Objective: Consolidation of current research findings as well as the most important concepts regarding neutrophil extracellular traps (NETs) in rheumatoid arthritis. Data sources: Relevant publications released from 2004 to 2018 were identified using PubMed, Web of Science, Scopus, and eLibrary databases. Primary search terms used were “neutrophil extracellular traps” or “NETs” in combination with “rheumatoid arthritis”. Data synthesis: NETs are distinctive structures promoting capture and non-phagocytic cleavage of foreign substances. NETs usually consist of thin chromatin fibers decorated with various molecules of granular, cytosolic, and cytoskeletal origin. NETosis could develop in two ways: either with neutrophil death or when the viability of the cell prolongs. ROS generation and pronounced protein citrullination are essential during the initial phase of NETs formation. NETosis is considered to have certain immunological consequences, including DAMPs-mediated signalling, proinflammatory cytokine secretion, and contact of extensively modified self and foreign epitopes with antigen presenting cells. There are several putative pathogenetic links between NETosis, citrullination, neoepitope formation, and production of anticitrulline autoantibodies that can strongly influence rheumatoid arthritis progression. NET-induced vascular injury in rheumatoid arthritis could arise both directly from NETs and indirectly through enhanced thrombosis and atherosclerosis. Conclusion. NETs are currently estimated as a possible influential factor of rheumatoid arthritis initiation and/or progression, especially in the context of vascular involvement. NETs can also serve as a source of novel antigenic biomarkers for the diagnosis of rheumatoid arthritis.

BackgroundRecent studies report various metabolic disturbances in systemic scleroderma (SSc) patients. Purine and pyrimidine metabolic pathways are closely interrelated, underlying the central processes of cellular life. Alterations of the enzymes that control these metabolic conversions can disturb proliferation and differentiation of lymphocytes, therefore contributing initiation and progression of the immunopathological phenomena.Objectivesto characterise enzymatic patterns of the major purine and pyrimidine metabolic pathways enzymes in blood plasma and lysed lymphocytes depending on the SSc activity.Methods51 SSc patients and 30 healthy controls were enrolled in the study. Mean age of patients (Mean ±SD) was 42,8±1,3 years, mean SSc duration was 7,9±0,7 years. The diagnosis was verified in accordance with the international standards (ACR/.EULAR 2013 Disease activity was assessed in accordance with the national classification.1 Adenosine deaminase (ADA; EC 3.5.4.4); adenosine kinase (AK; EC 2.7.1.20); guanylate kinase (GK; EC 2.7.4.8), dihydroorotate dehydrogenase (DODH; EC 1.3.1.14); IMP dehydrogenase (IMPDH; EC 1.1.1.205); purine nucleoside phosphorylase (PNP; EC 2.4.2.1); thymidine kinase (TK; EC 2.7.1.21); thymidine phosphorylase (TP; EC 2.4.2.4); uracil/thymidine dehydrogenase (UDH; EC 1.17.99.4); cytidine deaminase (CDA; EC 3.5.4.5) activities were measured in blood plasma and lysed lymphocytes.ResultsWe revealed substantial changes in enzymatic activities related to both purine and pyrimidine metabolism in SSc. The increased DODH (p<0,001), IMPDH (p<0,001), PNP (p<0,001), TK (p<0,001), TP (p<0,01), UDH (p<0,001) activities in plasma and AK (p<0,001), IMPDH (p<0,001), TK (p<0,001) activities in lysed lymphocytes; the decreased ADA (p<0,001), GK (p=0,02), PNP (p<0,001) activities in lysed lymphocytes were observed in SSc patients in comparison with healthy controls. Plasma AK, DODH, IMPDH, PNP, TK, UDH activities positively correlated with SSc activity, as well as lymphocytic AK, IMPDH, TK activities did. Negative correlations with SSc activity were revealed for plasma ADA, GK, TP, and also for lymphocytic ADA, GK, DODH, PNP, TP, UDH, CDA. Plasma and lymphocytic adenosine deaminase as well as adenosine kinase activities were the most informative for minimal SSc activity detection, being a promising candidate marker.ConclusionsThe changes in enzymatic activity of purine and pyrimidine metabolism participate in pathogenesis of SSc. The enzymatic patterns studied can be used as auxiliary markers of SSc activity. The correction of purine and pyrimidine metabolism changes can be considered as one of the promising ways of increasing the effectiveness of SSc treatment.Reference[1] Guseva NG. Systemic scleroderma. M: Medicine1993;268.Disclosure of InterestNone declared

BackgroundThe systemic scleroderma (SSc) is connective tissue disease of unknown cause. The key points in development of SSc are the increased number of high collagen-producing fibroblasts in the skin, endothelial dysfunction and immune activation. Recent studies report various metabolic disturbances in SSc patients. Purine and pyrimidine metabolic pathways are underlies the central processes of cellular life. The changes in activity of purine and pyrimidine metabolism enzymes in blood plasma and lysed lymphocytes depending on the SSc activity were described by us earlier [1]. At the same time, there are publications that confirm the relationship between changes in ADA activity in red blood cells and pronounced immune disorders [2].Objectivesto characterize enzymatic patterns of the major purine and pyrimidine metabolic pathways enzymes in lysed red blood cells depending on the SSc activity.Methods51 SSc patients and 30 healthy controls were enrolled in the study. The diagnosis was verified in accordance with the international standards (ACR/EULAR 2013). Disease activity was assessed in accordance with the national classification [3]. Adenosine deaminase (ADA; EC 3.5.4.4); adenosine kinase (AK; EC 2.7.1.20); guanylate kinase (GK; EC 2.7.4.8), dihydroorotate dehydrogenase (DODH; DC 1.3.1.14); IMP dehydrogenase (IMPDH; EC 1.1.1.205); purine nucleoside phosphorylase (PNP; EC 2.4.2.1); thymidine kinase (TK; EC 2.7.1.21); thymidine phosphorylase (TP; EC 2.4.2.4); uracil/thymidine dehydrogenase (UDH; EC 1.17.99.4); cytidine deaminase (CDA; EC 3.5.4.5) activities were measured in lysed red blood cells.ResultsMean age of patients (Mean± SD) was 42.8±1.3years, mean SSc duration was 7.9±0.7 years. We revealed substantial changes in enzymatic activities related to both purine and pyrimidine metabolism in lysed red blood cells of SSc patients. The increased ADA (p<0,001), AK (p<0,001), IMPDH (p<0,001), TK (p<0,001), UDH (p<0,001) activities and the decreased DODH (p<0,001), PNP (p<0,001) activities in lysed red blood cells were observed of SSc patients in comparison with healthy controls. AK, IMPDH, TK, UDH activities positively correlated with SSc activity. Negative correlations with SSc activity were revealed for ADA, CDA, DODG, GK, PNP, TP activities.ConclusionThe progression of SSc goes with the imbalance of the purine and pyrimidine enzymes in a regular manner. Activity of the autoimmune inflammation is the factor that underlies the enzymatic pattern of purine and pyrimidine metabolism.References[1] Mozgovaya E., Bedina S., Trofimenko A., Zborovskaya I. The association between activity of purine and pyrimidine metabolism enzymes and disease activity in systemic scleroderma patients. Annals of the Rheumatic Diseases2018;77(2):1280.[2] Cowan M.J., Brady R.O., Widder K.J. Elevated erythrocyte adenosine deaminase activity in patients with acquired immunodeficiency syndrome. Proc Natl Acad Sci U S A. 1986Feb;83(4):108.[3] Guseva N.G. Systemic scleroderma. M.: Medicine,1993.268 p.Disclosure of InterestsNone declared

Background:Cardiovascular disease in rheumatoid arthritis (RA) is more common than in general population. Particular attention should be paid to cardiac dysfunction, as their timely diagnosis strongly affects the general outcome.Objectives:To assess the prevalence of arrhythmias and conduction disorders in patients with seropositive RA without clinical manifestations of coronary artery disease, as well as to determine their relationship with activity and duration of RA.Methods:The research was carried out in agreement with the WMA Declaration of Helsinki principles. 48 patients with seropositive RA were included in the study. The exclusion criteria were: age over 60 years; obesity; congenital heart defects; coronary artery disease; peripheral atherosclerosis; thyroid disease; diabetes mellitus. All patients were assessed using general physical, laboratory and instrumental survey including CBC, blood chemistry panel, as well as ECG. RA diagnosis was verified using the 2010 ACR / EULAR classification criteria. Central tendencies were expressed as mean ±SD.Results:All the included persons were women. Their average age was 50.50 ± 7.22 years, and average duration of the disease was 8.13 ± 2.34 years. All patients had articular form (without systemic manifestations) of moderate and high activity. The patients were treated with basic and NSAIDs therapy; no glucocorticoids were applied at the time of the examination. Using 12-lead ECG arrhythmias and conduction disorders were revealed in 27 (56.25%) of RA patients. Sinus rhythm deviations had the highest (31.25%) prevalence for all arrhythmias, comprising sinus tachycardias (18.75%), sinus bradycardias (6.25%), and sinus arrhythmias (6.25%). Premature beats were registered in 12.5% cases, being supraventricular and ventricular ones in equal proportions. We have found left anterior bundle branch block in 6 (12.5%) of patients. Despite absence of any angina symptoms, 9 (18.75%) of patients had myocardial repolarization disturbances, either as ST depression deeper than 0.1 mV or as negative T wave appearance, which were quite similar to silent myocardial ischemia manifestations. All the patients with these two features had RA history of more than 10 years. There was no relationship between the prevalence of the manifestations and radiographic stage of RA.Conclusion:Arrhythmias and conduction disorders are quite frequent finding in seropositive RA (56.25% and 18.75%, respectively). Their incidence and severity do not coincide exactly with the radiographic progression in joints, while their prevalence generally increases with disease duration.These data highlight the importance of additional Holter ECG monitoring in RA for revelation and treatment of silent life-threatening cardiovascular complications.Disclosure of Interests:None declared

BackgroundSerum uric acid (UA) level is the most important risk factor for gout. At the same time many people with hyperuricemia do not suffer from gout, and UA level can return to normal during gout exacerbation.Objectivesto improve the diagnostics of the gout.Methods53 gout patients were the target group. The mixed control group was consisted of 150 rheumatoid arthritis patients, 95 osteoarthritis patients, 55 ankylosing spondylitis patients. The diseases were diagnosed in accordance with the international standards. Adenine deaminase, Adenosine deaminase (ADA), AMP-deaminase (AMPDA), Guanine deaminase, Guanosine deaminase, Guanosine phosphorylase, 5'-nucleotidase, Xanthin dehydrogenase (XDG), Xanthin Oxidase, Purine nucleoside phosphorylase activities were determined in blood serum with subsequent evaluation of sensitivity (Se), specificity (Sp), likelihood ratio of positive (LRP) and, likelihood ratio of negative (LRN) result, predictive value of positive and negative results.ResultsThe AMFDA and ADA activities were defined as a screening marker to diagnose of the gout from a joint syndrome another genesis. Threshold AMPDA activity 1,67 IU was characterized with the predictive value of negative results (without taking into account the prevalence) near 100%, Se 98%, Sp 62,45%.Cutoff value (CV) of ADA activity (9,57 IU) was characterized with LRN 0,104, Se 92,45%, Sp 72,65%, the sum (Se+Sp 165,10%), which was maximum not only for this test but for all the studied enzymes. The predictive value of negative results (without taking into account the prevalence) was 98,20%. The clinically significant CV of positive result for the ADA activity definition was identified also: LRP was 6,93 (Se 22,64%, Sp 96,73%) for the range of 12.58 IU and above. This fact allows the use of this test not only for the screening, but also, in some cases, for the verification of gout with significant pretest probability of this disease.Two CV were selected for the XDG activity: 7,49 μM/l×min (Se 47,17%, Sp 97,14%) and 8,39 μM /l×min (Se 39,62%, Sp 99,59%). The result of XDG activity determining in the range of 7.49 - 8.39 μM /l×min is an important argument in favor of the gout presence, but this may be useful for differential diagnosis only at high pretest probability of the gout.ConclusionsDetermination of the ADA activity was gave way to AMPDA activity determination at the gout screening and to XDG activity determination at gout verification. However, the ADA multifunctionality, evidenced clinically significant presence of the second CV (positive results) and a small proportion of the cases, which covered a “grey area” between CV (27.48%), provided the ability to use this marker as a backup in the absence of diagnostically relevant AMPDA and XDG activities.Disclosure of InterestNone declared