Medical Matters > Aetiology: Immune System

ME Essential Summer 2020

Question

I keep seeing references to ‘low level immune system activation’ being an important research finding in ME/CFS. But what does this mean in language that I can understand?

Answer

In very simple terms, the immune system is a bit like an army in that it has many different components – all with different jobs to do when it has to deal with an invader in the form of an allergy or an infection. We know from numerous research studies into ME/CFS that if you look very carefully at the immune system you can find abnormalities in many of these different components – antibodies, autoantibodies, T-cells and cytokines to name but a few.

But none of them are sufficiently consistent or significant to link in with symptoms – with the possible exception of cytokine dysfunction. Cytokines are one of the front line troops of immune system, and are chemicals that are produced during the very early stage of an infection. They also help to produce the characteristic symptoms of any infective illness – fatigue, muscle and joint pains, loss of appetite, increased sleep requirements etc. One of the more consistent abnormalities in recent research into immune system dysfunction in ME/CFS involves increases in specific types of cytokine. And this makes some sense in relation to a link to symptoms because ME/CFS involves feeling as though you have a constant dose of Flu.

Because this type of cytokine abnormality equates to immune system activation we tend to refer to this finding in ME/CFS as being low-level immune system activation. Further support for immune system activation comes in the form of an interesting brain-scan research study from Japan. This research found evidence of what is called neuroinflammation, which could be linked to increased levels of these inflammatory chemicals entering the brain and central nervous system. We use the term low-level because this is a fairly subtle abnormality concerning cytokine production and not the massive release of cytokines that may accompany an acute infection.

Centres for Disease Control (CDC)

“It is possible that ME/CFS is caused by a change in the person’s immune system and the way it responds to infection or stress. ME/CFS shares some features of autoimmune illnesses (diseases in which the immune system attacks healthy tissues in own body, like in rheumatoid arthritis). For example, both ME/CFS and most autoimmune diseases are more common in women and both are characterized by increased inflammation. However, other signs of autoimmune disease, like tissue damage, are not found in patients with ME/CFS.

“Scientists think that the immune system might be contributing to ME/CFS in other ways, including:

  • Chronic production of cytokines (cytokines are proteins that are produced by the immune system and regulate behavior of other cells). Higher levels of cytokines for a prolonged period can lead to changes in the body’s ability to respond to stress and might lead to the development of health conditions, including ME/CFS.
  • Low-functioning natural killer (NK) cells. NK cells are cells of the immune system that help the body fight infections. Many patients with ME/CFS have NK cells with lower functional ability to fight infections. Studies have found that the poorer the function of NK cells in ME/CFS patients, the worse the severity of the illness. NK cell function tests are hard to do and their results are not reliable outside of research studies. Because of this problem, NK cell function testing is not yet useful for healthcare providers. Also, low NK cell function can occur in other illnesses and thus cannot be used to diagnose ME/CFS.
  • Differences in markers of T-cell activation. T-cells are cells of the immune system that help activate and suppress immune responses to infections. If they become too active or not active enough, the immune response does not work as it should. However, not all patients with ME/CFS appear to have these differences in markers of T-cell activation.”

CDC: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Possible Causes | July 2018

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MEDICAL DISCLAIMER

Medical Matters is for information purposes only. The answers provided by Dr Shepherd and the ME Association’s other expert advisers should not be construed as medical advice. We recommend that any information you deem relevant is discussed with your GP as soon as possible. It is important to obtain advice from a GP who is in charge of your clinical care, who knows you well, and who can consider other likely causes for symptoms. Seek personalised medical advice whenever a new symptom arises, or an existing symptom worsens. Don't assume that new or worsened symptoms are a result of having ME/CFS.

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