Overview of interactions between the nervous system and immune system.

Science of ME/CFS

Overview of interactions between the nervous system and immune system.
The nervous system and the immune system can interact in the brain, at the nerve roots along the spinal cord, and at the nerve endings. Created for Phoenix Rising with BioRender.com

As of 2022, the science behind ME/CFS is still mostly unclear. For this reason, researchers are looking in many different directions to explain the biological cause and symptoms of ME/CFS.

But this doesn’t mean that research into ME/CFS is a recent phenomenon. In fact, researchers have studied outbreaks of ME/CFS dating back to the 1930s. If you would like to review a historical list of research papers, please see our Historical ME Research Literature.

If you are more interested in recent research papers, please see our list of great research summaries available from ME associations. You will find research into the neurological aspects of ME/CFS (including dysautonomia), into the immunological aspects (including autoimmunity), as well as research into cellular energetics and other areas.

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Examples of ME/CFS Science

Don’t know where to start? That’s okay. There’s a lot out there. One way to start exploring the science is to review the following example discussions from our community forum:

Epidemiology:

How many patients had their ME/cfs start with an infection? How many patients are still able to work? How many patients have a family member with ME/cfs? These are the sorts of questions that an epidemiological study tries to answer!

Neuroimaging:

Neuroimaging studies of ME/cfs patients have found significant findings. But how significant? A recent review took a top-level view of these studies.

Is it possible to “see” inflammation in the brain? How?

Exercise intolerance:

Patients with ME/cfs find that they are simply unable to exercise fully due to some physiological barrier. Researchers investigated patients during an exercise test and found evidence that suggests that the physiological barrier is actually dysautonomia of the small nerves that control constriction of large veins. Interestingly, this exact type of dysautonomia has also been proposed as the basis for orthostatic intolerance in ME/cfs!

Diagnostic criteria:

A brain MRI study compared “CFS” patients diagnosed with the outdated Fukuda diagnostic criteria to “ME” patients diagnosed with the newer International Consensus Criteria (ICC), along with a control group of healthy people. When comparing ME patients to healthy controls, significant abnormalities were seen in the brainstem. When comparing CFS patients to healthy controls, no significant abnormalities were seen!

Immune abnormalities:

Looking to make sense of the different studies on lymphocytes such as Natural Killer (NK) cells or Cytotoxic (CD8+) T cells? Here’s a summary of those studies!

Many studies have found low NK cell function or low CD8+ T cell function, but attempts to replicate these findings have been inconclusive.  Here is a study that combined findings from NK cells and CD8 T cells in a way that may provide a stronger diagnostic test for ME/cfs.

A research study found that some people with ME/cfs show a deficiency in the subclass of antibody known as IgG3 or a deficiency in the immune molecule called Mannose-Binding Lectin (MBL), confirming a 2015 study and prior reports. Could this be a subtle form of immune deficiency?

Auto-immunity:

Many ME/cfs patients show signs of auto-immunity. But where does this auto-immunity come from? Although the causes of auto-immunity are still poorly understood, research suggests that chronic inflammation, or chronic infections, are the likely causes of auto-immunity.

Endothelial dysfunction:

What exactly is “Endothelial Dysfunction”? And what does the scientific research say about its relation to impaired blood circulation in ME/cfs?

Cellular fuel sources:

A scientific paper finds that ME/cfs blood cells may have an increased energy demand that is not satisfied by burning glucose for energy. Instead, it hints that glutamine, fat, & branched-chain amino acids (BCAA) are burned for energy!

A science article may provide more evidence that the muscles of ME/cfs patients have trouble utilizing the main sugar used for energy in the body. Could there be a genetic/epigenetic component?

Epigenetics:

Our DNA can be “methylated” to control different cellular programs in different types of cells. Can changes in this pattern of DNA methylation tell us anything about ME/cfs?

Metabolomics:

A diverse collaboration of ME/cfs researchers released a pre-print that confirmed previous findings of reduced phospholipids in patients! These phospholipids are essential for the health of the nervous system and for mitochondria.

The hypothalamus:

Dr. John Richardson was an early ME/cfs researcher who felt that many symptoms originated in the hypothalamus, a part of the brain that controls hormones in the body. More recently, Dr. Warren Tate has postulated that there is neuroinflammation in the hypothalamus. Phoenix Rising member Andyguitar ponders “Is our hypothalamus up the creek?”

Micro-RNA:

Micro-RNA’s are normal RNA molecules that the cell makes to inhibit the production of certain proteins. Researchers are trying to see if specific micro-RNAs (miRNA) are correlated with specific diagnoses. If they are, the correlation might lead to a diagnostic test for ME/cfs!

Extracellular vesicles:

A “vesicle” is like a bubble. It is surrounded by a fatty membrane and is filled with water and other things. An “extracellular vesicle” is any vesicle that is found in the body outside any cell. An extracellular vesicle can contain proteins, micro-RNA’s, cytokines, viruses, and lots of other things. Can studies about extracellular vesicles teach us anything about ME/cfs?

Tarlov cysts:

A Tarlov Cyst is an abnormal fluid-filled pocket where a sensory nerve meets the spinal cord. It can alter sensations such as touch or pain. A recent study that looked at Fibromyalgia and ME/cfs patients reported that 39% had a Tarlov cyst.

Meet the Researchers: PolyBio Research Initiative

A brand-new research initiative from a coalition of some of the brightest young minds in ME/cfs research! Meet Dr. Michael VanElzakker and Dr. Amy Proal.

Meet the Doctor: Byron Hyde

From investigating the early outbreaks of ME/cfs to organizing the first world-wide conference on ME/cfs research, Dr. Byron Hyde was standing up for patients from the very beginning. If you’re not familiar with Dr. Byron Hyde’s nearly 40 years of ME/cfs advocacy, hear from him in his own words.

Meet the Scientist: Lucinda Bateman

Dr. Lucinda Bateman has treated over 1000 ME/cfs patients since 2000, served on a IOM expert committee, & has an upcoming documentary called Relevium. Phoenix Rising member Bronc interviewed her.

Meet the Scientist: Ronald Tompkins

Dr. Ronald Tompkins was Professor at Harvard Medical School, Chief Medical Officer of Open Medicine Foundation, & had over 450 papers published in scientific journals. Phoenix Rising member Bronc interviewed him.

Meet the Scientist: Dane Cook

Dane Cook is Professor of Kinesiology & member of NINDS Advisory Council on ME/cfs. He researches how exercise challenges affect central, autonomic & immune systems. Phoenix Rising member Bronc interviewed him.

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