The purpose of this study was to determine the level of nesfatin-1 (NF-1) in the blood serum of healthy volunteers and patients with rheumatoid arthritis (RA) to establish the threshold for normal values of this parameter and to reveal the relationship between the level of NF-1 and clinical manifestations of RA. We examined 170 people, of which 110 patients with RA and 60 donors who made up the comparison group. The mean level of serum nesfatin-1 in healthy subjects was 31.61 ± 3.17 ng/ml (M ± σ). The level of normal values of nesfatin-1 in healthy individuals, defined as M ± 2σ, was from 25.27 to 37.95 ng/ml. These studies showed the relationship between the concentration of NF-1 and the severity of clinical manifestations of RA. We found that a higher serum level of NF-1 was characteristic of patients with a more severe clinical course of the disease. The data obtained indicate that high level of NF-1 positively correlates with higher concentrations of C-reactive protein and ESR. This data indirectly proves the pro-inflammatory effect of NF-1 and confirms the hypothesis about the primary role of systemic inflammation in the pathogenesis of RA.

BackgroundRecent studies have been suggested that adipokines and myokines may be implicated in bone metabolism and pathogenesis of osteoporosis (OP).1 Previous studies have revealed inverse correlation between irisin levels and vertebral fragility fractures, but no significant correlation was found between irisin and bone mineral density (BMD) as well as with lean weight. There is no previously published data about irisin levels in rheumatoid arthritis (RA) patients.2–4 ObjectivesTo investigate serum irisin levels in patients with RA.MethodsWe studied 170 people: 110 RA patients (mean age 53.58±12.32; hereinafter M±SD) and 60 healthy controls. All patients with RA were examined using dual-energy X-ray absorptiometry using LUNAR DPX-Pro densitometer. Osteoporotic fractures were confirmed by X-ray examination and/or by anamnesis data. All patients were passed through extensive clinical and laboratory examination, including N-terminal propeptide of procollagen type I, C-telopeptide of type I collagen, 25(OH)-vitamin D concentration. Serum irisin levels were measured by ELISA (BioVender test system, Cat №RAG018R).ResultsThe mean concentration of irisin in RA group was 14.48±7.07 mg/ml, which was significantly lower than of healthy donors – 20.49±4.82 mg/ml (p<0,001). We subsequently divided all of RA patients into two groups: the first one (n=44) included patients with reduced serum irisin levels (below 10.85 mg/mL), and the second one (n=66) with normal irisin levels (above 10.85 mg/ml). The first group had significantly higher activity (DAS28), increased frequency of extra-articular manifestations, disease duration more than 5 years, class III of functional joints disability and lower levels of 25(OH)-vitamin D. We also observed higher incidence of pathological bone fractures in this group (p=0,047). There wasn’t any significant correlation between serum irisin level and BMD at any localization, lean, or fat weight. We did not reveal any difference of bone turnover markers (serum C-terminal telopeptide of type I collagen, serum N-terminal propeptide of type I procollagen (P1NP)) between these groups.ConclusionsWe have therefore revealed relationships between decreased serum irisin levels, 25(OH)-vitamin D concentration and higher incidence of pathological bone fractures in RA patients. We found no connexion between serum irisin levels and BMD at any site and body composition. We could consequently suppose, that irisin levels may reflect bone quality or increased fall risk.References[1] Palermo A, Strollo R, Maddaloni E, et al. Irisin is associated with osteoporotic fractures independently of bone mineral density, body composition or daily physical activity. Clin Endocrinol (Oxf)2015;82(4):615–9.[2] Boström P, Wu J, Jedrychowski MP, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature2012;481(7382):463–8.[3] Colaianni G, Cuscito C, Mongelli T, et al. Irisin enhances osteoblast differentiation in vitro. Int J Endocrinol2014;2014:902186.[4] Sivordova LE, Zavodo...

Objective: Analysis and generalization of data related to visfatin involvement in the pathogenesis of inflammation at various stages of rheumatoid arthritis. Data Synthesis: Visfatin is an adipocytokine which has also been identified in non-adipose tissues. It influences directly on the maturation of B cells, which are involved in autoantibody production and T cell activation. Visfatin can promote inflammation via regulation of pro-inflammatory cytokines including TNF, IL-1β and IL-6. The concentration of circulating visfatin in rheumatoid arthritis patients is higher compared to healthy individuals. Several studies suggest that visfatin level is associated with rheumatoid arthritis activity, and its elevation may precede clinical signs of the relapse. In murine collagen-induced arthritis, visfatin levels were also found to be elevated both in inflamed synovial cells and in joint vasculature. Visfatin blockers have been shown to confer fast and long-term attenuation of pathological processes; however, most of their effects are transient. Other factors responsible for hyperactivation of the immune system can participate in this process at a later stage. Treatment of rheumatoid arthritis with a combination of these blockers and inhibitors of other mediators of inflammation can potentially improve treatment outcomes compared to current therapeutic strategies. Recent advances in the treatment of experimental arthritis in mice as well as the application of emerging treatment strategies obtained from oncology for rheumatoid arthritis management could be a source of novel adipokine-mediated anti-rheumatic drugs. Conclusion: The ongoing surge of interest in anticytokine therapy makes further study of visfatin highly relevant as it may serve as a base for innovational RA treatment.

Background There is some data that osteoarthritis (OA) may be part of systemic lipid metabolism disorder. Some authors suppose that fat tissue may be origin of biologically active substances such as adiponectin, resistin, leptin and visfatin that may influence on chondrogenesis. Now there is a question about a level adipokines in degenerative diseases of joints. In this connection the researches related to studying of those markers in OA are relevant. Objectives The aim of the study was to improve diagnostic, to clarify OA pathogenesis by examining the levels of adiponectin, resistin, leptin and visfatin in OA sera. Methods We examined 80 patients with OA and 50 healthy donors (HD). Adipokines level were determined by indirect immunoenzyme method using a commercial test systems (Bio Vendor, cat № RD195023100 for adiponectin; Bio Vendor, cat № RD191016100 for resistin; DBC Inc cat № CAN-L-4260 for leptin and RaiBiotech, cat № EIA-VIS-1 for visfatin measuring). Results We revealed decrease of adiponectin levels in 28 (35%) OA patients (2 - in HD group (4%), chi-square=16,66, p<0,001), increase of resistin levels – in 31 (38,75%) (1 - in HD (2%), chi-square=22,39, p<0,001), leptin - in 26 (32,5%) (2 - in HD (4%), chi-square=14,79, p<0,001), and visfatin - in 23 (28,75%) OA patients (3 - in HD (6%), chi-square=9,95, p<0,001). These results indicate that lipid metabolism in OA may be disturbed. There was no significant difference in adipokines levels depending on the sex of OA patients. Resistin and leptin levels in patients with metabolic syndrome (mean BMI = 36,8 ± 3,3, corresponds to the degree of obesity II) were significantly higher than in those without metabolic syndrome. Low levels of adiponectin, high levels of resistin, leptin and visfatin were noted in patients with OA with reactive synovitis, radiographic stage III-IV, functional impairment of the joints III. We observed an inverse correlation between adiponectin level and CRP, ESR, and WOMAC index, Lequesne indeces for gonarthrosis and coxarthrosis, direct correlation between resistin, leptin, and visfatin levels and CRP, ESR and algofunctional indices. Follow weight reduction (5 kg in 3 months) resulted in significant decrease leptin and resistin levels, the severity of articular symptoms and manifestations of insulin resistance. Conclusions Thus adipokines may have important significance in pathogenesis of OA. We suppose adiponectin may be a protective factor in OA. Patients with increased levels of resistin, leptin and visfatin have more aggressive manifestations of OA. Osteoarthritis patients with low adiponectin level and a high level of resistin, leptin and visfatinhave more severe form of disease. Disclosure of Interest None Declared

Background There are now some data about role of adipose tissue in the pathogenesis of chronic inflammatory processes. Adipokines can influence on inflammation in rheumatoid arthritis (RA) and other rheumatic diseases. The literature contains some data on relieving of collagen-induced arthritis in mouse model with pharmacological visfatin inhibition injection. We suppose that visfatin is involved in the processes of degradation of cartilage and development of inflammation in joint disease by stimulating of interleukin-6 and 8, tumor necrosis factor, metalloproteinase-1 and 3 production. Objectives The aim of this study was to investigate clinical and pathogenic significance of visfatin determination in sera of RA patients. Methods We observed 170 people: 120 patients with diagnosed RA and 50 healthy controls (HC). Serum visfatin levels were measured by ELISA- test (RaiBiotech, cat No. EIA-VIS-1). Results We revealed that visfatin level in HC was 2,30+1,72 ng/ml, (mean and standard error accordingly), in RA patients - 6,27+0,59 ng/ml (p<0,001). We noted increased visfatin level in 46 RA patients (38,3%). We divided 120 RA patients into 2 subgroups – 1st (n=46) with high visfatin level in sera, and 2nd (n=74) - with normal visfatin concentration. We revealed that patients in 1st group had a higher level of activity index DAS28 (II-III degree of activity), high levels of autoantibodies to cyclic citrullinated peptide, higher levels of C-reactive protein and erythrocyte sedimentation rate. Conclusions The present study shows visfatin may have important significance in RA pathogenesis. RA patients with high visfatin level in sera have more aggressive form of disease. In this study serum visfatin strongly correlated with systemic inflammation markers and functional impairment in RA. Thus serum visfatin could be used as marker of RA activity and progression. We suppose visfatins inhibition may be used as a new pharmacological target in RA treatment. References Busso N., Karababa M., Nobile M. et al. Pharmacological inhibition of nicotinamide phosphoribosyltransferase/visfatin enzymatic activity identifies a new inflammatory pathway linked to NAD. PLoS ONE 2008; 3: e2267. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2011