Following her introduction last week, Dr Eleanor Roberts now takes a look at some of the ways in which the immune system may be disrupted in ME/CFS. Have a look back at her previous article for a reminder of some of the cells and processes discussed here.
While there is evidence that the immune system is disrupted in ME/CFS, unfortunately it is hard to pin down what that disruption is, or to identify a single, universal problem. Furthermore, individuals may have more than one cause of their own particular symptoms.
Proposed causes of ME/CFS that involve the immune system include the following:
- Continued activation of the immune system’s response to foreign molecules (antigens) – known as the cell-mediated immune response.
- Long-term changes to the type and function of T-cells in the body.
- Bacteria from the digestive system passing from the gut to the rest of the body – known as bacterial translocation or ‘leaky gut’ – which can lead to a type of autoimmune reaction.
- Increased levels of lysozyme – an enzyme targeted at invading pathogens – which reflects activation of immune and inflammatory pathways.
As immune activation takes a lot of energy and can lead to chronic inflammation, this is one proposed link with the extreme fatigue experienced by those with ME/CFS. Scientists looking at the cause of ME/CFS have largely focused on individual parts of the immune system, and some of these findings are summarised here.
T-cells
Some subtypes of activated T-cells may be disrupted in people with ME/CFS – while some markers of this activation are increased, others are decreased. For instance, some studies found a change in the balance of different types of T-helper cells, which can alter the cytokines released and hence the inflammatory response. Another study found a disruption in a specific type of T-helper cell involved in the immune response, autoimmunity and chronic inflammation, suggesting that these cells were in an ‘exhausted’, chronically activated state. This was proposed to be due to a shift towards more harmful bacteria in the gut.
Natural killer cells
Many studies have found that natural killer cells and/or their usual cell-killing (cytotoxic) activity are reduced in people with ME/CFS, possibly reflecting a chronic or persistent viral infection. This reduction may be due to increases in anti-inflammatory regulatory T-cells (which have also been shown in ME/CFS), reflecting immunosuppression and a disruption to the balance of the immune response.
Inflammation
One theory about ME/CFS is that the immune-system response to a pathogen or other stimulus remains even after that pathogen/stimulus is gone or inactive. ME/CFS includes aspects of both an inflammatory reaction and (especially in the long term) an anti-inflammatory or suppressed immune reaction, but few studies agree on a persistent, reproducible pattern of response.
Cytokines
One way of studying inflammation is to look at the chemicals involved in this process: cytokines. The cytokine picture in ME/CFS is complex with some studies showing increased levels, some showing decreased levels, and some showing no differences. These inconsistent results are possibly due to differences in how the studies were carried out, and also in the patient subtypes studied.
One study – which examined cerebrospinal fluid – showed an increase in immune system-related cytokines involved in either pro-inflammatory or anti-inflammatory actions. This was proposed to be due to competing inflammatory and regulatory immune-system activity in people with ME/CFS. Other findings include differences in the levels of inflammatory cytokines in the blood according to ME/CFS severity. However, other studies have not shown any differences in cytokine levels when comparing people with ME/CFS to those without.
Next week, Eleanor looks at more immune-system research in ME/CFS, including the potential roles of ‘leaky gut’, B-cells and immunoglobulin.
