Active Transposable Elements in Immune Cells Can Lead to Flu-Like Symptoms in Fibromyalgia, Study Finds

Active Transposable Elements in Immune Cells Can Lead to Flu-Like Symptoms in Fibromyalgia, Study Finds

Active transposable elements — small DNA fragments that can change position within the genome — found in immune cells of women with fibromyalgia can increase the levels of certain immune proteins, and be the reason why some patients experience flu-like symptoms, a study suggests.

The study, “Activation of Transposable Elements in Immune Cells of Fibromyalgia Patients,” was published in the International Journal of Molecular Sciences.

People with fibromyalgia frequently have myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a condition characterized by overwhelming fatigue that is not alleviated by rest. 

While both fibromyalgia and ME/CFS share common features, including abnormal immune function and infectious flu-like symptoms, no clear connection with viral infections has been found. 

In 2019, a team of investigators at the Universidad Católica de Valencia San Vicente Mártir, in Spain, found the activation of transposable elements (TEs) that constantly change position within the genome (all genes in our DNA) might trigger flu-like symptoms in ME/CFS patients in the absence of an infection.

These findings were supported by work from another group of researchers who found TEs called human endogenous retrovirus K (HERV-K) were highly active in patients with ME/CFS. HERVs are DNA leftovers from retroviral infections and their dysregulation has been linked to several neurologic and autoimmune diseases.

These findings prompted the team in Spain to investigate if HERVs could also be involved in the flu-like symptoms seen in patients with fibromyalgia.

To find out, they collected blood samples from 14 women with fibromyalgia, ages 42–65, and 14 healthy women (controls), ages 38–65, to isolate peripheral blood mononuclear cells (PBMCs). PBMCs are immune cells found in the blood, namely T-cells, B-cells, and natural killer cells.

Eleven women had lived with fibromyalgia for more than three years, and six for more than 12 years. Half of the patients also had ME/CFS. All patients stopped taking their routine medications 12 hours prior to having their blood drawn for analysis. 

Afterwards, investigators isolated RNA from PBMCs and used a technique called quantitative real-time polymerase chain reaction to measure and compare the expression levels (activity) of three TEs — HERV-H, HERV-K and HERV-W — between the two groups of women.

The analysis revealed that all three HERV TEs were highly active in immune cells isolated from women with fibromyalgia compared to controls. 

To explore the possible effects of these TEs on immune cells, the researchers measured the levels of two immune markers: interferons (INF), which are proteins produced in response to viral infections, and tumor necrosis alpha (TNF-alpha), a protein involved in systemic inflammation. 

They found that in patients where HERVs were very active, the levels of two types of interferons — INF-beta and INF-gamma — were also high.

Positive correlations were identified between HERV-H and INF-beta, as well as between HERV-W, INF-beta, and INF-gamma. While TNF-alpha levels tended to be higher in women with fibromyalgia, the difference was not significant compared to controls. 

According to the authors, “this is the first study to report increased expression of HERV-K, HERV-H, HERV-W and INF-beta and INF-gamma levels correlations, in the immune system of FM [fibromyalgia] patients. The findings reported in this study could explain the flu-like symptoms FM patients present within clinical practice, in the absence of concomitant infections.”

“Future work aimed at identifying specific genomic loci [locations] differentially affected in FM and/or ME/CFS is warranted,” they added.