Biomarkers identification in fibromyalgia syndrome

Fibromyalgia Syndrome (FMS) is a chronic syndrome characterized by widespread pain. FMS is a collection of other symptoms and overlapping conditions contribute to complicate the diagnosis, the assessment and the treatment. Unknown etiology and none laboratory tests have been appropriately validated for the diagnosis of the disease. The comparison of protein patterns in body fluids of diseased and healthy subjects has the potential to identify new disease-specific biomarkers. Some purine nucleotide metabolism disorders such as myoadenylate deaminase (MAD) deficiency report symptoms similar to those seen in FMS. In consideration of what described above, we carried out a serum proteomic analysis of FMS patients with respect to control subjects searching potentially useful biomarkers for the disease. In addition, we evaluated serum purine metabolite concentrations in patients affected by FMS and the relationships between their levels and FMS clinical parameters. Twenty-two females affected by FMS (according to the American College of Rheumatology, 1990) and twenty-two healthy women were recruited as controls for analysis of purine metabolite. Sixteen females FMS and twelve controls were enrolled in the study for the analyses of the proteome. Proteomic analysis was performed by combining two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) and serum purine levels were quantified using reverse phase high performance liquid chromatographic (RP-HPLC). In our study, using the proteomic approach, we have identified differentially expressed proteins, such as Transthyretin (TTR), Alpha-1 Antitrypsin (A1AT) and Retinol Binding Protein 4 (RBP4). The serum 4 concentrations of these proteins were significantly higher in FMS patients compared with healthy controls. TTR and RBP4 are retinoid transporters, moreover retinoid dysfunction is related to oxidative stress as well as A1AT. These results support the hypothesis that oxidative stress could be implicated in the pathophysiology of FMS. Moreover, considerably higher serum concentration of inosine, hypoxanthine and xanthine levels (p<0.001) and lower serum adenosine (p<0.05) were detected in the FMS patients when compared to healthy controls. Our data show a negative correlation between adenosine and the Fibromyalgia Impact Questionnaire (FIQ). Our results suggest that purines, in particular adenosine and inosine, may be involved in pain transmission in fibromyalgia.