Biomarkers in fibromyalgia: a review

Camillo Giacomelli,* Francesca Sernissi,* Alessandra Rossi, Stefano Bombardieri, Laura BazzichiRheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy *These authors contributed equally to the manuscript Abstract: Fibromyalgia is a common syndrome diagnosed by clinical criteria. The main symptom of fibromyalgia is pain, but patients frequently also complain about other nonspecific symptoms, such as headache, sleep disturbance, mood disorder, and cognitive impairment. In the light of the multifactorial origin of the disease and of the lack of objective diagnostic findings, several attempts have been made to find a reliable biomarker. For this reason, over the years, a number of patients and various biological samples have been studied, using many different approaches and techniques. Despite this, none of these studies has been able to find the proper biomarker. The aim of this review is to provide a critical overview of the current environment characterizing the search for fibromyalgia biomarkers. Keywords: genetics, proteomics, oxidative stress, fibromyalgi

Endothelial Progenitor Cells in Mixed Cryoglobulinemia

Objective.Endothelial progenitor cells (EPC) are a rare population of circulating cells involved in vascular homeostasis. Our aim was to analyze EPC in patients with mixed cryoglobulinemia (MC).Methods.EPC were evaluated by cytometry according to guidelines of the International Society for Hematotherapy and Graft Engineering in 17 patients with MC and 36 controls.Results.Numbers of EPC were significantly increased in MC compared to controls and correlated with cryocrit, but not with clinical manifestations of the disease.Conclusion.The high number of EPC might indicate an intact vascular repair ability. Alternatively, EPC might be defective in homing ability and their increase may represent the attempt to restore vascular integrity

A(2B )adenosine receptor activity is reduced in neutrophils from patients with systemic sclerosis

We conducted the present study to investigate protein expression and functioning of A(2A )and A(2B )adenosine receptors (ARs) in neutrophils of patients affected by systemic sclerosis (SSc). The presence of A(2A )and A(2B )ARs was assessed by immunoblotting using specific antibodies. Equilibrium A(2A )and A(2B )ARs binding parameters were evaluated by radioligand binding assay. Functional studies were conducted to investigate coupling of the A(2B )AR to the adenylyl cyclase pathway. This is the first report of the use of Western blot analysis to confirm the presence of A(2A )and A(2B )ARs in human neutrophils. No significant changes in A(2A )AR binding parameters or expression levels were detected between SSc patients and healthy control individuals. A significant decrease (65%) in the maximum density of A(2B )AR binding sites occurred in SSc neutrophils, whereas no changes in the affinity constant values were found. Moreover, a decrease in A(2B )AR mediated adenylyl cyclase activity was observed in patients with SSc. Our findings demonstrate the occurrence of selective alterations in A(2B )AR density and signalling in SSc

Adverse events during longterm low-dose glucocorticoid treatment of polymyalgia rheumatica: a retrospective study

To assess the occurrence of adverse events in a cohort of patients with polymyalgia rheumatica (PMR), treated with low-dose glucocorticoids (GC). METHODS: This was a retrospective study by review of medical records. RESULTS: We identified 222 patients who had a mean duration of followup of 60 ± 22 months and a mean duration of GC therapy of 46 ± 22 months. We found that 95 patients (43%) had at least 1 adverse event after a mean duration of GC therapy of 31 ± 22 months and a mean cumulative dose of 3.4 ± 2.4 g. In particular, 55 developed osteoporosis, 31 had fragility fractures; 27 developed arterial hypertension; 11 diabetes mellitus; 9 acute myocardial infarction; 3 stroke; and 2 peripheral arterial disease. Univariate analysis showed that the duration of GC treatment was significantly associated with osteoporosis (p < 0.0001), fragility fractures (p < 0.0001), arterial hypertension (p < 0.005), and acute myocardial infarction (p < 0.05). Cumulative GC dose was significantly associated with osteoporosis (p < 0.0001), fragility fractures (p < 0.0001), and arterial hypertension (p < 0.01). The adverse events occurred more frequently after 2 years of treatment. Multivariate analysis showed that GC duration was significantly associated with osteoporosis (adjusted OR 1.02, 95% CI 1.02-1.05) and arterial hypertension (adjusted OR 1.03, 95% CI 1.01-1.06); GC cumulative dose was significantly associated with fragility fractures (adjusted OR 1.4, 95% CI 1.03-1.8). CONCLUSION: Longterm, low-dose GC treatment of PMR is associated with serious adverse events such as osteoporosis, fractures, and arterial hypertension; these adverse events occur mostly after 2 years of treatment

Erratum to: MRI pattern of arthritis in systemic lupus erythematosus: a comparative study with rheumatoid arthritis and healthy subjects

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Salivary gland ultrasonography: a highly specific tool for the early diagnosis of primary Sjögren's syndrome

INTRODUCTION:Recently, a great interest has arisen for salivary gland ultrasonography (SGUS) as a valuable tool for the assessment of major salivary gland involvement in primary Sjögren's syndrome (pSS. The aims of this study were to test the accuracy of SGUS for the early detection of pSSand to compare the diagnostic performance of SGUS with minor salivary gland biopsy (MSGB) and unstimulated salivary flow (USFR) in this context. METHOD:Patients with suspected pSS and symptoms duration of ≤5 years were consecutively enrolled in this study. The diagnosis of pSS was made according to the AECG criteria. SGUS was performed by two radiologists blinded to the diagnosis and a previously reported ultrasound scoring system (De Vita et al. 1992, cut-off ≥ 1) was used to grade the echostructure alterations of the salivary glands. Statistical analysis was performed using SPSS v16. RESULTS: This study included 50 pSS patients and 57 controls with no-SS sicca symptoms. The mean(SD) age of the pSS group was lower than non-SS group (47(13) vs 53(12)yrs, p = 0.006). No further differences between the two groups were observed. Patients with pSS showed a significantly higher SGUS score in comparison with controls (mean(SD) = 2.1(1.8) vs 0.0(0.4), p = 0.000). The SGUS cut-off ≥ 1 showed a sensitivity (SE) of 66 %, a specificity (SP) of 98 %, a positive predictive value (PPV) of 97 % and a negative predictive value (NPV) of 73 % for pSS diagnosis. The SGUS score correlated also with patients' MSGB/FS and USFR. CONCLUSIONS: This study confirmed the good performance of SGUS for the early non-invasive diagnosis of pSS. Further research in larger international cohort of patients is mandatory in order to assess the role of SGUS in the diagnostic algorithm of pSS

antiproteinuric effect of chemokine c c motif ligand 2 inhibition in subjects with acute proliferative lupus nephritis

Background/Aims: To test the role of chemokine C-C motif ligand 2 (CCL2) in the pathogenesis of lupus nephritis (LN), we evaluated the effects of CCL2 inhibition by bindarit therap