The Roles of Autoimmunity and Inflammation in Chronic Fatigue Syndrome

Chronic fatigue syndrome (CFS), also described as myalgic encephalomyelitis (ME) is considered an immune-mediated disorder. It has long been considered a "mystery illness," but that viewpoint is becoming dated. 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 and Harmful

Inflammation is involved in many illnesses and injuries, and most adults have used at least one anti-inflammatory drug in their lifetime. We routinely ice and elevate our injuries to keep them from getting too inflamed.

We usually view inflammation as a problem--a symptom to be treated. However, inflammation is part of a healthy response to problems in the body. When your body detects a problem—whether it be invading viruses or bacteria, or tissues damaged from injury—the immune system triggers an inflammatory response.

What happens during an inflammatory response is that blood vessels dilate to deliver more blood to the injured area, and immune proteins are released into that blood. White blood cells flow out of the blood vessels into the problem area to kill or clean up materials 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.

Ongoing damage can come from something like back pain from an injury that's aggravated by poor posture, or repeated damage due to disease. When that damage is due to a misfiring immune system, it can mean autoimmunity.

Autoimmunity: The System Misfires

Autoimmunity is when the immune system mistakenly identifies a part of your body as a foreign invader, like a virus it needs to get rid of. Your own body triggers its inflammatory process and sends specialized cells to destroy the target and begin the healing process.

Only with autoimmunity, the healing process creates more of whatever body part your immune system doesn't like, so it continues to attack. And heal. And attack. And the process continues indefinitely.

Autoimmunity is a specific type of immune-system dysfunction, but it's important to note that not all immune-system dysfunction is autoimmunity.

ME/CFS: What Do We Know?

Researchers have long believed that ME/CFS could involve 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, the 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 published in Psychiatry Research attempted to separate chronic fatigue, chronic fatigue syndrome, and myalgic encephalitis into different categories. Researchers found that ME patients had higher levels of two specialized immune proteins called cytokines, which promote inflammation. They're called interleukin-1 and tumor necrosis factor-alpha. They also found elevated levels of neopterin, which is an indicator of pro-inflammatory immune activity.

More recently, studies have shown that inflammatory markers can accurately distinguish ME/CFS from depression or sickness behaviors.

A study published in Metabolic Brain Disease is just one of a growing body considering oxidative and nitrosative stress coupled with low antioxidant levels as a possible mechanism of ME/CFS, suggesting that these factors could point to an immuno-inflammatory pathology.

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 In Vivo 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 in Molecular Neurobiology 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 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 processes that could 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 begins attacking it. Essentially, because both cells look similar, the immune system labels them as identical, when in fact one type actually belongs in your body.

In bystander activation:

• The body is attacked by a virus
• The immune system responds by activating specialized cells
• That activation mistakenly 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 serotonin (5-HT). 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 healthcare provider to determine the nature of your specific case of ME/CFS and how best to treat it.