Friday, April 24, 2015

Ground-Breaking Research Into ME/CFS Immune Dysfunction

I am about two months late with this exciting update in the world of ME/CFS research. I've had more than my share of bad days this winter and spring, and I also wanted to gather more information so that I could better explain the impact of this ME/CFS research breakthrough.

On February 25, Columbia University's Mailman School of Public Health (note: major university) announced the results of its Center for Infection and Immunity's exciting new research to identify the exact characteristics of the immune dysfunction in ME/CFS. Columbia sent out a press release summarizing the research, with the full study report available here.

A word of warning before you read the press release or any news stories based on it: whoever wrote it was very poorly informed about past ME/CFS research and proclaimed this new study, "the first robust physical evidence that ME/CFS is a biological illness as opposed to a psychological disorder." Eeek - yeah, completely cringe-worthy.  Someone in PR got a bit carried away with that one. Of course, we all know there have been plenty of studies showing the physiological abnormalities present in ME/CFS over the past two decades. Back in 2007, Dr. Nancy Klimas summarized many of these findings in her report, Chronic Fatigue Syndrome: Inflammation, Immune Function, and Neuroendocrine Interactions, which cites over 30 different scientific studies (and by the way, is an excellent scientific article to share with doctors). Since then, there have been more studies on immune dysfunction in ME/CFS.

So, try to ignore the flagrant errors in the headlines surrounding this new study, and let's instead focus on what IS ground-breaking about it:
  • It was the largest ever (by far) study of ME/CFS immune dysfunction, involving almost 300 patients and over 350 healthy controls from multiple locations. Since many previous ME/CFS studies have been very small (often due to a lack of funding), the mere size of this study is big news. The smaller studies are often ignored in literature reviews, like those recently done/in progress with P2P and IOM - this one will not be ignored.
  • It was also the broadest ever immune study of ME/CFS in terms of scope, looking at 51 different immune biomarkers in blood plasma samples.
  • It was headed up by a world-renowned virologist, Dr. Ian Lipkin, which brings immediate credibility and visibility to the study (something ME/CFS studies rarely get) and included eleven other co-authors who include the world's top ME/CFS clinicians and researchers, including Dr. Nancy Klimas, Dr. Daniel Peterson Dr. Jose Montoya, Dr. Susan Levine, Dr. Lucinda Bateman, and more. This combination of credible outside researcher plus top ME/CFS specialists is unique to date.
  • For the first time ever, this study identified significant differences in immune function between early ME/CFS patients (less than three years) and those who've been ill for more than three years.
In short, the study showed that early-stage patients who'd been sick for less than three years showed elevated levels of many different cytokines (immune markers), indicating an immune system over-reaction that is familiar to all of us who've suffered from recurring sore throats, swollen glands, flu-like aches, and other immune-related symptoms. These results support the long-held theory that ME/CFS is a "hit-and-run" event, where some sort of infectious trigger (mono and Lyme are common ones) sets off an immune system over-reaction that continues even after the infectious agent itself quiets down, similar to a car stuck in high gear. This theory has been generally accepted among experts and patients for many years, but this study provides even more evidence.

A completely new development from this study was the finding that there is a difference between early-stage patients and later-stage patients. Three years seems to be the turning point, and after that, certain immune markers (various cytokines) show a marked decrease. The report itself includes details of all 51 biomarkers measured - which ones were high in the early stages, which ones were low, and which ones shifted after the 3-year mark (there are lots of graphs in the report to help explain the results).

One thing that confused me - and that I'm still not certain I completely understand - is how this new research fits into the already-understood aspects of immune dysfunction in ME/CFS. Two points have been reiterated over the many years of studies:
  • ME/CFS is neither a condition of autoimmunity nor of immune deficiency; instead, our unique type of immune dysfunction is a mixed bag - certain immune elements are over-active and others are under-active.
  • ME/CFS is a condition of Th1-Th2 imbalance, usually identified as Th2 dominant. I explained this in an earlier post about immune dysfunction in ME/CFS, but briefly, it means that our immune systems tend to over-react to viruses and allergens and under-react to bacterial infections, among other things. Certainly, our own experiences here, with my sons and I, have always born this out - allergies got worse with ME/CFS, we developed new food intolerances, we rarely "catch" viruses like colds or flu (though the resulting immune stimulation from exposure can feel like a virus), and any tiny bit of congestion always turns into a secondary bacterial infection, like bronchitis or a sinus infection.
From what I read about this new study, it doesn't negate those previously held theories about ME/CFS but adds more detail to our understanding of the immune dysfunction and shows new evidence of a difference between early and later-stage disease that hadn't been observed in a research setting before.  Personally, my son and I still seem to have the same type of immune dysfunction (though definitely fewer sore throats), though that may be in part due to our treatments aimed at normalizing the immune system which might reduce these differences. If anyone knows differently or understands it better than I do, please share your knowledge!

Finally, I asked a few questions of Dr. Susan Levine who is a co-author of this study, Chairperson of the CFS Advisory Committee, and our own ME/CFS doctor. Her comments on the meaning and effects of this new study include:
  • The differences in early- and late-stage patients found in the study mirror what she often (though not always) sees in her own patients - newer ME/CFS patients tend to have more prominent immune-related symptoms like sore throat, swollen glands, flu-like aches, etc. while patients in the later stages of the disease tend to have pain and cognitive dysfunction as more prominent symptoms (of course, all have the tell-tale exhaustion and post-exertional crashes).
  • As for immediate applications for patients, that is probably still a bit farther off. She said that the kind of cytokine testing done in the Columbia study is not yet available in commercial labs. This may not change anytime soon until there are ways to treat the abnormal cytokine levels - currently, there is no impetus for labs to add these tests.
  • In comparing the short-term and longer-term patients, she said they "are also looking at site variability, differences in gender and ethnicity and other environmental influences (urban vs suburban vs country dwellers) to see if there is an impact."
  • "While these are interesting findings, it would be good to look at T, B, and NK cells in addition, as well as autonomic dysfunction, metabolic changes, and pain levels in these `short duration' versus `long duration' patients to see if there is some additional correlation with other parameters."
So, essentially, this is exciting new research that does represent some breakthroughs and new ideas, though there may not be much immediate effect that patients will see. The finding of a difference in short-and long-term patients will certainly be of interest to clinicians who may slightly vary their treatment protocols for newer versus longer duration patients; however, the overall immune dysfunction is still a mixed bag, meaning that medications to suppress or stimulate the immune system will still have limited efficacy for ME/CFS patients. We are still best off trying to treat with immune modulators to normalize the immune system.

And, of course, this new study brought much-needed visibility to our disease and should provide plenty of fodder for further study and new interest from other outside researchers. And, hopefully, those silly headlines along with the hard data will finally put to rest the outdated idea that ME/CFS isn't a "real" disease.

Does this study fit with your own ME/CFS illness history? Did you notice a change or difference after the 3-year mark?

(For more information, see articles published by The Atlantic and by Science Advances.)


Unknown said...

Hi Sue- I have been ill for a long time with ME/Fibro-20+ years. Still suffer with sore throats, swollen glands and flu-like symptoms. Was lucky enough to get into the Neuro Immune Clinic NOVA and have bloodwork that showed my cytokines all over the place (along with active Epstein Barr and Rosella.) So I believe that I do not fit the 3-year mark study.

Unknown said...

Thank you for posting this Sue. I was bed-bound for the first two years then the next two were a mix of that and trying to function. It's been 9 years since I was diagnosed and I would say that my glands are definitely swollen most days, the sick feeling rarely leaves and the joint pain visits most weeks. My muscles scream most days but I think my cognitive function is getting better on the whole. So I don't think I fit into the 'early' or 'late' predispositions mentioned. Sue, many times, I don't have the concentration to read though your articles but REALLY want to. Are you able to add an image to your posts so that I can pin your post to Pinterest for later? Thank you for taking the time to put this post together, I imagine it was difficult for you. I hope you are well. Emma :)

At Home on the Rock... said...

I've had CFS for almost 8 years. For the first while (and I can't remember exactly as I had so much brain fog during that time, it's all a blur) I had really bad "cold" that I could not shake off. It lasted for months....lots of coughing (it seemed to have settled in my chest) where I could not get stopped. Also had a sore throat etc. After that time (at least two years but again am not sure exactly), it swung the other way and I've be exactly the opposite. I've never had a cold or a sore throat or the flu in several years (at least 4 or 5 years). My naturopath said my immune system (as she's seen through her tests) is "exceptional" and my kids often comment how I never get sick with the flu/cold etc.

I am more sensitive to other things though (food and medications sensitivities). I'm also more sensitive to other things too (eg noise bothers me more)

Sue Jackson said...

Dr. Levine said that not everyone seems to fit that 3-year profile. Based on my own experiences and what I've heard of others, I suspect that in most cases where someone doesn't improve over time and still has severe immune symptoms, there are often untreated infections present. You might consider looking into this.

As for Pinterest, I know nothing about it! I know I should learn about it, but I can barely juggle blogs, Twitter, Facebook, e-mail, etc. as it is :)

So, all I have to do is add an image to my post and that makes it "pinnable"? That's good to know - thank you! I will try to do that from now on.


Sue Jackson said...

Sounds like a pretty classic presentation and similar to our experiences here, too.

Colette said...

Hi. I have been ill since about 2009 and I had a c section 19 months ago and have been way worse since no idea why but it was a simple birth no complications I had a tiny infection in my wound site but healed it up fast. I seem worse now so not sure why but I maybe would of fitted the 3 year mark who knows

Sue Jackson said...

Hi, Colette -

The hormonal changes of pregnancy definitely have an effect on ME/CFS! Some people get better during pregnancy, some get worse, some stay the same. It was probably not the c-section but the end of pregnancy and shift in hormones that caused your worsening.

My CFS symptoms get much worse when I get my period because of the hormonal shifts so I take a 90-day birth control pill to keep hormone levels steady - helps me a lot!