Immune Problems May Leave Chronic Fatigue Syndrome Adolescents Open To Infections

September 30, 2012

A study suggests adolescents who come down with chronic fatigue syndrome after an infection may have an immune abnormality that allows pathogens to be activated.

Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue. Broderick G, Katz BZ, Fernandes H, Fletcher MA, Klimas NG, Smith FA, O’Gorman MR, Vernon SD, Taylor R. J Transl Med. 2012 Sep 13;10(1):191. [Epub ahead of print]

Broderick, Fletcher, Klimas, Vernon, Taylor… this big  NIH funded study was loaded with top ME/CFS researchers.  Similar to the Dubbo studies in Australia, the study followed people, in this case, adolescents, who came down with an infection (infectious mononucleosis), to see who came down with chronic fatigue syndrome and why.  Citing the many published studies linking ME/CFS onset to pathogens the authors emphasized the strong link to infection found in this disorder.

There remains an overwhelming  body of evidence reinforcing the link to an infectious etiology in at least a subset of CFS patients

Thus far  Taylor has found  that six, twelve and 24 months later 13%, 7% and 4 % of the adolescents who came down with  infectious mononucleosis met the criteria for chronic fatigue syndrome 6, 12 and 24 months later. Encouragingly, these are strikingly similar percentages to those found in other studies tracking infectious events.  Given the wide range of documented pathogen triggers (EBV, Cytomegalovirus, HHV-6, Q-fever, Ross-River Virus, enterovirus, parvovirus B-19, giardia) it’s probably time to wonder if ANY serious infection is going to leave a subset of those afflicted with ME/CFS for a significant period of time. If that’s true then this disorder may be far more common than anyone has suggested yet.

In this study the researchers examined 16 immune factors called cytokines using the latest methods and gave their analysis a twist; since cytokines usually co-occur together they looked at ‘combinational effects’ to see if suites of cytokines showed up together.


First they found IL-8  was increased and IL-23 was decreased in people with post-infectious CFS.  Then using a more sophisticated analysis they found that they could predict 80% of the people who came down with ME/CFS simply by examining the levels of 5 cytokines (IL-2, IL-6, IL-8, IL-23 and IFN-y) in their blood.

Focus on IL-8

Il-8 has all sorts of interesting potential tie-ins with ME/CFS. We know the sympathetic nervous system (fight or flight response) is over-activated in this disorder and IL-8 has been linked to sympathetic nervous system induced pain, to  pain in fibromyalgia (FM), and is up-regulated in a key brain region (the anterior cingulate cortex (ACC)) believed to play a role in both chronic fatigue syndrome and FM.  IL-8 is also produced by cells with toll-like receptors that participate in the early, innate immune response which has been showing up in spades in CFS research recently.

The fact that these researchers were able to pick out 35 of the 42 ME/CFS patients simply by measuring five cytokines demonstrated the group was in the grips of a substantial immune dysregulation.

Pathogen Fighting System May Be Blunted in Adolescents with CFS

But what kind of immune dysregulation? Four of the five cytokines highlighted in the study play a role in the Th17 system, an important player in the fight against opportunistic infections and a known culprit in auto-immune diseases and inflammation.  This study suggested that a poorly functioning TH17 pathway could be preventing these young ME/CFS patients from clearing EBV from their systems. Interestingly, some studies suggest EBV may be able to modify the TH17 system, thus clearing the way for greater infectiveness.

Who Do These Findings Apply To?

The authors noted these findings could apply to patients with other types of infectious onset or they could be peculiar to this group. A recent study by this group in a more general population of ME/CFS patients found lower instead of the higher IL-8 levels found in this study.  The contrast between the two study findings outlines the high level of heterogeneity present in the ME/CFS community and the urgent  need to develop subsets


{ 7 comments… read them below or add one }

Mya Symons September 30, 2012 at 2:19 pm

This sounds like what happens to my son. Ever since he was really sick with an Adeno virus and in the hospital for over a month, he gets sick far longer than the average teenager. I think he was unlucky in that he inherited my and my husbands immune system problems. He has a lot of minor infections like ear and sinus infections and bronchitis. They found he also makes Anti nuclear antibodies only after he has been sick, which is strange. We got a letter recently from his school that he might want to consider home schooling. He is a smart kid and still getting good grades, so this is not going to happen. I the letter is because his teachers are inconvenienced.


Shell October 2, 2012 at 5:16 am

Hi Mya
Just thought I’d reasure you over home education. Teachers rarely suggest it as most of them are against it (although I have teacher friends who back my decision to the hilt)
Standards for home ed are excellent. If you live in the USA there are loads of accredited curriucla and even online schools (not sure of their standard though)
In the UK we can put our children through IGCSEs which are of a much higher quality than the school gcses and many HE youngsters go on to do A’levels or like my oldest daughter start University courses from age 15 onwards.
All the studies and research on homeschooling/home education shows it’s an excellent system and most children out perform their schooled peers.
My 7 yr old dd could never have gone to school – she isn’t well enough. Thankfully this wasn’t a major decision as I was already HEing her older siblings.
I do know how difficult the decision can be.
You may never need to do it, but please don’t think homeschooling would be less rigourous academically. It isn’t.


Mya Symons October 2, 2012 at 10:36 pm

Hi Shell. Thank you for the information. My niece was homed schooled through the internet and did not receive a good education. Unfortunately, I think things in the U.S. are different unless you have money to afford your own books and materials and are well enough to home school your children yourself. We are lucky though in that he is 17 and did not have problems until he was about 12 and is not sick all the time. So he only has one more school year to go and he is set on finishing. Thank you for taking the time to give me the information though. I am glad that it worked out for you and your daughter.

taniaaust1 September 30, 2012 at 11:17 pm

They really need to be taking a look at the long term outcome of teens who get mono too esp bad mono as they may find this group more likely to end up with ME/CFS sometime in the future (not necessarily right after the mono).

I had severe mono.. mostly bedridden for 10 weeks when a teen. I did fully recover except my memory was never the same (maybe the sky high temps I had damaged my brain?). 11 years later I got ME/CFS.

Im positive that I had such bad mono as a teen and then come down with ME/CFS 11 year later due to obviously something is wrong with my immune system (note I also didnt tend to get colds as a child .. seems I may of also been TH2 predominant). Anyway..something to do with my immune system I have always believed, predisposed me to these things.


Cort October 1, 2012 at 5:41 am

Very good point Tania! I wonder if they extended the study further if they would find people relapsing again….If the Dubbo Studies apply the people with the worst cases of mono would be the ones who relapse later. Certainly many studies suggest that early life stressors – which include infections – can put people at risk for disorders later in life; I think that’s pretty much agreed on…so why not strong infections that occur in adolescence as?

In fact, my understanding is that they’ve found increased rates of multiple sclerosis in people who came down with glandular fever/infectious mononucleosis in adolescence.


voner October 1, 2012 at 3:30 pm


you ever get a little tired of saying, “the urgent need to develop subsets.”? maybe nonstop repetition of that phrase to the keepers of the federal pursestrings might work.

thanks for your usual clear and Informative post.


Enid October 1, 2012 at 10:57 pm

I think this is brilliant Cort – in particular that some pathogen (we know the usual suspects) has not cleared the system causing immune dysregulation. Least that’s what I gather from these studies.


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