In the balance. Immune-system research in ME/CFS part 2

Here is the second part of Dr Eleanor Roberts’ article looking at ways in which the immune system may be disrupted in ME/CFS. Click here for part 1, and click here for Eleanor’s introduction to the immune system.

‘Leaky gut’

For some people with ME/CFS, their symptoms may be due to changes in the different species of bacteria found in the gut, and products from these leaking into the rest of the body. This can lead to a type of autoimmune-system reaction involving increased production of immunoglobulin (Ig) A and IgM from B-cells.

Gut permeability describes how tightly the cells that make up the lining of the stomach and intestines are bound together. Increased permeability (looser binding) may allow bacterial products into the bloodstream, leading to inflammation. Mast cells, which form part of the innate immune system and can be overactivated in people with ME/CFS, may be involved in this loosening of bonds between digestive-system cells.

Alterations in the types and activity of gut bacteria are associated with lower levels of the chemical butyrate, which has a number of roles including aiding the health of digestive-system cells and increasing levels of IgA. Another role for butyrate is in decreasing inflammation in the brain. A number of studies in ME/CFS have found increased activity of immune cells in the brain – called microglia and astrocytes – indicating brain inflammation, possibly related to the amount of butyrate present.


Several studies have found evidence of B-cell changes and disruption in ME/CFS. On the outside of each immune-system cell, including B-cells, are many receptors that help pass signals between them. Analysis of B-cell receptors in a person can give an idea of what the body as a whole has been primed to react to. A recent study found that people with ME/CFS had an increase in B-cells with one particular type of B-cell receptor, suggesting that this may be useful as a blood test to indicate ME/CFS.

Another receptor found on B-cells is the β2-adrenergic receptor, which is thought to have a role in immune function and the release of certain cytokines. These receptors are involved in regulating functions such as heart rate, breathing, emotional responses and memory. In some people with ME/CFS, researchers have identified increases in antibodies against these receptors, which may interfere with their actions and lead to increased inflammation.


Antibodies produced by B-cells are usually targeted at invading pathogens. However, if they are triggered by cells found inside the body, autoantibodies can be produced which are targeted against the body itself. This is known as autoimmunity. Some researchers believe that all of the immunological alterations seen in ME/CFS are associated with autoimmunity.

The ‘leaky gut’ described above may also lead to autoimmunity. If gut bacteria cross from the gut to the rest of the body, they may be seen as foreign by the immune system and trigger an autoimmune reaction. Some studies in ME/CFS have found increases in IgA and IgM from B-cells targeted on a type of digestive-system bacteria called Gram-negative enterobacteria, and this may lead to autoimmune-type inflammation.


While there is little doubt that disruptions in the immune system play a role in ME/CFS, no single, definitive system deficit has yet been identified. This suggests that the factors which initiate and maintain ME/CFS differ among individuals with the illness.

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