When the body encounters a virus or other pathogen, the immune system can undergo long-lasting changes known as trained immunity. This process involves epigenetic reprogramming – altering gene expression without changing the DNA itself – to help innate immune cells respond more robustly to future threats.
In a recent review, Humer et al. propose that certain immune cells in ME/CFS may be abnormally hyperresponsive, contributing to ongoing immune system activation and disease mechanisms.
Although direct evidence in ME/CFS is still limited, according to the researchers studies in other post-infectious, infectious and autoimmune conditions offer insight. The review took a particular interest in COVID-19, whereby patients who had been hospitalised showed signs of trained immunity months after recovery, with immune cells like monocytes producing high levels of inflammatory molecules.
Reported in other diseases:
- Q fever, another post-infectious illness, shows prolonged immune activation and persistent fatigue symptoms.
- Sjögren’s disease, an autoimmune condition marked by fatigue and dryness, also shows features of trained immunity. Some ME/CFS patients share overlapping symptoms and lab markers with Sjögren’s disease.
Understanding these changes could help in better understanding ME/CFS.
Limitations
- Direct studies in ME/CFS are sparse – Most evidence comes from related conditions like COVID-19 and autoimmune diseases.
- Cause or effect? – It is unclear whether trained immunity and hyperresponsiveness cause ME/CFS symptoms or is a consequence of the disease. As mentioned before trained immunity is a normal response to infection.
- Patient variability – ME/CFS is a highly heterogeneous condition, and not all patients may exhibit the same immune patterns.
The researchers suggest future research should focus on identifying trained immunity markers – such as epigenetic changes and altered metabolism – in ME/CFS. This could help define subgroups of patients, develop new diagnostic tools, and discover more targeted treatments.
