ME Awareness: What the research is telling us about the pathology of ME |11 May 2020

May 11, 2020

Dr Charles Shepherd, Hon. Medical Adviser, ME Association.

M.E. (myalgic encephalopathy or encephalomyelitis) is a complex multisystem disease with a wide range of disabling symptoms.

This free download summarises what we know about the pathology of M.E. and is based upon published research to date.


Understanding the pathology of M.E.

This leaflet provides a summary of what biomedical research is telling us about M.E. It considers key symptoms, common triggers, and explains how various aspects of disease pathology could be linked to specific symptoms.

All references for the research mentioned below, along with more detail, can be found in the ME Association’s Clinical and Research Guide and in the research reviews that are available free from our website.

Leaflet Extracts:

Predisposing and Triggering factors

There is no definitive evidence that can explain why people develop M.E. Factors that seem most likely include:

  • A genetic predisposition – which may explain why more than one family member can be affected
  • An infection – bacterial or viral
  • Trauma – physical or emotional
  • Exposure to toxins – including mould and pesticides
  • Vaccination

Key research explanations for symptoms and disease pathology

Blood and Plasma abnormalities

  • Blood flow and oxygen supply to cells may be reduced in ME/CFS.
    Red blood cell morphology – A recent study from America showed that red blood cells from ME/CFS patients are ‘stiffer’ and less able to change shape (called deformability) in order to squeeze through small capillaries. This suggests blood flow and oxygen supply to cells may be reduced in ME/CFS. This study was the subject of an MEA research review.
  • Plasma factor – Preliminary unpublished studies from several independent groups have now found that a factor in the blood plasma (a component of the blood that doesn’t include red blood cells) can affect cell metabolism in ME/CFS and that the effect can be transferred to healthy cells. They found that adding plasma from ME/CFS patients to healthy control cells made them increase their oxygen consumption, indicating the mitochondria were working harder. The factor in the blood responsible for these changes is yet to be identified.
  • ‘Nano-needle’ test – In 2019, Dr. Ron Davis from America presented results from a pilot-study testing electrical impedance (ability of a current to pass through cells) in ME/CFS and healthy cells in plasma. He found that putting the cells under ‘stress’ and making them work harder resulted in a dramatic change in signal. It’s as though the cells were unable to keep up with the added demand put on them. Interestingly, when plasma from ME/CFS patients was applied to healthy control cells, the same signal occurred. Suggesting a factor in the plasma was affecting the cells functioning.

Cardiac Function

  • Some studies have found results suggesting low cardiac output as an explanation for poor physical stamina and chronic fatigue (as a symptom).
  • There is also some evidence of hypotension (low blood pressure), especially on standing, which could explain symptoms such as fatigue, dizziness, cognitive issues, tremors, and nausea.


  • miRNA's represent potential biomarkers for diagnosis and drug treatment targets.
    Several gene polymorphisms (variations in DNA sequence) have been identified, which are involved in various processes such as immune modulation, oxidative stress, and energy metabolism.
  • Under and over-expression of certain genes and miRNAs (small molecules that regulate gene expression) may explain some symptoms and also account for an increased susceptibility to developing M.E. They also represent potential biomarkers for diagnosis and drug treatment targets. Recent findings from Prof Moreau et al. found that miRNAs might be used to place patients into subgroups.

Immunological Dysfunction

  • Activated immune system – studies have shown cytokine mediated, low-level immune system activation, in the blood and cerebrospinal fluid. This results in low-grade inflammation and a general ‘sickness response’, involving decreased appetite, wanting to sleep a lot and flu-like malaise and pain. Several studies have demonstrated altered levels of inflammatory markers, called cytokines, and activated immune cells, such as lymphocytes. ME Biobank researchers recently found highly increased levels of a type of immune cell called MAIT (Mucosal Associated Invariant T-cell) cells in severely affected patients. The study was the feature of an MEA research review.
  • Studies have shown cytokine mediated, low-level immune system activation, in the blood and cerebrospinal fluid.
    Poor cellular function – reduced Natural Killer (NK) cell activity is a common research finding. NK cells are a type of white blood cell that comprise part of the immune system and act like security guards, circulating round the body looking for potential threats. However, ME Biobank researchers recently reported no differences in NK cell number and function in patients compared to controls. The study was the feature of an MEA research review.
  • Autoimmune component – some studies have found activated T- and B-cells, as well as an increased incidence of autoantibodies (immune cells, that attack tissues of your own body, instead of targeting foreign cells, such as bacteria).

Continues with:

  • Metabolomics
  • Microbiome
  • Mitochondria, cellular bioenergetics, and exercise physiology
  • Neurology and neuroendocrinology


The most widely accepted model for M.E. is that it is a complex, multisystem disease which is triggered by an immune system stressor, commonly an infection, in a genetically predisposed individual.

Important clues are emerging, and new types of drug treatment are being assessed on the basis of these abnormalities.

The illness is then perpetuated by interaction of various changes in the brain, muscles, immune and endocrine (hormone) systems.

Until we have a better understanding of the underlying disease pathways, and the various clinical and pathological sub-groups, progress in developing a reliable diagnostic test and an effective form of drug treatment is likely to remain slow.

However, important clues are emerging, and new types of drug treatment are being assessed on the basis of these abnormalities. And there is movement on the central funding front with groups like the CFS/ME Research Collaborative (CMRC) working to advance the case for M.E. research investment.

Research provides the best chance we have of improving the lives of people affected by this awful disease. There is good reason to hope that M.E. research will be taken seriously in the UK and that effective forms of treatment will eventually emerge.

ME Awareness Week Monday 11th – Sunday 17th May 2020

Visit the ME Awareness Media Toolkit and download posters and graphics.

The ME Association

Ramsay Research Fund

We are a national charity working hard to improve the lives of people devastated by an often-misunderstood neurological disease. 

We believe biomedical research offers the best hope to people affected by M.E. If you would like to support our investment then please donate to the Ramsay Research Fund. 

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