immune systems of those with ME/CFS, and each of these problems causes other problems, in a cascade of cause-and-effect. People with ME/CFS generally have low Natural Killer Cell function and all sorts of problems with our cytokines (where levels of certain cytokines are high and others low). As an example, this study from Stanford looked at the cytokine "signature" in ME/CFS patients, as a way to predict disease severity, and this comprehensive study from Columbia Medical School (which involved a who's who of the nation's top ME/CFS experts) took a look at all sorts of immune system markers in ME/CFS and were able to differentiate between the early stages of illness and later stages.

To Share with Your Doctor
One of the best resources I have seen in all these years is an older but still excellent article written by Dr. Nancy Klimas, published in 2007 in Current Rheumatology Reports, that details all of the known (at the time) abnormalities in ME/CFS patients' immune systems and how these lead to dysfunction in the endocrine and nervous systems. The paper is brief but contains dozens and dozens of references to scientific research studies that document these abnormalities, making it perfect to share with your doctor. I especially like to give this article to doctors who don't understand ME/CFS or don't believe it is real because it provides lots and lots of hard scientific facts on the physiological basis of ME/CFS.  Even though it is older and the science has advanced much further since it was written, it is still a good summary, all in one place. I think this one article alone can change the minds of skeptical medical professionals!  You can look at an abstract of the article online or read or download a pdf file of the entire article (it's 6 pages long).

So that is a very general overview of immune system abnormalities in ME/CFS (please remember that I am not an expert in this field--if you see I have made a mistake in this post or know of other information that might be helpful to others, please share it in the Comments section or send me an e-mail).


So What Can You Do About It?
Since immune system dysfunction is at the heart of ME/CFS, treating it can help to improve all symptoms. Although people with ME/CFS should avoid treatment that either suppress the immune system (like steroids) or "boost" it, there are a few medications and supplements available that can help to modulate or normalize the immune system. This blog post on Treating Immune Dysfunction in ME/CFS includes information both on improving immune function (which should help to improve ALL symptoms) and on treating underlying infections.

The three main treatments that have helped my son and I the most over the years in normalizing our immune systems are inosine, low-dose naltrexone, and glutathione - there are links to more information on all three in that post linked above. All three of those treatments are very inexpensive and easily accessible (inosine is even sold as a supplement) and have tremendously improved our conditions.
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32 comments:

  1. This is excellent, Sue and helpful even to me, who has been sick for so long. You are such a storehouse of info. Thank you!

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  2. Thanks, Renee. BTW, the Th2 dominance also explains why those of us with CFS have such difficulty getting rid of Lyme and other bacterial co-infections - our immune systems don't fully respond to them.

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  3. What a great write up Sue! It was so helpful for me to read. I should know but I never understood the immune dysfunction involved.

    I feel like printing out your post and taking it to my next MD appt.

    Thank you!

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  4. Sue
    thanks for a very imformative post.
    the TH reaction makes sense to me. i have been spending 8 years reducing the effects of mercury poisoning(dental amalgams).i never get sick but get bacterial side effects all the time. I am presently doing a 28 day course of infused ABX to try to get rid of a leaking elbow bursa sac.

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  5. Anonymous7:35 AM

    thanks for the info in the blog which i think is similar to the views of Dr. Myhill in the UK and thanks again for your emails Peter

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  6. Thanks, everyone, for the kind words of support! I'm glad you're finding this helpful.

    I should emphasize that the Th1-Th2 imbalance is only a part of the many immune system abnormalities we experience with ME/CFS...but learning about it did help me understand our illness better.

    Sue

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  7. I'm curious to see what other immune problems research uncovers over the next while, especially with the success of the team in Norway. M.E. has always been a very "immune" experience for me and I too, believe that at least in my case it's at the heart of the disease.

    I've tried 3 anti-virals so I'm curious to hear what Imunovir is doing for you to help? I'm cautious to try another one do to some pretty sig. reactions I had with my recent 5 mo course of Valtrex.

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  8. Upnorth -

    Immunovir is an immune system modulator, not an anti-viral, so it is entirely different from Valtrex and other anti-virals. Your significant reaction to Valtrex was most likely a herx reaction - a positive sign that the med was killing off viruses in your body.

    I will try to get to the Immunovir post tomorrow...but it's a really busy week here, and tomorrow is Craig's birthday! We'll see how the day goes...

    Sue

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  9. Thanks for the excellent post Sue. My brother felt awful for several days after getting a flu shot recently, and I told him that is a common occurrence for those with CFS. However, I couldn't explain WHY that happens, so passing along your post to him for more info.

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  10. David -
    Yes, that kind of reaction in a healthy person is fairly common, too. It's the same mechanism - the immune system is stimulated by the vaccine to create antibodies, which sometimes results in some mild flu-like symptoms (not from the vaccine itself but from your body's response to it). Of course, it;s typically mild and short-lived in a healthy person. I got a flu shot last year that triggered a month-long crash!

    Sue

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  11. Sue, this particular reaction I had was felt by both me and my physician to be clearly a "side effect" of the meds that occurs in about 7% of long-term users. That being said, I was probably having some herxing going on as well. Either way, I'm not going on Valtrex again...that was my third shot.

    However, perhaps we would try an immune modulator like Imunovir, I'll see what my specialist has to say about it next time I see her.

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  12. Upnorth -

    Oh that's a shame! I know some people have had good luck with anti-virals. I've been on Valtrex or Famvir for several years - it has helped a little but not a lot. My EBV and HHV-6 numbers are positive but not all that high.

    Sue

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  13. This is really nice information for ME/CFS patients.

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  14. Elaine5:22 PM

    Really useful info Thank You

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  15. Your brain is working much better than mine for you to have an understanding of TH1/TH2. Although dx with fibromyalgia, I also have high antibody titers to EBV, HHV-6, and CMV. I tried Famvir about a year ago and it gave me terrible nausea. I took it for 6 weeks, took a week off, and tried again for another 2 weeks and then quit. Knew it was probably a Herx reaction but just couldn't take it any longer. Will be talking to my neurologist about getting rid of the viruses and getting her input.

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  16. Anonymous10:57 AM

    You rock girlfriend!

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  17. Colin Smith2:02 PM

    Hi, I recently had surgery to remove a tumour in the bladder followed by a course of BCG auto immune therapy. The BCG brought on attacks of ME/CFS from which I have suffered for many years.

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    1. Interesting, though not surprising! I'm not familiar with that particular treatment, but anything that messes with the immune system will cause problems with ME/CFS. I know one guy who developed ME/CFS for the first time after chemo - it can act as a trigger, too.

      Consider trying some of the immune modulators that are helpful in ME/CFS - they might help you pull out of this relapse and won't hurt your tumor treatment since they don't suppress or stimulate the immune system but help to normalize it. Here's more info:

      http://livewithcfs.blogspot.com/2014/09/treating-immune-dysfunction-in-mecfs.html

      And one other treatment that has helped our immune systems normalize more recently:

      http://livewithcfs.blogspot.com/2017/03/increasing-glutathione-in-mecfs-related.html

      Good luck! Thanks for taking the time to comment and share your experiences.

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  18. This is very interesting. I have also read that there is a link to a condition called mitochondrial dysfunction, this is where the muscle is unable to uptake energy from the body properly.

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    1. Yes, mitochondrial dysfunction is a part of this disease, too, though the immune dysfunction is at the heart of the disease and the most likely culprit (often triggered by some sort of infection) that sets off the chain reaction of dysfunctions. It's a complex disease, but it can be effectively treated, one piece at a time.

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  19. I tried to look at the Nancy Klimas paper today but both the abstract and full report links are broken. I couldn't find it elsewhere (but my search was imperfect as I don't know the title). Please could you re-add the links?

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    1. Hi, Jenni -

      Thanks SO much for letting me know some links weren't working! They tend to change over time, and it's hard to keep track with 13+ years of blog posts, so I appreciate the heads up.

      I not only fixed the links, but updated the entire post and added some additional links to more recent studies on immune dysfunction in ME/CFS.

      Hope that helps!

      Sue

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    2. Very interesting. Thanks for this. I have been wondering about the immune system response and this explains the conflict between immune system suppression and going into overdrive. I always knew from young adulthood or earlier that to get a cold as other people describe it was something of a misnomer for me. It was never 'just a cold' but was more like how others would describe flu. Then in my mid thirties I suffered pleurisy twice in the same year (although I never knew whether it was bacterial or viral because I think they prescribed antibiotics from the off as a precaution.) This seemed to trigger Fibromyalgia pain although I wasn't diagnosed with this until I was 50. However over the years since then the main problem has been the fatigue and I was only diagnosed with ME/CFS last year, even though I've had the symptoms for years. Like you, I have had other chest infections from time to time which have dragged on and after a week they prescribe me with antibiotics and every time I start to feel better within 24-48 hours of taking them (so this is suggesting to me that there is some bacterial/secondary infection). I am now wondering how this implicates us for coronavirus (I did read your blog on this - this is how I found it from a Facebook link!) I know people with AI illnesses such as Lupus and all with MS report getting fewer colds too, although this could also be because - like me - they a) don't go out very much and b) because they are also very vigilant and take active steps to avoid them, just as is now being advised to avoid coronavirus. Oh and recently I have had a positive ANA test although none of the other tests they take in conjunction with this suggested an AI disease necessarily (although didn't rule one out either!)
      I've not had the flu jab, not for any other reason as I didn't get round to it because even though I am over 60 and have an underlying illness (ME, FM and a history of chest infections) I wasn't considered to be in one of the NICE guidelines 'at risk' groups. I could have paid for one privately at the pharmacist but as I say I just didn't get round to it.
      On a completely different subject, one of my most distressing symptoms which I've recently learned is part of Autonomic NS Dysfunction is Hyperhidrosis (excessive sweating) which for me is triggered more in the cold weather and is exacerbated (now) by anxiety

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    3. Thanks for your comment, Kate. Your positive ANA is very common for those with ME/CFS - most of us have that or at least a borderline result. We don't get the flu vaccine for all the reasons described in this post. We did one year (with the H1N1 scare), and I crashed for a month from it. Since I haven't caught the flu in the 18 years since getting ME/CFS, and my son has only had it once in his 16 years with it, I figure we are pretty safe! Hoping it is the same for coronavirus. Things are heating up quickly here in the US.

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    4. Many thanks Sue. That's very interesting what you say about a positive ANA which is proof enough that something is going on with ME/CFS (so many people don't believe it exists as they say there are no blood tests or definitive markers). Are you in the US? I'm sure I read where you were from on your blog but foggy brain has forgot. I can check after I have posted this! I'm in the UK anyway. Best wishes :)

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    5. Yes, I am in the US (state of Delaware). Yes, that will be a big breakthrough, when we finally have biomarkers doctors can test for!!

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    6. Thanks Sue. It's strange but in some international groups I have posted that I have M.E. and some people from the US have said 'what is ME?' I understand that it's also known as something else there but can't for the life of me remember the initials!

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    7. Ugh, Kate...unfortunately, our government saddled us with Chronic Fatigue Syndrome (CFS - which is why I use ME/CFS here) - everyone hates the name but that's what most doctors and patients recognize. ME or at least ME/CFS is beginning to catch on among patient groups, but it's still mostly CFS in the mainstream.

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    8. Yes ME/CFS used here in the UK too by the services. And yes, they say CFS was coined to downgrade ME but the two seem to be used interchangeably now.

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    9. I know some do say that...but it's not what actually happened. Our CDC just came up with its own name to what they decided was a new "mystery" illness when an outbreak occurred in the 80's in Nevada. They didn't realize the UK had already defined the same illness as ME - just wasn't on the radar here. Unfortunately, CFS has caught on worldwide now - wish it had been the other way around!

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