Activation of Transposable Elements in Immune Cells of Fibromyalgia Patients

Abstract

Advancements in nucleic acid sequencing technology combined with an unprecedented availability of metadata have revealed that 45% of the human genome constituted by transposable elements (TEs) is not only transcriptionally active but also physiologically necessary. Dysregulation of TEs, including human retroviral endogenous sequences (HERVs) has been shown to associate with several neurologic and autoimmune diseases, including Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, no study has yet addressed whether abnormal expression of these sequences correlates with fibromyalgia (FM), a disease frequently comorbid with ME/CFS. The work presented here shows, for the first time, that, in fact, HERVs of the H, K and W types are overexpressed in immune cells of FM patients with or without comorbid ME/CFS. Patients with increased HERV expression (N = 14) presented increased levels of interferon (INF-β and INF-γ) but unchanged levels of TNF-α. The findings reported in this study could explain the flu-like symptoms FM patients present with in clinical practice, in the absence of concomitant infections. Future work aimed at identifying specific genomic loci differentially affected in FM and/or ME/CFS is warranted.

DNA Methylation Changes in Fibromyalgia Suggest the Role of the Immune-Inflammatory Response and Central Sensitization

“…In chronic fatigue syndrome, differentially methylated [ 45 ] and differentially expressed genes related to the immune response [ 46 , 47 ] were identified. A recent study also showed specific transposable elements overexpressed in the immune cells of FM patients [ 48 ]. Taken as a whole, these studies, together with our finding, appear to support a possible immune system dysregulation in FM.…”

Human Endogenous Retrovirus as Therapeutic Targets in Neurologic Disease

“…Beyond MS, temelimab seems to be effective in other HERV-W/MSRV-related diseases, such as CIDP or T1D. Therefore, it might be of interest to assess its efficacy in the treatment of additional diseases, such as fibromyalgia or chronic fatigue syndrome, where the upregulated expression of HERV-W has been recently reported [ 44 , 46 ].…”

Endogenous Retroviruses in Nervous System Disorders

“…For other nervous system diseases, only a few studies have analyzed possible associations with HERV. Elevated expression of HERV has been found in progressive supranuclear palsy [ 163 ], chronic inflammatory demyelinating polyradiculoneuropathies [ 165 ], fibromyalgia [ 166 ], myalgic encephalomyelitis [ 167 , 168 , 169 ], prion disease [ 170 , 171 , 172 ], and spinal and bulbar muscular atrophy (SBMA) [ 173 ]. In the case of SBMA, HERV RNA was found unchanged but elevated levels of processed gag antigens have been found.…”