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 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: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
Background: Rheumatoid arthritis (RA) is an autoimmune rheumatic disease. Activated B-and T-lymphocytes, mast cells, macrophages, tissue fibroblasts play a leading role in its pathogenesis. The development of autoimmune inflammation is impossible without the influence of a large number of pro-inflammatory cytokines such as IL 1α and β, TNF α, IL 6, IL 17, IL 22. Currently, other classes of biologically active molecules, such as adiponectin, visfatin, nesfatin, fetuin A, are being actively studied in RA [1,2,3,4]. Pre-B-cell colony enhancing factor 1 (PBEF1) stimulates synthesis of matrix metalloproteinases and chemokines, supporting synovial inflammation caused by leukocyte infiltration. A positive correlation between visfatin and C-reactive protein confirms its role as a mediator of inflammation. It is believed that increased concentrations of PBEF1 can stimulate systemic inflammation. Objectives: The study the relationship between serum PBEF1 level and disease activity in RA patients. Methods: We observed 140 patients with a reliable diagnosis of RA, of whom 96 were women and 44 were men. The control group consisted of 20 women and 10 men aged from 22 to 55 years without complaints of pain in the joints during life. PBEF1 concentration in blood serum were determined by indirect enzyme-linked immunosorbent assay using commercial test systems (RaiBiotech, cat№ EIA-VIS-1) according to the manufacturer's instructions. Results: The level of normal values of PBEF1 in healthy individuals with a BMI of 18.5 to 24.9 kg/m2 was 0.14-3.9 ng/ml, with a BMI of 25 to 29.9 kg/m 2 -0 -5.9 ng/ ml. Elevated serum PBEF1 level was detected in 84.29% of RA patients. The ones with elevated PBEF1 levels of significantly more likely to have a higher degree of activity index DAS28 (χ 2 =48,293; p<0,001,), high level of anti-cyclic citrullinated peptide (anti-CCP) (χ 2 =5,386; p=0,0203), higher levels of C-reactive protein (χ 2 =8,159; p=0,0043), erythrocyte sedimentation rate (p<0,001), extraarticular manifestations of the disease (χ 2 =7,354; p=0,0067). Conclusion: PBEF1 can be regarded as an important link in the pathogenesis of rheumatoid arthritis and for the potential molecule for biological therapeutic agents.
cytokines and chemokines including IL-12B (P=0.07), IL-6 (P=0.07), IL-10 (P=0.12), . Conclusion: This study illuminates the downstream effects of neutralizing TNFα not previously investigated. Adalimumab had a pronounced effect on downregulation of the inflammatory CXCL subfamily chemokines IL-8, CXCL5, CXCL9, and CXCL10. This helps explain findings of diminished inflammatory cell migration into joints seen in the first trials with TNFα inhibitors and could be an important mechanism of action of TNFα inhibitors.[2] Further characterization of downstream effects of the multiple DMARDs used for the treatment of immune mediated inflammatory arthritis will help guide treatment strategies for these patients.
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