Tag: fibromyalgia immune system

Fibromyalgia syndrome—am I an autoimmune condition?

Abstract:

Assessments of serum-autoantibodies in fibromyalgia syndrome (FMS) date back to the 1980s and have yielded inconsistent results. Based on a new passive transfer paradigm, since 2021 causative involvement of immunoglobulin G–mediated autoimmunity in severe FMS has been demonstrated in several studies, which have included UK, Swedish, and Canadian patients. These findings open the path to the development of novel diagnostic and immune-therapeutic approaches.

Autoantibody targets and downstream mechanisms and the molecular processes that translate infection-, toxicity-, or stress-triggers into the FMS immune response in genetically or otherwise vulnerable individuals require study. These results in FMS also suggest that other chronic pain conditions or nonpainful symptom-based disorders may similarly be caused by noninflammatory minimally destructive autoantibody-mediated autoimmunity, thus offering hope for large groups of patients.

Source: Goebel A. Fibromyalgia syndrome-am I an autoimmune condition? Pain Rep. 2025 Jul 2;10(4):e1270. doi: 10.1097/PR9.0000000000001270. PMID: 40612406; PMCID: PMC12226001. https://pmc.ncbi.nlm.nih.gov/articles/PMC12226001/ (Full text)

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

Abstract:

Fibromyalgia (FM) is a chronic disease characterized by widespread musculoskeletal pain of unknown etiology. The condition is commonly associated with other symptoms, including fatigue, sleep disturbances, cognitive impairment, and depression. For this reason, FM is also referred to as FM syndrome. The nature of the pain is defined as nociplastic according to the latest international classification and is characterized by altered nervous sensitization both centrally and peripherally. Psychosocial conditions have traditionally been considered critical in the genesis of FM. However, recent studies in animal models and humans have provided new evidence in favor of an inflammatory and/or autoimmune pathogenesis.

In support of this hypothesis are epidemiological data of an increased female prevalence, similar to that of autoimmune diseases, and the frequent association with immune-mediated inflammatory disorders. In addition, the observation of an increased incidence of this condition during long COVID revived the hypothesis of an infectious pathogenesis. This narrative review will, therefore, discuss the evidence supporting the immune-mediated pathogenesis of FM in light of the most current data available in the literature.

Source: Paroli M, Gioia C, Accapezzato D, Caccavale R. Inflammation, Autoimmunity, and Infection in Fibromyalgia: A Narrative Review. Int J Mol Sci. 2024 May 29;25(11):5922. doi: 10.3390/ijms25115922. PMID: 38892110; PMCID: PMC11172859. https://pmc.ncbi.nlm.nih.gov/articles/PMC11172859/ (Full text)

Is fibromyalgia an autoimmune disorder?

Highlights:

  • Certain aspects of FM are still controversial, including pathophysiology, which remain a subject of debate
  • FM shares many clinical features, sometimes designing overlapping diseases, with other conditions, including, chronic fatigue syndrome (CFS), sick building syndrome (SBS), post-COVID syndrome, and many others
  • Anti-GPCR (anti- G protein-coupled receptor antibodies), autoantibodies directed against the autonomic nervous system receptors, have been detected in the serum of patients with FM, and their titers correlated with clinical symptoms
  • Fibromyalgia belongs to nociplastic pain which means that the central nervous system is the driving force behind this pain mechanism, and the key phenotypic features include widespread pain, fatigue, and sleep, memory, and mood disturbances

Abstract:

Fibromyalgia (FM) is a multifactorial syndrome which includes not only widespread pain and stiffness, now recognized as major symptoms, but also numerous other somatic, emotional, and neuropsychic manifestation. The lack of specific validated biological and instrumental biomarkers has made FM a condition of unexplained medical significance, and its pathophysiology remains controversial and subject to debate. The current hypothesis regarding the pathogenesis of FM proposes that its development is influenced by various mechanism, including genetic predisposition, stressful life events, inflammatory processes, and cognitive-emotional factors. However, despite the extensive research conducted to date, the available data do not provide a clear understanding of the pathogenesis of FM.
In this article, we report the opposing viewpoints of two leading experts who debate the question of whether FM is an autoimmune disease, based on scientific data regarding this condition. Both perspectives are discussed and the latest evidence on the pathophysiology of FM is reported to provide a comprehensive understanding of this complex syndrome.
Source: Clauw D, Sarzi-Puttini P, Pellegrino G, Shoenfeld Y. Is fibromyalgia an autoimmune disorder? Autoimmun Rev. 2024 Jan;23(1):103424. doi: 10.1016/j.autrev.2023.103424. Epub 2023 Aug 25. PMID: 37634681. https://www.sciencedirect.com/science/article/pii/S1568997223001581 (Full text)

Manual Therapy Improves Fibromyalgia Symptoms by Downregulating SIK1

Abstract:

Fibromyalgia (FM), classified by ICD-11 with code MG30.0, is a chronic debilitating disease characterized by widespread pain, fatigue, cognitive impairment, sleep, and intestinal alterations, among others. FM affects a large proportion of the worldwide population, with increased prevalence among women. The lack of understanding of its etiology and pathophysiology hampers the development of effective treatments.

Our group had developed a manual therapy (MT) pressure-controlled custom manual protocol on FM showing hyperalgesia/allodynia, fatigue, and patient’s quality of life benefits in a cohort of 38 FM cases (NCT04174300). With the aim of understanding the therapeutic molecular mechanisms triggered by MT, this study interrogated Peripheral Blood Mononuclear Cell (PBMC) transcriptomes from FM participants in this clinical trial using whole RNA sequencing (RNAseq) and reverse transcription followed by quantitative Polymerase Chain Reaction (RT-qPCR) technologies.

The results show that the salt-induced kinase SIK1 gene was consistently downregulated by MT in FM, correlating with improvement of patient symptoms. In addition, this study compared the findings in a non-FM control cohort subjected to the same MT protocol, evidencing that those changes in SIK1 expression with MT only occurred in individuals with FM. This positions SIK1 as a potential biomarker to monitor response to MT and as a therapeutic target of FM, which will be further explored by continuation studies.

Source: Bonastre-Férez J, Giménez-Orenga K, Falaguera-Vera FJ, Garcia-Escudero M, Oltra E. Manual Therapy Improves Fibromyalgia Symptoms by Downregulating SIK1. Int J Mol Sci. 2024 Sep 1;25(17):9523. doi: 10.3390/ijms25179523. PMID: 39273470. https://www.mdpi.com/1422-0067/25/17/9523 (Full text)