Immune System May Play Role in Fibromyalgia, Study Suggests

Immune System May Play Role in Fibromyalgia, Study Suggests
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Through a new genetic analysis, researchers have found evidence suggesting the involvement of the immune system in fibromyalgia (FM), a study reports.

Inherited mutations in genes that provide instructions for the production of three immune molecules — called CCL11, CCL4 and MEFV — impact the immune system and may be associated with the risk of fibromyalgia, according to the researchers.

The study, “SNPs in inflammatory genes CCL11CCL4 and MEFV in a fibromyalgia family study,” waa published in the journal Plos One.

Previous family studies have suggested a genetic component linked to fibromyalgia, with several pieces of evidence pointing to a role for genes involved in inflammatory pathways.

In another study, researchers found that the levels of several inflammatory chemokines — proteins secreted by cells — were elevated in fibromyalgia.

Among these were the chemokines CCL11 and CCL4, located in a chemokine gene cluster in chromosome 17, which is associated with immune-related disorders, including atopic dermatitis and inflammatory bowel disease (IBD).

Researchers in this study performed a sequencing analysis of the chemokine gene cluster identified in chromosome 17 in 100 fibromyalgia patients. Their DNA was extracted from blood immune cells, called lymphocytes, or saliva. The same analysis was performed in the DNA from unrelated, gender and age- matched individuals used as controls.

Researchers focused their analysis on single nucleotide polymorphisms, or SNPs, which are variations of single nucleotides — the building blocks of the DNA sequence.

The analysis first revealed a total of 4,332 SNPs, but to shorten this list, the researchers proceeded to analyze those occurring in at least 10% of the 100 fibromyalgia patients. A total of 413 SNPs met this criteria.

“Based on the hypothesis that FM has an immune component, we further selected only those SNPs found in the chromosome 17 cluster of 18 chemokine genes,” the researchers wrote.

They identified only four SNPs in four chemokine genes — CCL11, CCL8, CCL23 and CCL4 — which were further studied.

They analyzed the transmission of the four SNPs from parents to fibromyalgia patients, and only one of them in the CCL11 gene, called rs1129844, was significant, meaning it was associated with a risk of the disease. Among a group of 220 fibromyalgia patients, researchers identified 36.8% who had at least one copy of this SNP.

Researchers performed further analysis to understand the effects of this variant, and found it affected the normal production of the CCL11 protein. They noted, however, that the levels of CCL11 protein are statistically higher in most of fibromyalgia patients.

“While the elevated expression of CCL11 is a common event, the inability to generate a robust CCL11 response predisposes up to 36% of patients with a higher likelihood of FM,” they wrote.

They currently have no explanation for this phenomenon, but argue that although further studies are necessary to validate these findings, this SNP may be used as a marker of fibromyalgia risk.

“This study provides evidence that rs1129844 in CCL11 may be a useful marker for FM and that the high frequency of this SNP in FM patients (36.8%) argues for an underlying immune connection,” they said.

The levels of another chemokine, CCL4, were also decreased in the SNP variant of CCL1 compared with controls, suggesting a possible relationship between the two chemokines and their variants, and that both chemokines are involved in fibromyalgia.

Morever, researchers found several variants in the MEFV gene, which provides instructions for a protein called pyrin, with a significant transmission bias. This protein’s function is still not fully understood, but research suggests it is likely to help keep inflammation under control, which provides another link supporting the role of the immune system in fibromyalgia.

“Considering that activation of the immune system is often associated with neurological systems such as pain, the involvement of the immune system in FM does not rule out the prevailing hypothesis that FM is predominantly a pain syndrome,” the researchers wrote.

“With this in mind, further studies on larger number of patients may help to validate the link between pain and the immune system in FM,” the study concluded.

Patricia holds a Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She has also served as a PhD student research assistant at the Department of Microbiology & Immunology, Columbia University, New York.
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Patricia holds a Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She has also served as a PhD student research assistant at the Department of Microbiology & Immunology, Columbia University, New York.
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