Gross Cystic Disease Fluid Protein-15(GCDFP-15)/Prolactin-Inducible Protein (PIP) as Functional Salivary Biomarker for Primary Sjögren's Syndrome.

BACKGROUND: Gross cystic disease fluid protein-15(GCDFP-15)/prolactin-inducible protein (PIP) is a secretory acinar glycoprotein of 14 KDa which we have recently described as significantly lower in salivary samples of patients with primary Sjögren's syndrome (pSS) in comparison to healthy volunteers by proteomic analysis. AIMS OF THE STUDY: (1) to validate our previous data on the decrease of GCDFP-15/PIP protein in a larger number of subjects with pSS (2) to integrate the proteomic results with complementary immunoassays in order better clarify the pathophysiological relevance of GCDFP-15/PIP in pSS exocrinopathy (3) to assess both the glandular expression of the GCDFP-15/PIP and the levels of glandular GCDFP-15/PIP mRNA in the patients' minor salivary gland (MSG) biopsies in order to verify whether the observed reduction of GCDFP-15/PIP in saliva may be related to a decrease in the protein production. PATIENTS AND METHODS: A total of 123 salivary samples from patients affected by pSS, no-SS sicca syndrome and sex- age-matched healthy volunteers were analyzed by different proteomic techniques (SELDI-TOF-MS, 2DE, MALDI-TOF-MS). The expression of GCDFP-15/PIP was then validated by western blot analysis. Real Time PCR and immunohistochemistry for GCDFP-15/PIP in the minor salivary glands (MSG) biopsies were then carried out. RESULTS: By using complementary proteomic analysis we found that a putative peak of 16547 m/z was among the best independent biomarkers for pSS able to discriminate between patients and healthy controls with a sensitivity of 96 % and a specificity of 70%, with a global cross validated error of 29%. We identified the peak as the GCDFP-15/PIP protein and verified that the intensity of GCDFP-15/PIP was significantly lower in pSS patients when compared to both no-SS sicca subjects and healthy controls (p<0.0001). GCDFP-15/PIP expression also correlated with both the salivary flow rate (r=0.312, p=0.023) and MSG biopsies focus score (r=-0.377, p=0.04). Finally, immunohistochemistry confirmed that GCDFP-15/PIP staining was faint in mucus acini and Real Time PCR showed that GCDFP-15/PIP mRNA was significantly lower in pSS patients when compared to both no-SS sicca subjects and healthy controls (p=0.023) thus supporting the hypothesis that the observed reduction of GCDFP-15/PIP in pSS saliva may be related to a decrease in the protein production. CONCLUSION: In this study by different complementary-omic techniques we confirmed the potential role of GCDFP-15/PIP as a novel biomarker for pSS. This finding might also be functionally important as GCDFP-15/PIP has previously been shown to bind to Aquaporin 5 (AQP5), a salivary gland water channel, critical to saliva formation that is known to be downregulated in pSS. It is likely that exploring the GCDFP-15/PIP/AQP5 axis will help better understand the mechanism of salivary gland dysfunction in pSS.

Fibromyalgia and sexual problems.

The aim of this review was to describe the recent literature concerning sexual dysfunction in fibromyalgic patients. To this end, we used the common online databases PubMed, MEDLINE and EMBASE (up to June 2012) and searched for the key words fibromyalgia (FM) and sexual dysfunction. All the studies examined underlined that FM is strictly associated with sexual dysfunction in women. The major findings observed were related to a decreased sexual desire and arousal, decreased experience of orgasm, and in some studies an increase in genital pain. The psychological aspects, together with the stress related to the constant presence of chronic widespread pain, fatigue and sleep disturbances, are certainly a major factor that adversely affects the sexuality of the patient with FM. Moreover, the drugs most commonly used in these cases may interfere negatively on the sexuality and sexual function of these patients. Therefore, the therapeutic intervention should be targeted and the side effects should be weighed up against the positive effects. It is of the utmost importance to recognise the problem of sexuality and sexual dysfunction in a more complex form of its expression and undertake a multidisciplinary therapeutic intervention to improve the quality of FM patients' life.

Absence of xenotropic murine leukemia virus-related virus in Italian patients affected by chronic fatigue syndrome, fibromyalgia, or rheumatoid arthritis.

The xenotropic murine leukemia virus-related virus (XMRV) has been recently linked to chronic fatigue syndrome in a US cohort in whom the virus was demonstrated in 67% patients vs 3.7% healthy controls. Albeit this finding was not substantiated by subsequent reports and eventually considered a laboratory contamination, the matter is still the object of intense debate and scrutiny in various cohorts of patients. In this work we examined well-clinically characterized Italian patients affected by chronic fatigue syndrome, and also fibromyalgia and rheumatoid arthritis, two chronic illnesses of basically unknown etiology which show quite a few symptoms in common with chronic fatigue syndrome. Although we used recently updated procedures and controls, the XMRV was not found in 65 patients with chronic fatigue syndrome diagnosis, 55 with fibromyalgia, 25 with rheumatoid arthritis, nor in 25 healthy controls. These results add to the ever-growing number of surveys reporting the absence of XMRV in chronic fatigue syndrome patients and suggest that the virus is also absent in fibromyalgia and rheumatoid arthritis.

[MALDI-TOF and SELDI-TOF analysis: "tandem" techniques to identify potential biomarker in fibromyalgia]. / MALDI-TOF e SELDI-TOF: due tecniche "tandem" per l'individuazione di potenziali biomarker nella fibromialgia.

OBJECTIVE: Fibromyalgia (FM) is characterized by the presence of chronic widespread pain throughout the musculoskeletal system and diffuse tenderness. Unfortunately, no laboratory tests have been appropriately validated for FM and correlated with the subsets and activity. The aim of this study was to apply a proteomic technique in saliva of FM patients: the Surface Enhance Laser Desorption/Ionization Time-of-Flight (SELDI-TOF). METHODS: For this study, 57 FM patients and 35 HC patients were enrolled. The proteomic analysis of saliva was carried out using SELDI-TOF. The analysis was performed using different chip arrays with different characteristics of binding. The statistical analysis was performed using cluster analysis and the difference between two groups was underlined using Student's t-test. RESULTS: Spectra analysis highlighted the presence of several peaks differently expressed in FM patients compared with controls. The preliminary results obtained by SELDI-TOF analysis were compared with those obtained in our previous study performed on whole saliva of FM patients by using electrophoresis. The m/z of two peaks, increased in FM patients, seem to overlap well with the molecular weight of calgranulin A and C and Rho GDP-dissociation inhibitor 2, which we had found up-regulated in our previous study. CONCLUSION: These preliminary results showed the possibility of identifying potential salivary biomarker through salivary proteomic analysis with MALDI-TOF and SELDI-TOF in FM patients. The peaks observed allow us to focus on some of the particular pathogenic aspects of FM, the oxidative stress which contradistinguishes this condition, the involvement of proteins related to the cytoskeletal arrangements, and central sensibilization.

Fibromyalgia: a critical digest of the recent literature.

Fibromyalgia is a common syndrome characterised by widespread pain and a constellation of other symptoms and overlapping conditions that contribute to complicate the diagnosis, the assessment and the treatment. Furthermore, the etiological causes for the moment only consist of assumptions, and the underlying pathogenetic mechanisms still remain to be clarified. For the above-mentioned reasons, with the present review we sought to provide an overview of the literature on fibromyalgia from both the pre-clinical and clinical studies indexed in PubMed during the last year, classifying original articles and reviews into etiopathogenesis, assessment and therapy.

Spasmophilia comorbidity in fibromyalgia syndrome.

OBJECTIVES: To evaluate the role of spasmophilia (SP) in fibromyalgia syndrome (FM). METHODS: Three hundred and fourteen patients (280 F, 34 M) with a diagnosis of FM or FM and spasmophilia (FM+SP) were recruited. Clinical assessment of patients and controls included the Questionnaires FIQ, HAQ and the tender point (TP) count. Life-time or ongoing psychiatric aspects were evaluated by trained psychiatrists by means of the classic scales: Structured Clinical Interview (SCID) for DSM-IV. The following analysis were evaluated: cytokine (IL1, IL2, IL6, IL8, IL10), TNF-α, cortisol, GH, ACTH, IGF1, 5HT, intracellular Mg, plasma calcium p(Ca), PTH, (25(OH)D) and thyroid functionality. Some typical symptoms were investigated. RESULTS: Eighty-one patients resulted positive for spamophilia (FM+SP), while 233 resulted negative for spasmophilia (FM). The mean TP number resulted higher in the FM group (15.33±3.88) with respect to FM+SP (12.88±6.17, p=0.016), while FIQ and HAQ did not differ between the two studied groups. FM patients exhibited a higher frequency of psychiatric disorders with respect to FM+SP patients (72% FM vs. 49% FM+SP, p<0.01). In particular the frequency of depression was 65.5% FM vs. 35% FM+SP (p<0.01). CONCLUSIONS: The presence of spasmophilia seems to influence psychiatric comorbidity which was less prevalent in FM+SP patients. FM is indeed characterised by an abnormal sensory processing of pain that seems to result from a combination of interactions between neurotransmitters, stress, hormones and the nervous system; spasmophilia would seem to be more linked to a dysfunction at the neuromuscular level.