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.

BackgroundRecent studies indicate that adipokines affect tissues and cells involved in rheumatoid arthritis (RA), including synovium, cartilage, bone, and immune cells.1, 2, 3 Nesfatin-1, a member of the adipokine family, was identified in 2006 as a potent anorexigenic peptide involved in the regulation of homeostatic feeding. Nesfatin-1 concentrations in serum and synovial fluid were closely correlated with disease occurrence and severity of knee osteoarthritis.4 We did not found any data about Nesfatin-1 levels in sera of rheumatoid arthritis (RA) patients.ObjectivesTo investigate the serum nesfatin-1 level in RA patients.MethodsAt baseline we measured Nesfatin-1 level in sera of 110 RA patients (mean age 54,07±11,32; hereinafter M±Std.dev.) and 60 healthy controls (52,09±14,12). The diagnosis of RA was set according to the ACR/.EULAR Classification Criteria for RA (2010) Serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured to assess inflammation severity. Nesfatin-1 in serum was determined by enzyme-linked immunosorbent assay (RaiBiotech, cat№ EIA-NESF).ResultsWe revealed that nesfatin-1 levels in RA patients was equal 50,49±34,05 ng/ml and was higher than of healthy controls – 31,61±3,17 ng/ml. We divided 120 RA patients into 2 subgroups – 1st (n=44) with normal nesfatin-1 concentration in sera, and 2nd (n=66) – with increased nesfatin-1 level. We noted that 2nd group’s patients had higher DAS28 activity index, functional joints disability, higher levels CRP and ESR.ConclusionsThe present study shows that RA patients have increased serum Nesfatin-1 levels which strongly correlated with systemic inflammation and functional impairment in RA. These data sustained the pathogenic role of Nesfatin-1 in RA progression.References[1] Sivordova U, Zavodovsky B, Polyakova U, et all. Adiponectin as a useful marker for diagnosis of osteoporosis in rheumatoid arthritis patients. Osteoporosis Int. 2016;27(S.1):135[2] Seewordova L, Polyakova U, Zavodovsky B, et al. Adiponectin determination in rheumatoid arthritis patients complicated by osteoporosis. EULAR2016;75(S.2):970–971.[3] Polyakova Y, Sivordova L, Akhverdyan Y, Kravtcov V, Zavodovsky B. New biomarker for diagnosis of osteoporosis in rheumatoid arthritis patients. Annals of the Rheumatic Diseases, 2017 -76, 2- 699.[4] Zhang Y, Shui X, Lian X, Wang G. Serum and synovial fluid nesfatin-1 concentration is associated with radiographic severity of knee osteoarthritis. Med Sci Monit. 2015;21:1078–1082.Disclosure of InterestNone declared

Background:Rheumatoid cachexia is an under-recognized pathological condition, which is characterized by a loss of muscle strength and can be presented as a low fat-free mass and normal or high BMI in patients with rheumatoid arthritis determined by dual-energy X-ray absorptiometry (DEXA) [1]. Though fetuin-A is one of a major noncollagen proteins in bone tissue it is of interest to clarify its association with rheumatoid cachexia.Objectives:To define the prevalence of rheumatoid cachexia in Caucasian patients with rheumatoid arthritis determined by DEXA method and to study the association of serum fetuin-A levels with body composition and rheumatoid cachexia in this group.Methods:110 Caucasian patients with rheumatoid arthritis undergone DEXA with «Total Body» program. All patients fulfilled the 2010 ACR/EULAR classification criteria for rheumatoid arthritis. The diagnosis of rheumatoid cachexia was based on Engvall I.L. criteria: fat-free mass index less than 10th percentile with fat mass index above 25th percentile [1]. We used values for these indexes from the study performed in 2008 by Coin A. et al. on Italian population due to a lack of standard values [2]. Fetuin-A in serum was determined by enzyme-linked immunosorbent assay. 72 patients have been taking glucocorticoids for more than 3 months in dose equivalent or higher than 5 mg of prednisolone daily. Statistical analysis was performed using a software package “Statistica 12.0”. Parametric data is presented as M±St.dev, and nonparametric as Me [Q1-Q3].Results:Rheumatoid cachexia was diagnosed in 25 patients (22,7%) with mean age of 52,2±8,14 years. The prevalence of cachexia was the same in groups of patients who took glucocorticoids (n=16, 22,2%) and who didn’t (n=9, 23,7%; p = 0,465). Median cumulative dose of oral glucocorticoids in patients with rheumatoid cachexia was higher but fell just short of statistical significance (8,0 [2,9-13,5] g vs 5,4 [0,2-11,6] g; Z=-1,42; p = 0,156). Median serum fetuin-A levels were only slightly significantly lower in patients with rheumatoid cachexia (757,7 [700,5-932,0] µg/ml vs 769,3 [660,3-843,4] µg/ml; Z=-1,35; p=0,175). Positive statistically significant correlations were observed between serum fetuin-A levels and bone mass in right (r=0,222, p = 0,027) and left (r=0,263, p = 0,008) lower limbs, trunk (r=0,268, p = 0,007), gynoid region (r=0,293, p = 0,003), both lower limbs (r=0,246, p = 0,014) and whole-body (r=0,235, p = 0,019).Conclusion:Rheumatoid cachexia was diagnosed in 22,7% of patients with rheumatoid arthritis. No association was observed between glucocorticoids intake and rheumatoid cachexia, despite the expected influence of them on muscle mass. We may suggest that occurrence and pathogenesis of this condition is complex and should be studied more precisely. It is well-known that patients with such condition have a higher risk for metabolic syndrome, arterial hypertension and mortality. We observed positive correlations between serum fetuin-A levels and bone mass in lower limbs, trunk, gynoid region and whole-body. Considering that fetuin-A is also associated with bone mineral density [3], it may be regarded as a marker of bone remodeling.References:[1]Engvall I.L., Elkan A.C., Tengstrand B., Cederholm T., Brismar K., Hafstrom I. Cachexia in rheumatoid arthritis is associated with inflammatory activity, physical disability, and low bioavailable insulin-like growth factor. Scand J Rheumatol. 2008; 37 (5): 321–328.[2]Coin A., Sergi G., Minicuci N., Giannini S., Barbiero E., Manzato E., Pedrazzoni M., Minisola S., Rossini M., Del Puente A., Zamboni M., Inelmen E.M., Enzi G. Fat-free mass and fat mass reference values by dual-energy X-ray absorptiometry (DEXA) in a 20-80 year-old Italian population. Clinical Nutrition. 2008; 27 (1): 87-94.[3]Sari, A., & Uslu, T. The relationship between fetuin-a and bone mineral density in postmenopausal osteoporosis. Turkish Journal of Rheumatology. 2013; 28 (3): 195-201.Disclosure of Interests:None declared

ObjectivesTo study relationship between serum levels of nicotinamide phosphoribosyltransferase and laboratory markers of inflammation in patients with rheumatoid arthritis (RA).MethodsWe determined nicotinamide phosphoribosyltransferase level in sera of 140 patients with RA (96 women and 44 men) by indirect enzyme-linked immunosorbent assay (RaiBiotech, cat No. EIA-VIS-1). The control group consisted of 20 women and 10 men aged 22 to 55 years without complaints of pain in the joints throughout life. The mean duration of disease was 5.94±0.37 years.ResultsWe divided all RA patients into 2 groups: one group (118 patients) with elevated levels of nicotinamide phosphoribosyltransferase serum (more than 3.9 ng/ml) and second group (22 patients) - with normal range.In each of the two groups, the levels of CRP and ESR were determined.Patients with elevated levels of Nampt had the following laboratory parameters (M±m): ESR – 37.83±1,57, CRP – 56.09±3,73 (rate - less than 5.0 mg/l). The second group had following data: ESR 22.46±0,56, CRP 21,65±1.38. Thus, patients with elevated levels of nicotinamide phosphoribosyltransferase had significantly higher concentrations of ESR and CRP (p<0,001).ConclusionsThere is the relationship between the level of nicotinamide phosphoribosyltransferase serum and laboratory markers of inflammation in RA (CRP and ESR). The data indirectly confirm the hypothesis that increased levels of nicotinamide phosphoribosyltransferase in RA patients is associated with disease activity.Disclosure of InterestNone declared

Background:Interest in highly specialized tissue cytokines contributed to the discovery of new biologically active molecules. Nesfatin-1 (NF) - discovered in 2006 as an anorexigenic factor. NF-1 is believed to be involved in the regulation of energy homeostasis by regulating appetite and water intake. The role of NF-1 in the pathogenesis of inflammatory diseases is poorly understood. Recently, studies have found a relationship between an increased level of NF-1 and inflammatory markers in various pathologies.Objectives:Study of the level of nesfatin-1 in the blood serum of healthy people, determination of the correlation between the level of NF-1 with the severity of clinical symptoms and classic markers of inflammation in patients with RA.Methods:120 persons were examined: 90 patients with RA and 30 healthy people. All patients underwent a complete clinical and laboratory examination. Plasma NF-1 levels were determined using commercial test systems (RaiBiotech, cat # EIA-NESF) according to the manufacturer’s instructions. Patients with various forms of RA were comparable in age to the group of healthy individuals. Statistical processing of clinical examination data was carried out using the “STATISTICA 10.0 for Windows” software package. Quantitative data were processed statistically using the parametric Student’s t-test, qualitative data using the non-parametric chi-square test. The significance of differences between groups was determined using analysis of variance. The results were considered statistically significant at p <0.05.Results:The average level of NF-1 in blood serum in healthy individuals was 31.79 ± 3.21 ng / ml (M ± σ). The level of normal NF-1 values in healthy individuals, defined as M ± 2σ, ranged from 25.3 to 37.83 ng / ml. There was no significant difference in the levels of circulating NF-1 and BMI in healthy individuals and patients with RA (p> 0.05). The inverse relationship of a lower level of NF-1 with an increase in BMI was not significant.Group 1 (66 patients with RA) with increased serum NF-1 levels (> 37.83 ng / ml), and group 2 (44 patients) with normal values (<37.83 ng / ml). A high level of NF-1 was characteristic for patients with high activity according to DAS28, RF seropositive, ACCP-positive, with extra-articular manifestations, who had been ill for 10 years or more. A reliable relationship between the level of NF-1 in the blood serum and laboratory parameters of RA activity - ESR, CRP, was shown, and secondary synovitis was more common. Our data show a direct correlation between the NF-1 level of the pro-inflammatory markers of RA.Conclusion:The positive correlation between the level of NF-1 and classical markers of inflammation, such as CRP and ESR, confirms the involvement of NF-1 in the pathophysiology of inflammation in RA. This is also evidenced by the correlation of a high level of NF-1 in the blood serum with a more severe clinical picture of RA. It is known that NF-1 can promote the release of pro-inflammatory cytokines such as interleukin-8 (IL-8), interleukin-6 (IL-6), and macrophage inflammatory protein-1a (MIP-1a) in the chondrocytes of RA patients.It is necessary to further study the role of NF-1 in the pathogenesis of systemic inflammatory reactions and the possibility of targeting pro-inflammatory cytokines, the possibility of regulating the level of NF-1 by drugs.References:[1]Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R. Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R., Polyakova Yu.V., Sivordova L.E., Yakovlev A.T., Zborovskaya I.A. Serum nesfatin -1 as a marker of systemic inflammation in rheumatoid arthritis. Klinicheskaya Laboratornaya Diagnostika (Russian Clinical Laboratory Diagnostics). 2019; 64 (1): 53-56 (in Russ.).Disclosure of Interests:None declared