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Treatment & Research News

Is Fibro an Autoimmune Disease?

Could something in the blood be causing your fibromyalgia? Yes, according to a study headed up by Andreas Goebel, M.D., Ph.D., of Liverpool, UK and teams at King’s College London and Karolinska Institute in Stockholm/Sweden.* Their teams injected mice with serum from fibromyalgia patients and the mice developed widespread pain within two days. The immunoglobulin G (IgG) portion of the serum, which is loaded with antibodies, was found to be the pain-producing culprit. Serum without IgG had no impact.

Goebel hypothesized that fibromyalgia may have an autoimmune basis and that autoreactive IgG might be responsible for the symptoms. But how could this occur in the absence of tissue damage that normally exists in autoimmune diseases? Goebel says the antibodies could be attacking the sensory nerves or nearby cells, which could lead to amplified signals traveling to the spinal cord.

In the serum-injected mice, the IgG antibodies were clustered around special immune cells called satellite glial cells or SGCs. As shown in Figure 1, the SCGs enclose the cell bodies of the peripheral nerves and can ramp up the signal just before it enters the spinal cord. In addition, the chemicals secreted by the SGCs can influence the cerebral spinal fluid (which bathes the cord and brain) to cause more havoc.

Having pain all over without any signs of tissue destruction or a blood test to prove its existence is a credibility nightmare for fibromyalgia patients. Yet, all Goebel had to do was inject fibromyalgia serum into mice to cause pain, reduced activity (sign of fatigue?), sensitivity to cold, and reduced grip strength. Injecting serum from healthy subjects did not produce symptoms.

“Antibody-mediated immune processes in chronic primary pain (such as fibromyalgia) have been hiding in plain sight,” says Goebel, adding that they are invisible to standard laboratory tests. He also challenges the traditional assumption that the degree of tissue destruction should correlate to the patient’s level of pain or quality of life. 

Injecting serum from patients into rodents to see if the symptoms can be reproduced is called a passive transfer study and it’s been done in other medical conditions. Although the current project involved patients from two different centers (one in the UK and the other in Sweden), the findings still need to be independently confirmed. Fortunately, at least two research teams are working to replicate Goebel’s results. 

One last point: people are not mice. So how do the researchers know the SGCs are the cells under attack in humans? Goebel and his colleagues have incubated the IgG from fibromyalgia patients and healthy controls with SGCs taken from seven post-mortem subjects (none had fibromyalgia). Using a fluorescent dye and electron microscopy, the SGCs were heavily coated with IgG from fibromyalgia patients. It’s as though the fibromyalgia IgG is drawn to the SGCs like iron to a magnet.

Game Changer for Fibromyalgia

If Goebel’s work stands the test of time, fibromyalgia would be an autoantibody type of pain. This could be a game changer for fibromyalgia research because the condition is currently viewed as a dysfunctional central nervous system. Although plenty of evidence shows the brain and spinal cord do not operate properly, the cause remains unknown. However, if antibodies are attacking the SGCs, this could be the autoimmune trigger that causes the nervous system commotion.

Research has pointed to multiple abnormalities in the central nervous system. The spinal cord contains too many pain messengers and not enough soothers. The pain control system doesn’t work, and the brain centers don’t provide a united front to contain the barrage of noxious impulses. Sleep is disrupted, hormones are dysregulated, and cognitive functions are diminished.

The foregoing findings have been packaged into the central sensitization theory to explain pain without a triggering source. It assumes that the central nervous system is hypersensitized to incoming sensory signals, but no one knows why. This, in turn, leads to an abnormally exaggerated response. In the case of fibromyalgia, a harmless trickle of nerve impulses might be transformed into widespread pain and other symptoms.

“Some say you don’t need a driving source to sustain central sensitization,” says Goebel, “but it has never been shown convincingly in any animal model. That’s why many of us (physicians and researchers) never really believed it.”

IgG autoreactive antibodies clustered around the SGCs may provide the missing piece to the fibromyalgia puzzle. As shown in Figure 2, activated SGCs form a pain-generating circuitry up and down both sides of the spinal cord (each red dot represents thousands of SGC/neuron units). Hurting from head to toe would be expected, not questioned! The spinal cord and brain would naturally be thrown into turmoil.   

Study Implications

Wondering why your body is generating antibodies that attack the SGCs? Examining the mice won’t answer this question. “Our model takes it from the point where the IgG antibodies are already produced,” says Goebel. However, trying to dissect the tiny fraction of the IgG that is pathogenic (autoreactive) could lead to a disease marker and Goebel’s colleagues in Sweden are working on this.

What about better treatments? As the IgG works its way out of the mouse’s body, the symptoms go away. So, approaches that reduce the IgG attachment to the SGCs should work, even if they do not stop the ongoing production of autoreactive IgG antibodies. Currently, therapies in this category are extremely expensive and not available to fibromyalgia patients.

Alternatively, tempering the SGC activation that leads to amplification of the sensory signals might work to reduce fibromyalgia symptoms. For example, low dose naltrexone targets specific receptors on the SGCs to quiet them down. It’s not likely to be as effective as approaches aimed at dislodging the harmful IgG from the SGCs, but it is cheap and readily available.

Presuming autoantibodies to your SGCs are driving your symptoms, this could explain why medications that work in the spinal cord produce dismal results. Examples include the three FDA-approved drugs (pregabalin, duloxetine, and Savella) that operate downstream of the SGCs. Using them could be the equivalent to putting a bucket under a leaky faucet, while targeting the SGCs would be more akin to repairing the faucet.

Bottom Line

Once Goebel’s work is replicated and the word spreads about the passive transfer study, fibromyalgia patients will finally have something they have long deserved: credibility. The mouse model using fibromyalgia IgG will help researchers identify the physiological mechanisms and develop more effective treatments. It could be a long road ahead, but at least research will be moving in the right direction.

*  Goebel A, Krock E, Gentry C, et al., 2021. Passive transfer of fibromyalgia symptoms from patients to mice. J Clin Invest. 131(13):e144201.