Fibromyalgia: a proteomic approach to study a double-face disease.

Fibromyalgia is a chronic non inflammatory musculoskeletal disorder characterized by a variety of symptoms related to pain. The first criterion for the diagnosis requires patient to report at least 3 months of widespread pain. The second is widespread pain in response to a tender point examination. Common unspecific symptoms include fatigue, nonrestorative sleep, morning stiffness, mood disorders, anxiety, depression, cognitive dysfunction (e.g., memory problems, concentration difficulties, diminished mental clarity), irritable bowel and bladder syndrome, sexual dysfunction and sicca symptoms. In the last few years many attempts have been carried out for the research of specific biomarkers in fibromyalgia, but, at present, there are no specific markers and the diagnosis is basically clinical. In the present work we used two complementary proteomic approaches to obtain the whole saliva protein map of fibromyalgia patients: two-dimensional electrophoresis in combination with mass spectrometry and Surface enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS). The aim of this study was the evaluation of the global changes of protein profiles which occur in the disease and the research for any eventual diagnostic or prognostic salivary biomarkers, which could be used routinely, in the future, for the management of fibromyalgia patients. 22 fibromyalgia patients and 26 healthy subjects were enrolled in the analysis with two-dimensional electrophoresis; while for SELDI-TOF-MS technique saliva samples were collected from 63 patients and 63 controls. With two-dimensional electrophoresis we found the significant over-expression of transaldolase and phosphoglycerate mutase I. These findings were validated by Western blot analysis and the total optical density confirmed their significant up-regulation in fibromyalgia samples with respect to healthy subjects. It was noteworthy that seven further salivary proteins resulted differentially expressed: calgranulin A, calgranulin C, cyclophilin A, profilin 1, Rho GDP-dissociation inhibitor 2, proteasome subunit-a-type-2 and haptoglobin-related protein precursor. With SELDI-TOF-MS technique we highlighted also the presence of a pattern of proteins potentially useful to discriminate fibromyalgia patients from healthy subjects. These results demonstrated the utility of proteomic analysis in the identification of salivary biomarkers in fibromyalgia patients.