Detection of potential markers of primary fibromyalgia syndrome in human saliva

Abstract

In the last few years, many attempts have been carried out for the research of specific biological biomarkers in fibromyalgia (FM) since, so far, no laboratory tests have been appropriately validated for the diagnosis and the prognostic stratification of the disease. In our study for the first time, we carried out a proteomic analysis of the whole saliva of FM patients in order to evaluate salivary biomarkers. Twenty-two FM patients with all fulfilling the American College of Rheumathology diagnostic criteria for FM and 26 sex-and age-matched healthy subjects were enrolled in the study. Proteomic analysis was performed by combining 2-DE and MALDI-TOF-MS. The most relevant observation which emerged from the data analysis was the exclusive and significant over-expression of transaldolase and phosphoglycerate mutase I. These findings were validated by Western blot analysis and the total optical density confirmed the significant up-regulation of transaldolase and phosphoglycerate mutase I in FM samples with respect to healthy subjects. It was noteworthy that seven further salivary proteins resulted differentially expressed, namely: calgranulin A, calgranulin C, cyclophilin A, profilin 1, Rho GDP-dissociation inhibitor 2, proteasome subunit-α-type-2 and haptoglobin-related protein precursor. These preliminary results demonstrated the utility of salivary proteomic analysis in the identification of salivary biomarkers in FM patients and in clarifying some of the pathogenetic aspects of the disease.

Saliva diagnostics – Current views and directions

“…There are three major methods of high-abundance protein removal 164 : enzyme-substrate absorption method used for alpha-amylase affinity removal, 165 immunodepletion method, and combinatorial peptide ligand library (CPLL). 166 Proteomic analysis of saliva is commonly used in the diagnostics of oral diseases as well as general health disorders such as oral candidiasis, 167 OSCC, 168 glossodynia, 169 head and neck squamous cell cancer, 170 Sjö gren's syndrome 171 HIV, 167 autism, 172 fibromyalgia, 173 breast cancer, 174 lung cancer, melanoma, 82 or pancreatic cancer. 26 …”

Beta-2 Microglobulin in Whole Unstimulated Saliva Can Effectively Distinguish Between Sjögren’s Syndrome and Non-Autoimmune Sicca Symptoms

“…However, proteomic analysis of saliva has been already performed in patients with fibromyalgia and sB2M was not reported to be differentially expressed. 20 Therefore, this difference in the proportion of patients with fibromyalgia probably did not influence our results. Previous studies with sB2M have used parotid saliva.…”

Biomarkers in fibromyalgia: a review

“…In the wake of the interesting results previously reported in rheumatic conditions, such as rheumatoid arthritis, Sjögren's syndrome, and systemic sclerosis, which are known to frequently overlap with FM syndrome, [50][51][52] an Italian research group also investigated the salivary profile of FM patients. 53 From the analysis of whole saliva from 22 FM patients, the most interesting result was the observation of a significant overexpression of transaldolase (sensitivity of 77.3% and specificity of 84.6%) and phosphoglycerate mutase 1 (PGM-1) in FM patients with respect to healthy controls. Transaldolase is an enzymatic protein involved in the oxidative phase of the pentose phosphate pathway.…”

“…53 These proteins have an important role in the immune response, in the cytoskeleton remodeling, and in the inflammatory process, but their role in FM still remains controversial.…”