Serum proteome profiles revealed dysregulated proteins and mechanisms associated with fibromyalgia syndrome in women

Abstract

Fibromyalgia syndrome (FM) is a multifactorial disorder whose pathogenesis and diagnosis are poorly understood. This study investigated differential serum proteome profiles in patients with FM and healthy pain-free controls and explored the association between serum proteome and clinical profiles in patients with FM. Twenty patients with FM (according to the American College of Rheumatology criteria, 2010) and 20 healthy pain-free controls were recruited for optimized quantitative serum proteomics analysis. The levels of pain, pressure pain threshold, sleep, anxiety, depression, and functional status were evaluated for patients with FM. We identified 22 proteins differentially expressed in FM when compared with healthy pain-free controls and propose a panel of methyltransferase-like 18 (METTL18), immunoglobulin lambda variable 3-25 (IGLV3-25), interleukin-1 receptor accessory protein (IL1RAP), and IGHV1OR21-1 for differentiating FM from controls by using a decision tree model (accuracy: 0.97). In addition, we noted several proteins involved in coagulation and inflammation pathways with distinct expression patterns in patients with FM. Novel proteins were also observed to be correlated with the levels of pain, depression, and dysautonomia in patients with FM. We suggest that upregulated inflammation can play a major role in the pathomechanism of FM. The differentially expressed proteins identified may serve as useful biomarkers for diagnosis and evaluation of FM in the future. Fibromyalgia syndrome (FM), manifesting as chronic widespread pain throughout the body, is associated with long-term pain and impaired quality of life, which can result in tremendous medical and socioeconomic burden 1-4. The prevalence of FM was reportedly between 0.2 and 6.6%, predominantly affecting women in the general population 5. The diagnosis of FM continues to be based mainly on clinical history taking and patients' complaints. Currently, no specific laboratory measure or specific biomarkers are available for the diagnosis of FM. FM has been recognized as a multifactorial disorder involving genetic, biological, and environmental factors. Although the pathogenesis of FM is poorly understood, altered central pain processing and pain sensitization are key elements in the pathogenesis of FM 2,6-8. Neuroimaging and neuroendocrine research have revealed that altered central nervous system structure and function occur in patients with FM 9-11. Patients with FM also exhibit a wide spectrum of associated symptoms such as sleep disturbance, depression, anxiety, fatigue, other pain disorders, and cognition problems 12. These symptoms add significant heterogeneity and difficulty in the clinical

Fibromyalgia: Pathogenesis, Mechanisms, Diagnosis and Treatment Options Update

“…Furthermore, serum proteome profiles revealed dysregulated proteins and pathways associated with fibromyalgia syndrome in women. Upregulated inflammation, as observed in the study of serum proteomics, plays a major role in the pathogenesis of FM [ 257 ]. Combining METTL18, IGLV3-25, IL1RAP and IGHV1OR21-1 levels can successfully distinguish FM patients from pain-free controls.…”

“…Combining METTL18, IGLV3-25, IL1RAP and IGHV1OR21-1 levels can successfully distinguish FM patients from pain-free controls. In the future, differentially expressed proteins could serve as potential biomarkers for FM diagnosis and clinical assessment [ 257 ].…”

ILRC : A Hybrid Biomarker Discovering Algorithm Based on Improved L1 Regularization and Clustering in Microarray Data

“…These methods will be introduced in detail in related work. Recently, these methods have been optimized to process proteomic/metabolic data acquired from massspectrometry in some diseases [16,17,18].…”

Efectos de un programa de telerrehabilitación basado en ejercicio terapéutico aeróbico en pacientes con fibromialgia durante la pandemia de la COVID-19

“…El sumatorio del UDP de los 18 puntos, medido mediante algometría, fue de 49,04 kg/cm 2 , con una desviación típica de 19,11 kg/cm 2 . Estos valores están por encima de los que muestran algunos estudios previos que utilizan los criterios diagnósticos de la ACR de 1990 como criterios de inclusión (Albers et al, 2018;Mannerkorpi et al, 2010), mientras que guardan similitud con estudios que utilizan criterios diagnósticos más recientes (Castro Sánchez et al, 2019;Han et al, 2020). Los criterios diagnósticos de la ACR de 1990 excluían a aquellos pacientes con menos de 11 puntos dolorosos a la presión de los 18 puntos corporales descritos.…”

“…Las variables clínicas registradas mostraron niveles moderados o severos de intensidad del dolor, así como hiperalgesia, impacto de la FM, fatiga, problemas de sueño, catastrofismo ante el dolor, kinesiofobia, alteraciones psicológicas, y baja capacidad funcional y fuerza de la muestra. Estos valores fueron similares a los mostrados por estudios previos en pacientes con FM (Albers et al, 2018;Castro Sánchez et al, 2019;Fioravanti et al, 2018;Giannotti et al, 2014;Han et al, 2020;Ide et al, 2008;Izquierdo-Alventosa et al, 2020;Lami et al, 2018;Lazaridou et al, 2019;Roelofs et al, 2007;Simister et al, 2018;Torres et al, 2015;Wolfe et al, 1996), con excepción del estado psicológico, la calidad de vida y algunas variables de capacidad funcional y fuerza, que mostraron mayor deterioro en este estudio.…”