by Sasha Nimmo
A paper published in Metabolic Brain Disease by Morris, Maes, Burk and Puri suggests Myalgic Encephalomyelitis develops because of genes responsible for immune responses. Their paper discusses how molecules may convert an acute infection into a state of escalating chronic systemic inflammation.
Morris and Maes have written extensively about chronic fatigue syndrome and Myalgic Encephalomyelitis. Morris is an independent researcher and Maes is affiliated with Thailand’s Chungalongkorn University (previously associated with Australia’s Deakin University). In 2015 Maes proposed a new name, case definition and biomarkers: Neuro-Inflammatory and Oxidative Fatigue.
In ‘Myalgic encephalomyelitis or chronic fatigue syndrome: how could the illness develop?‘, the authors lay out an explanatory model of illness development and progression, commencing with a proposed mechanism explaining the development of chronic systemic inflammation, oxidative and nitrosative stress (I&ONS) following a pathogen invasion in genetically predisposed individuals.
The authors say variation in immune response genes plays a major role in determining the development of ‘damage associated molecular patterns’ after an infection, as these molecules can ‘convert’ an acute pathogenic infection into a state of escalating chronic systemic inflammation. They say this concept leads to a novel explanatory model which explains the major biological observations.
“There is also evidence of a longitudinal shift in the immune profiles of patients, with an inflammatory phenotype seen in early disease giving way to an anti-inflammatory or immunosuppressed phenotype, indicating activation of the compensatory anti-inflammatory reflex system.”
Numerous research teams reported activated but dysregulated immune systems with elevated pro-inflammatory cytokines, T cell anergy, natural killer cell dysfunction, and Th1, Th2 and, possibly, Th17 lymphocyte biases being repeatedly reported, citing Hornig, Montoya, Peterson, Brenu (Australia’s Griffith University) as well as Maes’ own work.
The authors’ point out the wide range of definitions of chronic fatigue syndrome (more than 20 in current use) lead to inaccuracies and there are only a few criteria where there is evidence of immune abnormalities. This is causing problems in medical research.
“This is an important issue as the use of narrow selection criteria identify patients with far higher levels of physical and cognitive disability than the use of wider criteria and criteria variance has been identified as the main factor accounting for the lack of replicated data which has impeded progress in this field.”
While cohorts are important, so is medical research funding. In the USA, if the burden of disease was taken into account, then funding should increase 25-fold, citing Dimmock’s work. Australia has a poor record of funding research, the last study it funded was in 2005.
While some infections are associated with chronic fatigue syndrome, the paper’s authors’ note that there is no consistent results so ‘it is difficult to conclude that persistent or chronic infections are at the root of CFS/ME/SEID, but of course they could be in some patients’.
The paper explains that chronic engagement of toll-like receptors (TLRs) by ‘damage associated molecular patterns’ (DAMPs) leads to the development of a positive feedback loop, whereby increasing tissue damage perpetuates and escalates pro-inflammatory responses, leading to a state of chronic inflammation, ONS, mitochondrial dysfunction and glial cell activation.
The authors point out these also affect other diseases: chronic engagement of TLRs and other receptors is implicated in lupus, rheumatoid arthritis and MS, while the presence of DAMPs can lead to chronic activation of the inflammasome which is implicated in the development of neuro-inflammation and abnormal central nervous system signalling characteristic of neurodegenerative and neurodevelopmental disorders.
Here is the full paper.