VeryWell blog post, by Adrienne Dellwo [Reviewed by a board-certified physician], 8 July 2016: Is Chronic Fatigue Syndrome Autoimmune & Inflammatory?

What We Know About It
You still hear that chronic fatigue syndrome (ME/CFS) is a “mystery illness,” but the nature and mechanisms of the disease are beginning to take shape, thanks to the ongoing efforts of researchers. Over the years, especially recent ones, we’ve learned a huge amount. Some of that knowledge points to roles that inflammation and autoimmunity may play in this illness.

To understand the research, it helps to know a little about the processes themselves.

Inflammation: Helpful & Harmful

We all know that inflammation is involved in many illnesses and injuries, and it’s rare to find a house that doesn’t contain at least one anti-inflammatory drug. We ice and elevate our injuries, to keep them from getting too inflamed.

However, it might surprise you to learn that inflammation is part of a healthy response to problems in the body. When your system detects a problem—whether it be an invading virus or bacteria, or tissues damaged from injury—it triggers an inflammatory response.

What happens is that blood vessels dilate to get more blood to the area, and extra protein is pumped into that blood. White blood cells move from the blood vessels into the problem area and kill or clean up anything that shouldn’t be there. Then the tissue can begin to heal.

So when you bash your shin or twist an ankle, a little swelling is a good thing. It means the healing process is at work.

On the other hand, when inflammation becomes chronic due to ongoing damage or a misfiring immune system, then you’ve got a problem.

An example of ongoing damage can be something like back pain from an injury that’s aggravated by poor posture, or repeated damage due to disease. A misfiring immune system can mean autoimmunity.

Autoimmunity: The System Misfires

In autoimmunity, the body is suffering from friendly fire. The immune system has gone haywire and now identifies a part of your body as a foreign invader. It then triggers the inflammatory process and sends in specialized cells to destroy the target and begin the healing process.

Only now, the healing process creates more of whatever body part your immune system doesn’t like, so the process continues indefinitely.

It’s important to note that not all immune-system dysfunction is autoimmune.

ME/CFS: What Do We Know?

Researchers have long believed ME/CFS involved chronic inflammation. Studies reveal several biomarkers of inflammation and a sustained immune response in the blood of ME/CFS patients. Some researchers now consider ME/CFS to be a neuroimmune or neuroendocrineimmune disease.

However, we’re still learning about the specific role of inflammation in the condition. Recent research paints a growing picture of autoimmunity as well. And when autoimmunity is involved, a major question is: what is its target?

Possible Causes of Inflammation

Much of the ME/CFS research community takes inflammation as a given. In the alternative name myalgic encephalitis (ME), which has been adopted by some researchers, encephalitis means inflammation of the brain and spinal cord.

Some researchers point to possible inflammatory triggers that don’t involve autoimmunity.

A 2012 study attempting to separate chronic fatigue, chronic fatigue syndrome, and myalgic encephalitis into different categories found that ME patients had higher levels of the pro-inflammatory cytokines interleukin-1 and tumor necrosis factor alpha as well as neopterin, which is an indicator of pro-inflammatory immune activity.

More recently, studies have shown that inflammatory markers can accurately distinguish the condition from depression or sickness behaviors.

A study published in Metabolic Brain Disease is just one of a growing body considering oxidative and nitrosative stress (O&NS) coupled with low antioxidant levels a possible mechanism of ME/CFS, saying these factors could point to an immuno-inflammatory pathology. (Learn more about this theory: Oxidative Stress & the Pall Protocol.)

Other researchers have suggested that certain pathogens may, in predisposed people, trigger a chronic immune activation, which would create chronic inflammation and a cascade of problems. One of the main suspects in this scenario is the Epstein-Barr virus, which causes mononucleosis (“the kissing disease.”)

A 2013 study investigated markers of retrovirus activity in the gut based on the theory that, through the brain-gut connection, a gut infection may lead to inflammation of the brain. Researchers did find some evidence, but this was a small, preliminary study and a lot of work remains to be done in this area.

The Case for Autoimmunity

Some researchers have found evidence suggesting ME/CFS is, at least in part, an autoimmune disease. A few different targets of a misfiring immune system have been suggested.

In a 2013 study examining the possible relationship of O&NS and autoimmunity, researchers said that the presence of pro-inflammatory cytokines and several other known dysfunctions associated with ME/CFS may predispose you to autoimmunity. That means autoimmune activity may be a consequence of the condition rather than a cause of it. These researchers suspect that constant viral infections may lead to a couple of theoretical processes that may induce autoimmunity: bystander activation and molecular mimicry.

In molecular mimicry, the immune system fights an infectious agent and then begins to confuse it with a similar cell in the body and therefore begins attacking it. Essentially, because both cells look like a duck, the immune system labels them both ducks, when in fact one is a goose, and the goose belongs in that ecosystem.

In bystander activation, the body is attacked by a virus, the immune system responds by activating specialized cells, and, for some reason, that activation mistakenly triggers a different type of specialized cell—an autoimmune cell—that begins attacking the body’s tissues.

In the same study, researchers also list several other methods by which ME/CFS may trigger autoimmunity, including dysfunction of mitochondria, which provide energy to your cells, and cellular damage caused by O&NS that cause your immune system to misidentify them.

A different 2013 study involving many of the same researchers puts forth the possibility of an autoimmune reaction to 5-HT, also known as serotonin. As a hormone and neurotransmitter, serotonin performs several crucial roles in both the gut and the brain. Serotonin dysregulation has long been believed to be involved in ME/CFS.

Researchers say that just over 60 percent of the participants with ME/CFS tested positive for autoimmune activity against 5-HT—more than 10 times the rate of the control group, and quadruple the rate of those with long-lasting fatigue that didn’t meet the criteria for ME/CFS.

Could Several Answers Be Right?

In the end, it could be that different cases of ME/CFS have different causes of inflammation, and that some cases are autoimmune while others are not. Remember that ME/CFS can be significantly different from one person to another. It may be that several different subgroups, and perhaps even different diseases, are currently lumped into one basket.

Scientists are still working to sort it all out. Meanwhile, you need to find ways to manage your condition. It’s important that you work with your doctor to determine the nature of your specific case of ME/CFS and how best to treat it.

Agliari E, et al. Journal of biological dynamics. 2012;6(2):740-62. Can persistent Epstein-Barr virus infection induce chronic fatigue syndrome as a Pavlov reflex of the immune response?
Arnett SV, Clark IA. Journal of Affective Disorders. 2012 Dec 10;141(2-3):130-42. Inflammatory fatigue and sickness behaviour -lessons for the diagnosis and management of chronic fatigue syndrome.

De Meirleir KL, et al. In Vivo. 2013 Mar-Apr;27(2):177-87. Plasmacytoid dendritic cells in the duodenum of individuals diagnosed with myalgic encephalomyelitis are uniquely immunoreactive to antibodies to human endogenous retroviral proteins.

Fujinami RS, et al. Clinical microbiology reviews. 2006 Jan;19(1):80-94. Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease.

Maes M, Ringel K, et al. Journal of affective disorders. 2013 Sep 5;150(2):223-30. In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation.

Maes M, Twisk FN, Johnson C. Psychiatry research. 2012 Dec 30;200(2-3):754-60. Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) are distinguished accurately: results of supervised learning techniques applied on clinical and inflammatory data.

Maes M, Twisk FN, Ringel K. Psychotherapy and psychosomatics. 2012;81(5):286-95. Inflammatory and cell-mediated immune biomarkers in myalgic encephalomyelitis/ chronic fatigue syndrome and depression: inflammatory markers are higher in myalgic encephalomyelitis/chronic fatigue syndrome than in depression.

Morris G, Anderson G, et al. BMC medicine. 2013 Mar 8;11:64. A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and sickness behavior.

Morris G, Berk M, et al. Molecular neurobiology. 2013 Sep 26. [Epub ahead of print] The ermerging role of autoimmunity in myalgic encephalomyelitis/chronic fatigue syndrome (me/cfs).

Morris G, Maes M. Metabolic brain disease. 2012 Jun 21. A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome.

This entry was posted in News and tagged , , , , , , , . Bookmark the permalink.

Comments are closed.