Identification of a MicroRNA Signature for the Diagnosis of Fibromyalgia

Abstract

BackgroundDiagnosis of fibromyalgia (FM), a chronic musculoskeletal pain syndrome characterized by generalized body pain, hyperalgesia and other functional and emotional comorbidities, is a challenging process hindered by symptom heterogeneity and clinical overlap with other disorders. No objective diagnostic method exists at present. The aim of this study was to identify changes in miRNA expression profiles (miRNome) of these patients for the development of a quantitative diagnostic method of FM. In addition, knowledge of FM patient miRNomes should lead to a deeper understanding of the etiology and/or symptom severity of this complex disease.MethodsGenome-wide expression profiling of miRNAs was assessed in Peripheral Blood Mononuclear Cells (PBMCs) of FM patients (N=11) and population-age-matched controls (N=10) using human v16-miRbase 3D-Gene microarrays (Toray Industries, Japan). Selected miRNAs from the screen were further validated by RT-qPCR. Participating patients were long term sufferers (over 10 years) diagnosed by more than one specialist under 1990 American College of Rheumatology criteria.ResultsMicroarray analysis of FM patient PBMCs evidenced a marked downregulation of hsa-miR223-3p, hsa-miR451a, hsa-miR338-3p, hsa-miR143-3p, hsa-miR145-5p and hsa-miR-21-5p (4-fold or more). All but the mildest inhibited miRNA, hsa-miR-21-5p, were validated by RT-qPCR. Globally, 20% of the miRNAs analyzed (233/1212) showed downregulation of at least 2-fold in patients. This might indicate a general de-regulation of the miRNA synthetic pathway in FM. No significant correlations between miRNA inhibition and FM cardinal symptoms could be identified. However, the patient with the lowest score for mental fatigue coincided with the mildest inhibition in four of the five miRNAs associated with the FM-group.ConclusionsWe propose a signature of five strikingly downregulated miRNAs (hsa-miR223-3p, hsa-miR451a, hsa-miR338-3p, hsa-miR143-3p and hsa-miR145-5p) to be used as biomarkers of FM. Validation in larger study groups is required before the results can be transferred to the clinic.

Unraveling molecular determinants of manual therapy: an approach to integrative therapeutics for the treatment of fibromyalgia and CFS/ME

“…On another side, Tam Tam et al, showed that miR-143 expression levels were significantly reduced in DRGs ipsilateral to CFA injection or after nerve damage [84], coinciding with our findings that miR-143 is down regulated in PBMCs of patients of FM suffering of chronic fatigue [16]. This miR, however, has been reported to be upregulated in plasma of CFS/ME patients [19].…”

“…Other miRNAs linked to FM and CFS/ME, in particular miR-21 and miR-223, also associate to pain in animal models [16,88,93]. While both miRs are increased in spinal cord after spinal cord injury, the second also increases in the prefontal cortex of the brain in a model of carrageenan induced facial inflammatory pain.…”

“…Other types of compressive treatments, such as neuromuscular taping, which also increases lymphatic and vascular flow, strengthening weakened muscles, have identified a panel of miRNAs that show changes associated to the treatment in a multiple sclerosis (MS) patient [113], some of which have been shown to appear deregulated, both, in FM [16,93,114] and in CFS/ME patients [88].…”

“…Interestingly, some of these miRs associated to microgravity unloading appear to be deregulated in FM and CFS/ME patients [16,123,18], suggesting that compressive MT may provide a therapeutic effect by restoring miRNA levels.…”

Optimized Treatment of Heparinized Blood Fractions to Make Them Suitable for Analysis

“…The selection process of these two groups of participants has been previously described by our group. 23 The disease state of the participants, which may in principle seem irrelevant to this study, allowed us to appreciate that our treatments seem valid for samples with low C4a concentrations (below 1000 ng/mL) (FM patients) as well as for samples with higher C4a readings (above 3000 ng/mL) (Controls) (Fig. 5).…”