BackgroundAccording to many studies systemic lupus erythematosus (SLE) is associated with an elevated risk of cardiovascular diseases due to early development of atherosclerosis. Several investigators have found that cytokines, C-reactive protein are increased both in patients with systemic inflammatory disease and with cardiovascular pathology. However the evidences of the autoimmune etiology of atherogenesis are discussed.ObjectivesThe aim of our study was to determine an association of antiphospholipid antibodies (aPL), inflammatory markers and cardiovascular risk factors in patients with systemic lupus erythematosus and atherosclerotic alterations of the vessel wall.MethodsThe study included 40 female patients with SLE (met the ACR diagnostic criteria 1997), mean age 33,5 (27,5; 44,5) years old, disease duration 8,0 (5,0; 14,5) years, disease activity SLEDAI-2K 7,0 (4,0; 11,5) points. The control group was formed by 28 healthy women of the same age.The levels of LA, IgG/IgM antibodies to cardiolipin (aCL), β2-glycoprotein-1 (aβ2-GP1), high sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor - α (TNF-α), were determined with ELISA, according to the instruction of the manufactures. The presence of traditional (age, smoking, arterial hypertension, obesity, hypercholesterolemia) and non-traditional (disease duration, disease activity, the dose of prednisone) risk factors was assessed in patients with SLE.The atherosclerotic alterations of the common carotid artery were revealed ultrasonographically according to standard procedures.ResultsThe asymptomatic atherosclerotic alterations of the vessel wall were found in 60,00% patients with SLE, 28,57% in the control group.The comparative analysis of aPL, inflammatory markers revealed an increase of aCL IgG, aβ2-GP1 IgG, LA, hs-CRP, IL-6, TNF-α levels in SLE patients with atherosclerosis as compared to the control subjects without it (p<0,0001, p=0,0007, p=0,002, p=0,011, p<0,0001, p=0,00007, respectively). The levels of aCL IgG/IgM, aβ2-GP1 IgG/IgM, LA, IL-6, TNF-α in patients with SLE without atherosclerosis were higher than in the control group, but the levels of inflammatory markers and antibodies under study were lower, than in SLE patients with atherosclerosis.An association between aCL IgG and TNF-α in patients with atherosclerosis was revealed during correlation analysis. We did not find any correlations between aPL and inflammatory markers in SLE patients without atherosclerosis.Selection by traditional and non-traditional risk factors in subjects with atherosclerotic alterations revealed positive correlation between aCL IgG and TNF-α in obesity (r=0,610, p=0,021), in arterial hypertension (r=0,509, p=0,044), in nonsmokers (r=0,587, p=0,013), in the disease duration less than 10 years (r=0,626, p=0,039).ConclusionsThus, we revealed an association between disease duration, disease activity, detected by the degree of increased proinflammatory cytokines (TNF-α) and by the presence of cardiovascular risk factors, which confirms polyet...

BackgroundIt is known that some factors of the fibrinolytic pathway, such as fibrinogen, D-dimer, have been associated with an increased risk of coronary events and stroke. Many publications demonstrated an increase of early development of atherosclerosis in patients with rheumatic diseases. The data have been focused on carotid arterial atherosclerotic alterations, such as intima-media thickness and plaque formation.ObjectivesThe aim of our study was to assess the procoagulation state and its assotiation with inflammation in female patients with rheumatoid arthritis (RA) and early atherosclerosis.MethodsThe study included 37 female patients with rheumatoid arthritis (ACR, 1987), mean age 45,0 (33,0; 51,0) years old, disease duration 9,0 (3,0; 14,0) years, disease activity (DAS28=5,37 (4,69; 5,86) points. Twenty-eight healthy women of the same age formed the control group.The levels of platelet cells (PLT), activated partial thromboplastin time (APTP), fibrinogen were determined with coagulation analyser, while D-Dimer, LA, IgG/IgM antibodies to cardiolipin (aCL), β2-glycoprotein-1 (aβ2-GP1), high sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), were determined with ELISA.The presence of carotid atherosclerotic alterations was revealed ultrasonographically according to standard procedures.ResultsThe patients with RA had significantly higher levels of fibrinogen, D-Dimer, LA, aCL IgG, aβ2-GP1 IgG/IgM, hs-CRP, IL-6 and TNF-α than in the control group (Table 1).The atherosclerotic alterations were found in 48,65% patients with RA, 28,57% in the control group.We reveled positive correlation between PLT and DAS28 (r=0,626, p=0,005), aCL IgM (r=0,513, p=0,029), D-Dimer and hs-CRP (r=0,747, p=0,003), DAS28 (r=0,819, p=0,0006) in RA patients with carotid atherosclerosis, that reflects association between prothrombotic and inflammatory markers.Table 1.The levels of prothrombotic and inflammatory markersInvestigated parametersRA (n=37)Control group (n=28)P (M-U)Me (25; 75‰)Me (25; 75‰)PLT, x109/l278,0 (221,0; 344,0)230,0 (205,0; 268,0)0,007*APTP, s29,0 (27,0; 31,8)27,6 (26,5; 32,2)0,368Fibrinogen, g/l4,10 (3,67; 5,10)3,10 (2,84; 3,78)0,0006*D-Dimer, ng/ml371,31 (95,99; 1163,08)50,82 (27,72; 88,80)0,00003*LA1,22 (1,13; 1,38)1,04 (0,81; 1,16)0,007*aCL IgG, U/ml36,60 (26,20; 49,75)13,51 (10,26; 15,39)<0,0001*aCL IgM, U/ml22,90 (16,54; 50,74)15,15; 7,89; 27,00)0,002*aβ2-GP1 IgG, U/ml4,29 (2,39; 9,40)3,96 (3,43; 5,33)0,781aβ2-GP1 IgM, U/ml2,70 (1,82; 4,43)1,88 (1,42; 2,25)0,007*hs-CRP, g/l11,41 (3,45; 18,00)1,15 (0,57; 1,90)<0,0001*IL-6, pg/ml11,48 (7,99; 31,14)0,66 (0,23; 0,84)<0,0001*TNF-α, pg/ml1,39 (0,41; 2,69)0,00 (0,00; 0,00)0,0002*ConclusionsWe demonstrated the presence of prothrombotic state in patients with RA, who had higher levels of inflammatory markers too. Thus, we suggest that inflammation can influence the prothrombotic state in patients with RA, induce endothelial dysfunction and, as a result, early development of atherosclerosis.Disclosure of InterestNone declared

Использование широкого спектра биомаркеров лежит в основе разработки персонализированного подхода к диагностике и лечению ревматоидного артрита (РА). Целью работы стало исследование уровней ферментативной активности сыворотки крови, провоспалительных цитокинов, ферритина при РА и установление их клинического значения. В исследование включено 128 пациентов с достоверным диагнозом РА согласно критериям EULAR/ACR 2010, а также 33 здоровых добровольца. Определены уровни ДНКзной и гиалуронидазной активности сыворотки крови, фактора некроза опухоли альфа (ФНО-α), интерлейкина-6 (ИЛ-6), интерлейкина 17А (ИЛ-17А), ферритина. Ферментативная активность сыворотки крови, уровни ИЛ-6, ИЛ-17А и ферритина у пациентов с РА были значимо выше, чем в контрольной группе (р<0,05). Уровень ФНО-α у пациентов с РА не превышал контрольных значений. Проведено сопоставление уровней ферментативной активности сыворотки, провоспалительных цитокинов и ферритина с клиническими, лабораторными и инструментальными характеристиками РА. В результате обнаружен ряд взаимосвязей, которые указывают на возможности использования изучаемых показателей в качестве биомаркеров при РА. Ключевые слова: ревматоидный артрит, ДНКазная активность сыворотки, гиалуронидазная активность сыворотки, цитокины, ферритин.

Background and objectivesAutoimmune diseases are characterised by tissue damage and loss of function due to an immune response that is directed against specific organs. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens.Pancreatic zymogen granule protein 2 Glycoprotein 2 (GP2) has been identified as a major autoantigenic target of the so-called pancreatic antibodies. Antibodies to GP2 have demonstrated diagnostic significance for Crohn’s disease. Anti-GP2 autoantibodies are detected in 25–30% of patients with CD and in 5–12% of patients with UC. There are certain relationships in pathgenesis and clinical course of inflammatory bowel diseases and spondyloarthropathies.The aim of our study is to investigate the prevalence of anti-GP2 in patients with SpA and evaluate the potential impact in relationships between gut inflammation and development the systemic autoimmune process.Materials and methodsWe studied 87 patients with SpA (64 patients with ankylosing spondylitis (AS), 23 – with psoriatic arthritis (PsA). As healthy controls 160 adult blood donors were included. All patients are fulfilled respective latest classification criteria.Levels of anti-GP2 antibodies (IgA and IgG classes) have been detected by ELISA, employing recombinant human GP2 (Medipan GmbH, Germany). Cut-off levels, determined by manufactures, are ≥20 U/ml.ResultsAnti-GP2 IgA were more prevalent in SpA (39/87, 44.82%) in controls (6/160, 3.75%) (p < 0.001). PsA patients did not reveal a significant prevalence prevalence of anti-GP2 IgA (13/23, 56.52%) in comparison with AS patients (26/64, 40.65%, p = 0.3).Anti-GP2 IgG were more prevalent in SpA (17/87, 19.54%) patients than in controls (4/160, 2.5%) (p < 0.001). PsA patients showed a significantly higher prevalence of anti-GP2 IgG (9/23, 37.5%) in comparison with AS patients (8/64, 12.5%, p = 0.019).ConclusionsAnti-GP2 antibodies, considering as a novel CD-specific markers, are found to be positive in about 44% of patients with SpA. Moreover, the highest prevalence anti-GP2 IgA was observed in PsA patients. These data may help to find new interrelationships between gut inflammation and the development of autoimmune diseases.

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