Maria Paola Guzzo

Pathophysiology of fibromyalgia: a comparison with the tension-type headache, a localized pain syndrome.

Fibromyalgia (FM) is thought to occur because of the combination of interactions among neurotransmitters, such as neuropeptide Y (NPY), stressors, hormones, cytokines, and both the immune and sympathetic nervous systems. The aim of this study was to evaluate serum concentrations of cytokines, antipolymer antibodies (APA), and NPY in 51 patients with FM, 25 with tension‐type headache (TTH), and 15 healthy controls. Serum concentrations of eight different cytokines, APA and NPY, were measured. Interleukin (IL)‐1RA, IL‐6, IL‐10, and tumor necrosis factor‐alpha were higher in serum of FM patients compared with TTH patients and a significant correlation between IL‐10 and Fibromyalgia Impact Questionnaire score was observed. There was a significant difference between FM and TTH versus controls in NPY levels, but not in APA levels. Cytokines and NPY take part in pain modulation and even if they are altered in FM they cannot be considered as measurable biomarkers of disease.

Pathophysiology of fibromyalgia: A comparison with the tension-type headache, a localized pain syndrome: Annals of the New York Academy of Sciences

Fibromyalgia (FM) is thought to occur because of the combination of interactions among neurotransmitters, such as neuropeptide Y (NPY), stressors, hormones, cytokines, and both the immune and sympathetic nervous systems. The aim of this study was to evaluate serum concentrations of cytokines, antipolymer antibodies (APA), and NPY in 51 patients with FM, 25 with tension‐type headache (TTH), and 15 healthy controls. Serum concentrations of eight different cytokines, APA and NPY, were measured. Interleukin (IL)‐1RA, IL‐6, IL‐10, and tumor necrosis factor‐alpha were higher in serum of FM patients compared with TTH patients and a significant correlation between IL‐10 and Fibromyalgia Impact Questionnaire score was observed. There was a significant difference between FM and TTH versus controls in NPY levels, but not in APA levels. Cytokines and NPY take part in pain modulation and even if they are altered in FM they cannot be considered as measurable biomarkers of disease.

Pain and systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by heterogeneous clinical manifestations involving virtually the entire body. The pain in SLE can have different causes. The SLE classification criteria include mainly the musculoskeletal manifestations of pain, which are commonly reported as initial symptoms of SLE, such as arthralgia, arthritis and/or myalgia. Chronic widespread pain, which is typical of fibromyalgia (FM), is frequently associated with SLE. The aim of this review is to describe widespread pain and fatigue in SLE, and the association of SLE and FM. Although secondary FM is not correlated with the disease activity, it may interfere with the daily activities of SLE patients. Therefore it is necessary to identify its symptoms and treat them promptly to improve the quality of life of patients. In conclusion, it is essential to identify the origin of pain in SLE in order to avoid dangerous over-treatment in patients with co-existing widespread pain and FM.

AB0112 Pathogenetic mechanisms in early rheumatoid arthritis: possible correlation between th17 and treg cells and gut microbiota structure: a pilot study

Background In Rheumatoid Arthritis (RA) pathogenesis T helper17 (Th17) and T regulatory cells (Treg) are largely represented.1 Recent studies highlighted the role of intestinal mucosa environment in modulation of T cells function. The composition of gut microbiota influences the Th17/Treg cells balance and the host immune response,2 so the exposure to deranged intestinal microbiota may be crucial in RA. Objectives The aim of the study was to compare Th17 and Treg cells and gut microbiota composition in patients with early RA (ERA) and in a control group (CG) at baseline and after treatment. Methods Currently, 10 ERA patients and 10 subjects belonging to the CG have been enrolled. All ERA patients were evaluated before (T0) and after 3 months (T1) of treatment with methotrexate (MTX) and glucocorticosteroids (GCS). Blood and faecal samples were collected. After PBMC isolation, staining with coniugated mAbs targeting specific surface and intracellular antigens (CD4 and CD25, IL-17 and FoxP3 respectively) have been used in order to distinguish Th17 and Treg cells. The composition of the faecal microbiota has been analysed by Next Generation Sequences on Illumina MiSeq platform, through 16S rDNA V3-V4 targeted sequencing. Results At T0, the percentage of Th17 cells was higher in patients than in the CG (p<0.0001) while Treg cells were higher in the CG (p=0.013). At T1, the total number of CD4 +and Th17 cells was decreased (p=0.007, p=0.027) while the frequency of Treg cells increased (p=0.028). A normalisation of Treg cells, with frequencies comparable to CG, was present after treatment. Regarding gut microbiota, at phylum level no difference between patients at T0 and the CG were present but we observed a tendency to decrease in the frequency of Actinobacteria after therapy. Furthermore, the relative abundance of Actinobacteria correlated positively with the circulating levels of Th17 (p=0,012, r=0,59) and with the Th17/Treg at T0 (p=0,010, r=0,6), while Nitrospirae correlated positively with Treg (p=0,028, r=0,68) at T1. A significant increase of the relative abundance in the Lachnospiraceae family in patients at T1 compared with T0 (p=0,042) and CG (p=0,043) were noticed. Conclusions Our results highlight the presence of an imbalance between Th17 and Treg cells in patients with ERA. In agreement with literature,3 MTX and GCS influence on Th17 decreasing and Treg cells increasing in patients with ERA, so we can hypothesise that part of the clinical response is own to the improvement in T cells balance. Previous data4 reported that Actinobacteria are strongly correlated with the production of IL-17 and a reduction of Nitrospirae has been associated to increased inflammatory responses and to gut permeability in mice.5 Lachnospiraceae family play an important role in the maintenance of intestinal homeostasis.6 The correlation between gut microbiota composition and Th17/Treg axis observed in our patients may suggest the involvement of some bacteria family in Th17/Treg cells balance in the lamina propria of RA patients treated with MTX, even in the early phases of the disease. References [1] Alunno, et al. 2015. [2] Omenetti, Pizarro. 2015. [3] Szalay, et al. 2013. [4] Chen, et al.2016. [5] Serino, et al. 2012. [6] Wu, et al. 2016. Disclosure of Interest None declared

AB0838 A Microrna Signature in Liquid Biopsies for The Diagnosis of fibromyalgia

Background Fibromyalgia (FM) is a syndrome characterized by chronic widespread pain that affects about 2–8% of the general population, especially female gender [1].The pathogenesis of FM is not completely understood and diagnosis is clinical.MicroRNAs, a class of small non-coding RNAs of ∼22–24 nucleotides, are involved in different post-transcriptional processes and have been identified as important biomarkers in many diseases [2]. Recently, it has been hypothesized that the modulation of protein expression, potentially mediated by miRNAs, is one of the main characteristic of the central and peripheral sensitization, which is a basic process to development and maintenance of chronic pain, as in FM [3]. Objectives The aim of this study was to analyze the expression of circulating miRNAs in liquid biopsies (i.e. serum and saliva) of a group of selected FM patients. Methods Consecutive adults FM patients, according to both ACR criteria [4,5], and healthy donors were enrolled. Patients complaining of pain VAS more than 6 (0–10), with positivity of at least 14 tender points at clinical examination and free from drugs at the time of evaluation, were included in the study.Patients and controls completed the following questionnaires: Fibromyalgia Impact Questionnaire, Fibromyalgia Assessment Status, Health Assessment Questionnaire, Zung Self-Rating Anxiety and Depression Scale. After obtaining informed consent, samples from patients and controls were collected.Circulating miRNAs were extracted using miRCURY RNA Isolation Kit-Biofluids (Exiqon) and profiled using the Serum/Plasma Focus microRNA PCR Panel (Exiqon) following the manufacturers instructions.Data were analyzed by SPSS software. Results The study population consisted of 14 female patients, without diagnosis of autoimmune diseases, psychiatric or neurological disorders and neuromuscular diseases, and 14 healthy controls matched for sex and age.The exploratory profiling of circulating miRNAs in serum revealed that six miRNAs (miR-23a-3p, miR-1, miR-133a, miR-346, miR-139–5p and miR-320b) were significantly (p<0.05) and differentially regulated in FM patients compared to controls, whereas some of these miRNAs were expressed but not significantly modulated in saliva.We found a significant negative correlation (r =-0.608; p<0.05) between miR-320b and the score of depression scale.ROC curves for each miRNAs displayed a AUC greater than ∼0.7 and the best generalized linear model that can be employed to discriminate FM patients from healthy controls was obtained by taking into account only 5 miRNAs: miR-23a-3p, miR-1, miR-133a, miR-346 and miR-320b (AUC=0.954, sensitivity=100%, specificity=83.3%). Conclusions Our preliminary work outlines the importance of using circulating miRNAs in liquid biopsies as a powerful diagnostic signature for the diagnosis of FM.Although the expression and the modulation of miRNAs seem to be site specific, we suggested a panel of serum miRNAs that can be used in the future as potential predictors of FM.A wider cohort of patients will be necessary to integrate the results that we obtained in this work and to suggest a more robust predictive model to exploit as an additional diagnostic tool for FM patients. References Talotta et al. Clin Exp Rheumatol 2015 Andersen et al. Neurobiol Dis 2014 Gold et al. Nat Med 2010 Wolfe et al. Arthritis Rheum 1990 Wolfe et al. Arthritis Care Res 2010 Disclosure of Interest None declared