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
BackgroundFetuin-A is an acute-phase protein with contradictory effects. It is well known that fetuin-A low levels are associated with calcification and higher risk of cardiovascular diseases and its level is downregulated by pro-inflammatory cytokines.1 Nevertheles, it was shown, that fetuin-A induces synthesis of pro-inflammatory cytokines in adipocites and macrophages.2 ObjectivesTo investigate the level of fetuin-A in women with rheumatoid arthritis (RA).MethodsAt baseline we measured fetuin-A level, femoral neck, total hip and LI-LIV BMD by DXA in 110 women with RA (mean age 54,5±12,6; hereinafter M±Std.dev.) and 30 healthy controls. Serum CRP and ESR were measured to assess inflammation. DAS28 was calculated to determine RA activity. The diagnosis of osteoporosis was set according to the recommendations of world health organisation – T-score≤−2,5 for patients without glucocorticoid therapy in anamnesis, T-score≤−1,5 for patients treated with glucocorticoid for 3 months in anamnesis or with an osteoporotic fracture in anamnesis. Fetuin-A in serum was determined by enzyme-linked immunosorbent assay.ResultsMean concentration of fetuin-A in group with RA was 765,69±120,64 ug/ml, which was lower than of healthy controls – 812,95 ug/ml (p=0,0438). Secondary osteoporosis was revealed in 52 patients (47%) with RA with mean level of fetuin-A at 733,7±18,83 ug/ml vs. 794,36±12,83 ug/ml (p=0,0078) of 58 (53%) non-osteoporotic patients. Moderate negative correlations were observed between fetuin-A and DAS28 (r=-0,4334; p<0,001), fetuin-A and CRP (r=-0,3148; p<0,001), fetuin-A and ESR (p=-0,344; p<0,001). Mean concentrations of fetuin-A were significantly different between the subgroups with moderate (3,2≤DAS28<5,1) and high disease activity (5,1≤DAS28) of RA patients and healthy controls: 742,41±12,07 ug/ml vs. 812,95 ug/ml (p=0,0021) and 663,9±39,14 ug/ml vs. 812,95 ug/ml (p<0,001).ConclusionsOur study confirms that lower levels of fetuin-A are associated with higher activity of RA and with the loss of bone mineral density.References[1] Brylka L, et al. Calcif Tissue Int2012;93(4):355–364.[2] Stefan N, et al. Diabetes2008;57(10):2762–2767.Disclosure of InterestNone declared
Министерство науки и высшего образования Российской Федерации Федеральное государственное бюджетное научное учреждение «Научно-исследовательский институт клинической и экспериментальной ревматологии имени А.Б. Зборовского» Федеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации
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
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