Mucosa-Environment Interactions in the Pathogenesis of Rheumatoid Arthritis.

Mucosal surfaces play a central role in the pathogenesis of rheumatoid arthritis (RA). Several risk factors, such as cigarette smoking, environmental pollution, and periodontitis interact with the host at the mucosal level, triggering immune system activation. Moreover, the alteration of microbiota homeostasis is gaining increased attention for its involvement in the disease pathogenesis, modulating the immune cell response at a local and subsequently at a systemic level. Currently, the onset of the clinical manifest arthritis is thought to be the last step of a series of pathogenic events lasting years. The positivity for anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF), in absence of symptoms, characterizes a preclinical phase of RA-namely systemic autoimmune phase- which is at high risk for disease progression. Several immune abnormalities, such as local ACPA production, increased T cell polarization towards a pro-inflammatory phenotype, and innate immune cell activation can be documented in at-risk subjects. Many of these abnormalities are direct consequences of the interaction between the environment and the host, which takes place at the mucosal level. The purpose of this review is to describe the humoral and cellular immune abnormalities detected in subjects at risk of RA, highlighting their origin from the mucosa-environment interaction.

Pain modulation in patients with fibromyalgia undergoing acupuncture treatment is associated with fluctuations in serum neuropeptide Y levels.

OBJECTIVES: Neuropeptide Y (NPY) is a neurotransmitter released by sympathetic neurons, which is probably involved in pain modulation. Acupuncture is increasingly used as an alternative or complementary means of controlling pain in rheumatic diseases such as fibromyalgia (FM), a chronic widespread pain syndrome accompanied by allodynia and hyperalgesia. The aim of the present study was to assess the effects of an acupuncture cycle on serum NPY levels in patients with FM, and identify possible correlations between its serum levels and clinical and clinimetric parameters. METHODS: The study involved 30 FM patients who underwent clinical and clinimetric evaluations and blood sampling at baseline and at the end of the treatment, and 20 healthy subjects who underwent blood sampling. RESULTS: The baseline serum NPY levels of the patients were higher than those of the controls. They had significantly increased by the end of the treatment, when there was also a statistically significant reduction in pain, the number of tender points number, and the clinimetric scores. CONCLUSIONS: These findings confirm the analgesic properties of acupuncture as a complementary treatment in FM, and indicate that NPY could play a role in pain modulation.

Circulating microRNA Profiles as Liquid Biopsies for the Characterization and Diagnosis of Fibromyalgia Syndrome.

This work was aimed at investigating the circulating microRNA (miRNA) profiles in serum and saliva of patients affected by fibromyalgia syndrome (FM), correlating their expression values with clinical and clinimetric parameters and to suggest a mathematical model for the diagnosis of FM. A number of 14 FM patients and sex- and age-matched controls were enrolled in our study. The expression of a panel of 179 miRNAs was evaluated by qPCR. Statistical analyses were performed in order to obtain a mathematical linear model, which could be employed as a supporting tool in the diagnosis of FM. Bioinformatics analysis on miRNA targets were performed to obtain the relevant biological processes related to FM syndrome and to characterize in details the disease. Six miRNAs were found downregulated in FM patients compared to controls. Five of these miRNAs have been included in a linear predictive model that reached a very high sensitivity (100 %) and a high specificity (83.3 %). Moreover, miR-320b displayed a significant negative correlation (r = -0.608 and p = 0.036) with ZSDS score. Finally, several biological processes related to brain function/development and muscular functions were found potentially implicated in FM syndrome. Our study suggests that the study of circulating miRNA profiles coupled to statistical and bioinformatics analyses is a useful tool to better characterize the FM syndrome and to propose a preliminary model for its diagnosis.

Nonsteroidal anti-inflammatory drugs in-vitro and in-vivo treatment and Multidrug Resistance Protein 4 expression in human platelets.

Platelet Multidrug Resistance Protein 4 (MRP4)-overexpression has a role in reducing aspirin action in patients after by-pass surgery. Aspirin induces platelet MRP4 over-expression, through megakaryocytes genomic modulation. Aim of our work was to verify whether other non-steroidal antiinflammatory drugs (NSAIDs) enhance platelet MRP4 expression and evaluate platelet function in patients who overexpressed MRP4. We evaluated MRP4-mRNA in a human megakacaryoblastic cell line (DAMI), treated with both COX-2 inhibitor (celecoxib) and traditional NSAIDs (diclofenac and naproxen). Osteoarthritis patients, who reported to take NSAIDs twice a week for at least four continuous weeks and a control population, who didn't take any drugs during the previous month, were enrolled. We evaluated platelet MRP4 amount, by both mRNA levels and protein expression (Western-Blot) and ADP induced platelet aggregation. DAMI cells treated with celecoxib, diclofenac, and naproxen showed a significant increase in MRP4-mRNA expression compared to the mock culture. Osteoarthritis patient platelets presented a higher expression of MRP4 (both at mRNA and protein levels) and an increase in ADP-induced platelet aggregation compared to the control population. NSAID treatment induced platelet MRP4 overexpression. Osteoarthritis patients, who overexpress MRP4, showed platelet hyper-reactivity. These evidences could explain in part the increased cardiovascular risk present during NSAID treatment.

Fibromyalgia and nutrition: what news?

Fibromyalgia syndrome (FM) is a chronic, generalised pain condition usually accompanied by several associated symptoms, such as fatigue, sleep disturbance, headache, irritable bowel syndrome and mood disorders. Different medical treatments are used to treat fibromyalgia and the recent guidelines suggest that the optimal treatment consists in a multidisciplinary approach with a combination of pharmacological and non-pharmacological treatment modalities. Among non-pharmacological treatment, nutrition is a promising tool for FM patients. The aim of this review is to update the present knowledge about fibromyalgia and nutrition by means of a systematic search performed on Medline from January 2000 to December 2014. Nutritional deficiencies have been described in FM patients and the benefits of specific diet and nutritional supplementation are shown. Obesity and overweight, often present in FM patients, are related to the severity of FM worsening the quality of life in terms of higher pain, fatigue, worsened sleep quality and higher incidence of mood disorders. Weight control is thus an effective tool to improve the symptoms. Moreover, it seems reasonable to eliminate some foods from the diet of FM patients, for example excitotoxins. Non-coeliac gluten sensitivity is increasingly recognised as a frequent condition with similar manifestations which overlap with those of FM. The elimination of gluten from the diet of FM patients is recently becoming a potential dietary intervention for clinical improvement. In summary, this review reveals the potential benefit of specific dietary interventions as non-pharmacological tools as part of a multidisciplinary treatment for FM patients.

Complementary treatment in fibromyalgia: combination of somatic and abdominal acupuncture.

Fibromyalgia is a complex syndrome characterised by widespread pain associated with a variety of other signs and symptoms. The emerging consensus indicates that the best approach to treatment involves the combination of pharmacological and non-pharmacological interventions. Since acupuncture is a tool of traditional Chinese medicine increasingly used as an alternative or complementary therapy for the treatment of pain, the present study aimed to combine two different acupunctural methods (the somatic and abdominal one) in the treatment of 30 consecutive female FM patients and to evaluate the reduction of pain and the well-being state. The results showed a statistically significant reduction of the number of tender points and of pain. Moreover we observed a statistically significant reduction of FIQ, FAS, HAQ, disease activity VAS, ZSAS, ZSDS at the end of the treatment. In conclusion, these data suggest that the combination of two types of acupuncture could be a useful complementary treatment in FM patients, not only to control pain but also to improve associated symptoms and quality of life. As a result, acupuncture could be very useful to relieve pain in a multidisciplinary setting.

Fatigue and widespread pain in systemic lupus erythematosus and Sjögren's syndrome: symptoms of the inflammatory disease or associated fibromyalgia?

Fatigue and generalised pain are debilitating symptoms that negatively impact the quality of life in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). Chronic widespread musculoskeletal pain and fatigue are the clinical hallmarks of fibromyalgia (FM), a clinical entity which can be associated to connective tissue disease. The aim of the present study was to assess the prevalence of FM syndrome, fatigue and widespread pain in SLE and pSS patients and to evaluate the contribution of inflammatory disease and FM on those constitutional symptoms. Fifty SLE and 50 pSS patients were enrolled in the study. Patients rated fatigue, pain, and disease activity using a 100-mm visual analogue scale and completed the Health Assessment Questionnaire and the Fibromyalgia Impact Questionnaire. Zung depression and anxiety scales were used to quantify mood disorders. Tender points were evaluated using an algometer. Disease activity score as evaluated for each SLE and pSS patient. Fibromyalgia has been diagnosed in a significantly higher percentage of SLE patients than pSS patients (32% vs. 18%, p=0.022) even if the percentage of patients reporting fatigue and pain was higher among pSS patients. No correlation with disease activity was observed in either group of patients. FM seems to contribute to constitutional symptoms more in SLE than in pSS, suggesting a different underlying cause of fatigue and widespread pain in these two different connective tissue diseases.