Autoantibodies: a possible contributor to fibromyalgia

Researchers at Karolinska Institutet and their British colleagues have identified a possible contributory cause of fibromyalgia, a difficult to treat pain condition. In a study on mice and human tissue, the researchers found that fibromyalgia patients’ antibodies played a key part in symptom development. The results, which are published in The Journal of Clinical Investigation, pave the way for developing new treatment strategies.

Camilla Svensson

Camilla Svensson. Photo: Ulf Sirborn

“Our study suggests that there is an autoimmune component to the symptomatology of patients with fibromyalgia and that these patients’ antibodies bind to glial cells that are part of the peripheral nervous system,” says Camilla Svensson, professor at the Department of Physiology and Pharmacology, Karolinska Institutet, and one of the paper’s corresponding authors. “This is an important discovery that calls into question the traditional view of fibromyalgia as a disease of the central nervous system only.”

Fibromyalgia affects an estimated 2 to 4 percent of the Swedish population, and the vast majority of patients are women. The condition is characterised by persistent tenderness, chronic fatigue, insomnia and enhanced sensitivity to pain. People with fibromyalgia can be hypersensitive to cold and often experience pain from stimuli that others deem painless.

No effective medical treatment

Despite the fact that the syndrome has been studied since the early 1900s, there is still no effective medical treatment for most patients with fibromyalgia. It is also quite common for sufferers to be met with ignorance and suspicion from others, including medical professionals.

The causes of the disease are largely unknown. Earlier studies have shown that changes in how pain signals are processed in the central nervous system are involved and that people with fibromyalgia have elevated levels of certain inflammatory substances in the cerebrospinal fluid. Research has also shown that more than half of those affected have increased activity in the thin pain nerve fibres and fewer nerve fibres in the skin.

In this current study, the researchers wanted to investigate if the immune system was a possible causal factor of the disease symptoms, given that the disease is more common in people with autoimmune diseases (i.e. diseases in which the immune cells produce autoantibodies to one’s own body).

Mice became more sensitive

The researchers isolated antibodies from patients with fibromyalgia and healthy controls and injected them into mice. They then tested the sensitivity of the mice by assessing the lowest pressure and temperature at which they would either flinch or withdraw their paw. The researchers found that mice with fibromyalgia antibodies became more sensitive than those that had received control antibodies. They also moved less than the other mice, had less muscle strength in their paws and had a reduced number of nerve fibres in the skin.

In studies on human tissue and cultured cells, the researchers also identified which cells the autoantibodies likely operate through. They discovered that the fibromyalgia antibodies bind to satellite glial cells, a type of cell that enwraps the neuron cell bodies in the parts of the peripheral nervous system called dorsal root ganglia (sensory nerve clusters along the spinal column). The antibodies from the fibromyalgia patients increased the activity of satellite glial cells in mice, unlike the control antibodies, and bound to these cells in human dorsal root ganglia.

Can lead to new therapies

“Our results open up the possibility of identifying individuals with fibromyalgia who have ‘problem antibodies’ and studying if already approved drugs that reduce antibody production or modulate the immune system in other ways can mitigate the symptoms of fibromyalgia,” Camilla Svensson says.

The study was conducted with researchers at King’s College London and the University of Liverpool in the UK, and included antibodies from patients with fibromyalgia from both Sweden and the UK.

The study was supported by grants from the Knut and Alice Wallenberg Foundation, a donation from the Lundblad Family for clinical pain research at Karolinska Institutet, the Swedish Research Council, Karolinska Institutet, Region Stockholm, the European Union, the International Association for the Study of Pain (IASP), the Canadian Institutes of Health Research, the King Gustaf V 80-year Foundation, the British Medical Research Council, Versus Arthritis, the Pain Relief Foundation and Eli Lilly & Co. One of the authors, David Andersson, has declared a conflict of interest in the form of financial support from Eli Lilly. No other conflicts of interest have been reported.

Publication

“Passive transfer of fibromyalgia symptoms from patients to mice,” *Andreas Goebel, *Emerson Krock, Clive Gentry, Mathilde R. Israel, Alexandra Jurczak, Carlos Morado Urbina, Katalin Sandor,Nisha Vastani, Margot Maurer, Ulku Cuhadar, Serena Sensi, Yuki Nomura, Joana Menezes, Azar Baharpoor, Louisa Brieskorn, Angelica Sandström, Jeanette Tour, Diana Kadetoff, Lisbet Haglund, Eva Kosek, Stuart Bevan, *Camilla I. Svenssonand *David A. Andersson, Journal of Clinical Investigation, online 1 July, 2021, doi: 10.1172/JCI144201 (*co-first/last authors)

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