Gene Expression Profiling in Fibromyalgia Indicates an Autoimmune Origin of the Disease and Opens New Avenues for Targeted Therapy

Overview

Journal J Clin Med

Specialty General Medicine

Date 2020 Jun 14

PMID 32532082

Citations 16

Authors

Marzia Dolcino

Elisa Tinazzi

Antonio Puccetti

Claudio Lunardi

Affiliations

Soon will be listed here.

Abstract

Fibromyalgia is a chronic disorder characterized by widespread pain and by several non-pain symptoms. Autoimmunity, small fiber neuropathy and neuroinflammation have been suggested to be involved in the pathogenesis of the disease. We have investigated the gene expression profile in peripheral blood mononuclear cells obtained from ten patients and ten healthy subjects. Of the 545,500 transcripts analyzed, 1673 resulted modulated in fibromyalgic patients. The majority of these genes are involved in biological processes and pathways linked to the clinical manifestations of the disease. Moreover, genes involved in immunological pathways connected to interleukin-17 and to Type I interferon signatures were also modulated, suggesting that autoimmunity plays a role in the disease. We then aimed at identifying differentially expressed Long non-coding RNAs (LncRNAs) functionally connected to modulated genes both directly and via microRNA targeting. Only two LncRNAs of the 298 found modulated in patients, were able to target the most highly connected genes in the fibromyalgia interactome, suggesting their involvement in crucial gene regulation. Our gene expression data were confirmed by real time PCR, by autoantibody testing, detection of soluble mediators and Th-17 polarization in a validation cohort of 50 patients. Our results indicate that genetic and epigenetic mechanisms as well as autoimmunity play a pivotal role in the pathogenesis of fibromyalgia.

Citing Articles

Management of Fibromyalgia: Novel Nutraceutical Therapies Beyond Traditional Pharmaceuticals.

Antonelli A, Bianchi M, Fear E, Giorgi L, Rossi L Nutrients. 2025; 17(3).

PMID: 39940388 PMC: 11820827. DOI: 10.3390/nu17030530.

Role of Vitamin D Status and Alterations in Gut Microbiota Metabolism in Fibromyalgia-Associated Chronic Inflammatory Pain.

Saija C, Bertuccio M, Scoglio A, Macaione V, Cacciola F, Micalizzi G Biomedicines. 2025; 13(1).

PMID: 39857723 PMC: 11760899. DOI: 10.3390/biomedicines13010139.

Electroacupuncture Reduced Fibromyalgia-Pain-like Behavior through Inactivating Transient Receptor Potential V1 and Interleukin-17 in Intermittent Cold Stress Mice Model.

Yeh Y, Liao H, Hsiao I, Hsu H, Lin Y Brain Sci. 2024; 14(9).

PMID: 39335365 PMC: 11430684. DOI: 10.3390/brainsci14090869.

Inflammation, Autoimmunity, and Infection in Fibromyalgia: A Narrative Review.

Paroli M, Gioia C, Accapezzato D, Caccavale R Int J Mol Sci. 2024; 25(11).

PMID: 38892110 PMC: 11172859. DOI: 10.3390/ijms25115922.

Identification of unique genomic signatures in patients with fibromyalgia and chronic pain.

Mohapatra G, Dachet F, Coleman L, Gillis B, Behm F Sci Rep. 2024; 14(1):3949.

PMID: 38366049 PMC: 10873305. DOI: 10.1038/s41598-024-53874-8.

References

Axtell R, de Jong B, Boniface K, van der Voort L, Bhat R, De Sarno P . T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis. Nat Med. 2010; 16(4):406-12. PMC: 3042885. DOI: 10.1038/nm.2110. View

Salaffi F, Di Carlo M, Farah S, Atzeni F, Buskila D, Ablin J . Diagnosis of fibromyalgia: comparison of the 2011/2016 ACR and AAPT criteria and validation of the modified Fibromyalgia Assessment Status. Rheumatology (Oxford). 2020; 59(10):3042-3049. DOI: 10.1093/rheumatology/keaa061. View

Boerma T, Harrison J, Jakob R, Mathers C, Schmider A, Weber S . Revising the ICD: explaining the WHO approach. Lancet. 2016; 388(10059):2476-2477. DOI: 10.1016/S0140-6736(16)31851-7. View

Pathan M, Keerthikumar S, Ang C, Gangoda L, Quek C, Williamson N . FunRich: An open access standalone functional enrichment and interaction network analysis tool. Proteomics. 2015; 15(15):2597-601. DOI: 10.1002/pmic.201400515. View

Sarzi-Puttini P, Atzeni F, Masala I, Salaffi F, Chapman J, Choy E . Are the ACR 2010 diagnostic criteria for fibromyalgia better than the 1990 criteria?. Autoimmun Rev. 2017; 17(1):33-35. DOI: 10.1016/j.autrev.2017.11.007. View

Carvalho L, Correa H, Silva G, Campos F, Baiao F, Ribeiro L . May genetic factors in fibromyalgia help to identify patients with differentially altered frequencies of immune cells?. Clin Exp Immunol. 2008; 154(3):346-52. PMC: 2633236. DOI: 10.1111/j.1365-2249.2008.03787.x. View

Ashburner M, Ball C, Blake J, Botstein D, Butler H, Cherry J . Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000; 25(1):25-9. PMC: 3037419. DOI: 10.1038/75556. View

Banfi G, Diani M, Pigatto P, Reali E . T Cell Subpopulations in the Physiopathology of Fibromyalgia: Evidence and Perspectives. Int J Mol Sci. 2020; 21(4). PMC: 7072736. DOI: 10.3390/ijms21041186. View

Lichtenstein A, Tiosano S, Amital H . The complexities of fibromyalgia and its comorbidities. Curr Opin Rheumatol. 2017; 30(1):94-100. DOI: 10.1097/BOR.0000000000000464. View

10.

Bair M, Krebs E . Fibromyalgia. Ann Intern Med. 2020; 172(5):ITC33-ITC48. DOI: 10.7326/AITC202003030. View

11.

Dolcino M, Tinazzi E, Puccetti A, Lunardi C . In Systemic Sclerosis, a Unique Long Non Coding RNA Regulates Genes and Pathways Involved in the Three Main Features of the Disease (Vasculopathy, Fibrosis and Autoimmunity) and in Carcinogenesis. J Clin Med. 2019; 8(3). PMC: 6462909. DOI: 10.3390/jcm8030320. View

12.

Cline M, Smoot M, Cerami E, Kuchinsky A, Landys N, Workman C . Integration of biological networks and gene expression data using Cytoscape. Nat Protoc. 2007; 2(10):2366-82. PMC: 3685583. DOI: 10.1038/nprot.2007.324. View

13.

Dolcino M, Ottria A, Barbieri A, Patuzzo G, Tinazzi E, Argentino G . Gene Expression Profiling in Peripheral Blood Cells and Synovial Membranes of Patients with Psoriatic Arthritis. PLoS One. 2015; 10(6):e0128262. PMC: 4473102. DOI: 10.1371/journal.pone.0128262. View

14.

Bazzichi L, Giacomelli C, Consensi A, Giorgi V, Batticciotto A, Di Franco M . One year in review 2020: fibromyalgia. Clin Exp Rheumatol. 2020; 38 Suppl 123(1):3-8. View

15.

Dolcino M, Pelosi A, Fiore P, Patuzzo G, Tinazzi E, Lunardi C . Long Non-Coding RNAs Play a Role in the Pathogenesis of Psoriatic Arthritis by Regulating MicroRNAs and Genes Involved in Inflammation and Metabolic Syndrome. Front Immunol. 2018; 9:1533. PMC: 6054935. DOI: 10.3389/fimmu.2018.01533. View

16.

Mi H, Muruganujan A, Casagrande J, Thomas P . Large-scale gene function analysis with the PANTHER classification system. Nat Protoc. 2013; 8(8):1551-66. PMC: 6519453. DOI: 10.1038/nprot.2013.092. View

17.

Arnold L, Bennett R, Crofford L, Dean L, Clauw D, Goldenberg D . AAPT Diagnostic Criteria for Fibromyalgia. J Pain. 2018; 20(6):611-628. DOI: 10.1016/j.jpain.2018.10.008. View

18.

Fitzcharles M, Ste-Marie P, Goldenberg D, Pereira J, Abbey S, Choiniere M . 2012 Canadian Guidelines for the diagnosis and management of fibromyalgia syndrome: executive summary. Pain Res Manag. 2013; 18(3):119-26. PMC: 3673928. DOI: 10.1155/2013/918216. View

19.

Fitzcharles M, Perrot S, Hauser W . Comorbid fibromyalgia: A qualitative review of prevalence and importance. Eur J Pain. 2018; 22(9):1565-1576. DOI: 10.1002/ejp.1252. View

20.

Ambrosi A, Espinosa A, Wahren-Herlenius M . IL-17: a new actor in IFN-driven systemic autoimmune diseases. Eur J Immunol. 2012; 42(9):2274-84. DOI: 10.1002/eji.201242653. View