Fibromyalgia autoantibody driven changes in the skin
- Diarienummer
- UKR24-0009
- Projektledare
- Agashkov, Kirill
- Start- och slutdatum
- 241231-251231
- Beviljat belopp
- 1 000 000 kr
- Förvaltande organisation
- Karolinska Institutet
- Forskningsområde
- Livsvetenskaperna
Summary
Fibromyalgia (FM) is a chronic disorder affecting 6% of the global population. FM is a widespread chronic pain condition that is accompanied by cognitive and sleep issues. FM causes disturbance in most elements of the individual’s life, leading to difficulties in performing daily and work-related activities. There are no effective treatments or valid diagnostic biomarkers. Respectively, individuals with FM are mistreated properly in the healthcare system. While the causes of the pathology are unknown, findings show the alterations of central pain pathways. Emerging data suggest that the involvement of the peripheral mechanism leads to increased neuronal excitability. Moreover, a recent finding from Camilla Svensson's lab provides solid data that FM autoantibodies play a key role in this pathology. Autoimmune components in FM can be game changers in the field for developing efficient treatment strategies and further finding diagnostic biomarkers. This project will explore the links between FM autoantibodies, immune cells, and enhanced neuronal excitability. For this, IgG isolated from FM patients or healthy controls will be transferred to mice, immunohistochemical analysis of the skin, single-cell RNA sequencing of the skin, and behavioral assessment will used to address the specific aims: Aim 1. Examine FM autoantibody-driven changes in the immune cell landscape in the skin. Aim 2. Explore the functional role of FM IgG and immune cells in developing neuronal excitability.
Populärvetenskaplig beskrivning
Fibromyalgia (FM) is a chronic disorder affecting 6% of the population. Widespread musculoskeletal pain and fatigue are the most common symptoms. FM negatively impacts most elements of the individual’s life, leading to difficulties performing daily and work-related activities. The causes of FM remain unknown. There is evidence that the procession of pain signals to the brain is altered in FM. New data, however, suggest that FM has an autoimmune component. Those antibodies circulating in the blood also contribute to the pain problem by enhancing pain sensitivity. The project will focus on the skin changes driven by FM autoantibodies, such as the characterization of immune cell changes and skin innervation that can be linked to pain. For purposes, antibodies from FM patients or healthy controls will be transferred to mice, and methodologies allowing assessment of the corresponding changes in skin cell landscape and nerve profile will be used. This line of research will provide new insights into mechanisms underpinning FM symptoms and has the potential to pave a pathway to future mechanism-based therapeutics to treat FM.