Gene Expression Profiling in Fibromyalgia Indicates an Autoimmune Origin of the Disease and Opens New Avenues for Targeted Therapy
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...
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MDPI AG
2020-06-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/9/6/1814 |
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| author | Marzia Dolcino Elisa Tinazzi Antonio Puccetti Claudio Lunardi |
| author_facet | Marzia Dolcino Elisa Tinazzi Antonio Puccetti Claudio Lunardi |
| author_sort | Marzia Dolcino |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T19:14:51Z |
| format | Article |
| id | doaj.art-421890f6d43e4eaf9bfc5834735a97ff |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T19:14:51Z |
| publishDate | 2020-06-01 |
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| series | Journal of Clinical Medicine |
| spelling | doaj.art-421890f6d43e4eaf9bfc5834735a97ff2023-11-20T03:27:17ZengMDPI AGJournal of Clinical Medicine2077-03832020-06-0196181410.3390/jcm9061814Gene Expression Profiling in Fibromyalgia Indicates an Autoimmune Origin of the Disease and Opens New Avenues for Targeted TherapyMarzia Dolcino0Elisa Tinazzi1Antonio Puccetti2Claudio Lunardi3Department of Medicine, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, ItalyDepartment of Medicine, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, ItalyDepartment of Experimental Medicine, Section of Histology, University of Genova, Via G.B. Marsano 10, 16132 Genova, ItalyDepartment of Medicine, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, ItalyFibromyalgia 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.https://www.mdpi.com/2077-0383/9/6/1814fibromyalgialong non-coding RNAsignaling pathwayprotein-protein (PPI) networkgene module |
| spellingShingle | Marzia Dolcino Elisa Tinazzi Antonio Puccetti Claudio Lunardi Gene Expression Profiling in Fibromyalgia Indicates an Autoimmune Origin of the Disease and Opens New Avenues for Targeted Therapy Journal of Clinical Medicine fibromyalgia long non-coding RNA signaling pathway protein-protein (PPI) network gene module |
| title | Gene Expression Profiling in Fibromyalgia Indicates an Autoimmune Origin of the Disease and Opens New Avenues for Targeted Therapy |
| title_full | Gene Expression Profiling in Fibromyalgia Indicates an Autoimmune Origin of the Disease and Opens New Avenues for Targeted Therapy |
| title_fullStr | Gene Expression Profiling in Fibromyalgia Indicates an Autoimmune Origin of the Disease and Opens New Avenues for Targeted Therapy |
| title_full_unstemmed | Gene Expression Profiling in Fibromyalgia Indicates an Autoimmune Origin of the Disease and Opens New Avenues for Targeted Therapy |
| title_short | Gene Expression Profiling in Fibromyalgia Indicates an Autoimmune Origin of the Disease and Opens New Avenues for Targeted Therapy |
| title_sort | gene expression profiling in fibromyalgia indicates an autoimmune origin of the disease and opens new avenues for targeted therapy |
| topic | fibromyalgia long non-coding RNA signaling pathway protein-protein (PPI) network gene module |
| url | https://www.mdpi.com/2077-0383/9/6/1814 |
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