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BackgroundSystemic lupus erythematosus (SLE) is a heterogeneous chronic autoimmune rheumatic disease with a wide range of clinical manifestations, characterized by impaired activation of cellular and humoral links of immunity, uncontrolled hyperproduction of autoantibodies of a wide spectrum to nuclear antigens and the formation of immune complexes that cause immuno-inflammatory damage to tissues and organs. This disease is characterized by periods of exacerbation and remission, over time, the activity of SLE may change, mainly in response to therapy. Despite this, patients can be classified according to the current or currently prevailing activity model.ObjectivesTo study the activity patterns of patients with SLE.MethodsThe retrospective-prospective study was conducted from 2019 to 2021 based on the study of the history of the disease and annual visits of patients with an assessment of the activity of SLE by SLE Disease Activity Index-2000 (SLEDAI-2K). Depending on the level of SLEDAI-2k flare index, the models of SLE activity, the number of exacerbations during the observation period and the period of the disease, as well as the predominance of organs and systems involved in the process were analyzed. The study included 183 patients with SLE (163 women and 20 men). The average age was 37.5±12.8 y.o. The duration of the disease was Me=9.9 [2.0; 16.0] years.ResultsThe clinical and immunological manifestations of SLE were evaluated in the study. The average number of exacerbations of SLE during the period of the disease was 2.9±1.9. The average number of exacerbations during the observation period was 1.1±0.78. The most frequent exacerbation was manifested by a lesion of the musculoskeletal system – 29,5% (54 patients), the skin-mucous system – 21,8% (40 patients) and lupus-nephritis – 21,8% (40 patients). The predominant activity model was relapsing-remitting disease (RRD) – 43,16% (79 patients), then chronic active disease (CAD) - 38,15% (70 patients), and minimal disease activity (MDA) – 7,1% (12 patients). Clinical quiescent disease (CQD) had 21 patients (11,47%). Models of SLE activity and involvement of systems and organs are presented in Table 1.Table 1.Models of SLE activity and involvement of systems and organs in patients with SLE.23 patients with involvement of the skin-mucosal system had 1 exacerbation of SLE in 3 years of the study. 23 patients with involvement of the musculoskeletal system had 1 exacerbation and 19 patients had 2 exacerbation of the disease in observation period. Exacerbation of lupus nephritis 1 time during the follow-up period was noted in 26 patients, 2 times - in 8 patients.ConclusionThe most frequent model of SLE activity is RRD, which characterizes periods of exacerbation and remission. The most frequent clinical manifestations of exacerbation of SLE are lesions of the skin-mucous and musculoskeletal systems, as well as lupus nephritis.ReferencesThe study was performed at the V.A.Nasonova Research Institute of Rheumatology within the framework of the fundamental topic FURS-2022-003.[1]Zen M, Bassi N, et. al. Disease activity patterns in a monocentric cohort of SLE patients: a seven-year follow-up study. Clin Exp Rheumatol. 2012 Nov-Dec;30(6):856-63. Epub 2012 Dec 17. PMID: 22765883.[2]Doria A, Gatto M, Zen M, Iaccarino L, Punzi L. Optimizing outcome in SLE: treating-to-target and definition of treatment goals. Autoimmun Rev. 2014 Jul;13(7):770-7. doi: 10.1016/j.autrev.2014.01.055. Epub 2014 Jan 27. PMID: 24480071.[3]Steiman AJ, Gladman DD, Ibañez D, Urowitz MB. Prolonged serologically active clinically quiescent systemic lupus erythematosus: frequency and outcome. J Rheumatol. 2010 Sep;37(9):1822-7. doi: 10.3899/jrheum.100007. Epub 2010 Jul 1. PMID: 20595281.Disclosure of InterestsNone declared

BackgroundThe study of other non-criteria antiphospholipid antibodies (aPL) may improve the stratification of patients with antiphospholipid syndrome (APS) and assist in the interpretation of conflicting results on aPL testing.ObjectivesTo determine the significance of antibodies to the phosphatidylserine/prothrombin complex (anti-PS/PT) in patients with systemic lupus erythematosus (SLE) and APS.MethodsThe study included 190 patients who signed informed consent, aged 37,0 [29,0-44,0] years and disease duration 7,0 [2,0-15,0] years. Male/female ratio was 44 (23)/146 (77). 123 (64,7%) of 190 patients had reliable SLE and 55 (29%) had PAPS. The control group was left with 100 relatively healthy, age-matched individuals. Classical aPL (IgG/IgM-aCL, IgG/IgM-αβ2-GP1, LA) were meassured at two time points separated by at least 12 weeks in all patients included in this study. IgG/IgM anti-PS/PT was determined by enzyme immunoassay (ELISA) using a Tecan sunrise absorbance microplate spectrophotometer (Austria) with an AESKULISA Serin-Prothrombin-GM antibody reagent kit. IgG/IgM anti-PS/PT were measured in U/ml. Values >18 U/ml were considered positive. The range of measurements was: 1 to 300 U/ml.ResultsIn 144 (76%) of 190 patients were revealed IgG anti-PS/PT, 55 (29%) - IgM anti-PS/PT, a combination of IgG anti-PS/PT and IgM anti-PS/PT was found in 53 (28%). IgG anti-PS/PT and IgM anti-PS were detected in 39 of the 70 (56%) remaining patients who were negative for criterion aPL. The median IgG anti-PS/PT was 101.2 U/ml [31,0-180,5] in patients with APS and was significantly higher than 23,7 [14,1-49,8] U/ml in patients without APS and controls. IgM anti-PS/PT levels in patients with and without APS were comparable. Thrombosis was significantly more common in patients with IgG anti-PS/PT: 95 (81,2%) of 117 patients with thrombosis compared with patients negative for IgG anti-PS/PT (22 (18,8%) of 46 patients) (χ2=4,85; P=0,03). Arterial, but not venous thrombosis, was associated with IgG anti-PS/PT positivity. IgG anti-PS/PT was detected in 53 (88,3%) of 60 patients with arterial thromboses, and in 7 (11,7%) of 46 patients of IgG anti-PS/PT negative. The incidence of thrombocytopenia in the SLE+APS patient group was associated with the presence of IgG anti-PS/PT, which was detected in 18 of 19 patients, versus 6 of 12 in SLE without aPL (PConclusionThe frequency of anti-PS/PT detection in the examined patients was high: 76% had IgG anti-PS/PT, 29% - IgM anti-PS/PT and 28% - a combination of them. The levels of IgG anti-PS/PT were significantly higher in patients with APS compared to patients without APS and controls. IgM anti-PS/PT values in patients with and without APS were comparable but higher compared to controls. Thrombosis was associated with IgG anti-PS/PT positivity. Arterial thrombosis was significantly more frequent in patients with IgG anti-PS/PT (χ2=4,85; P=0,006). The sensitivity of IgG anti-PS/PT for APS was 85%, and specificity was 64%; IgM anti-PS/PT had a lower sensitivity of 35%, but a higher specificity of 88%.The study was performed at the V.A. Nasonova Research Institute of Rheumatology within the framework of the fundamental topic FURS-2022-003.Disclosure of InterestsNone declared

BackgroundSystemic vasculitis (VS) is a severe autoimmune disease requiring active immunosuppressive therapy. The probability of infectious complications in these patients is very high. Immunization with the 23-valent polysaccharide pneumococcal vaccine (PPV-23) is required to reduce the risk of severe respiratory infections in this group of patients.ObjectivesThe aim of the study was to study the tolerability and safety of PPV-23 in patients with SV.MethodsAt this stage, the study included 13 patients with WS: 10 with vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA) (AAV), (5 with granulomatosis with polyangitis (GPA), 4 with eosinophilic granulomatosis with polyangiitis (EGPA), 2 - with microscopic polyangiitis (MPA)), 1 - with polyarteritis nodosa, 1 - with Takayasu’s arteritis (AT); of which 10 women, 3 men, aged 22 to 76 years. 9 (69%) patients were older than 50 years. Remission of the disease was observed in 1 patient (EGPA), in 3 - low disease activity, in 9 - active vasculitis (all 9 with AAV, BVAS from 4 to 13). All patients received glucocorticoids (GC): 2 - 55-60 mg/day, 9 - 10-20 mg/day, 2-2.5-5 mg/day; 5 -bDMARD: 4 - rituximab (RTM), 1 - TNF inhibitors; 11 - cytostatics (CS): 4 - mycophenolate mofetil (MM), 3 - azathioprine (AZ), 2 - cyclophosphamide (CPh), 2 - methotrexate (MTX). Two patients were on induction therapy (GC 55-60 mg + CPh) with a plan to switch to RTM. Only 1 patient with EGPA received HA as monotherapy. The 23-valent polysaccharide pneumococcal vaccine was administered subcutaneously in 0.5 ml (1 dose). The follow-up period was 1-6 months. During the visits, standard clinical and laboratory tests and the determination of antibodies to S.pneumoniae were carried out.ResultsVaccination tolerance was good in all patients. One (7,7%) patient with EGPA (in remission) had a mild local reaction (pain at the injection site) within 1 day. Another 1 (7,7%) patient with severe concomitant pathology (EGPA + multiple sclerosis) had a general reaction in the form of a transient increase in weakness in the lower extremities for up to 5 days (this symptom was a manifestation of polyneuropathy, persisted earlier, and to a greater extent was associated with multiple sclerosis than with EGPA). Vaccinal reactions were completely reversible and did not require additional prescriptions. During the follow-up period, no deterioration in the course of SV was recorded in any case, and no new autoimmune phenomena, both laboratory and clinical, were noted in any of them. 7 (53,8%) patients (all 5 with GPA, 2 with EGPA) had ENT lesions (destructive rhinosinusitis (5), sinusitis (2)) with frequent exacerbations. 1 patient with GPA reported a significant improvement in the condition of the ENT organs (no exacerbations of rhinosinusitis, disappearance of nasal discharge for 5 months). In the remaining 6 patients, the condition also remained stable, no progression of sinusitis was noted during the observation period (1-4 months). No infections of the lower respiratory tract were registered during the observation period.Conclusion1. All patients had a high risk of infectious complications: combined immunosuppressive therapy (92% of patients), age over 50 years (69% of patients), severe lesion of ENT organs (53,8% of patients). 2. The tolerance of PPV-23 vaccination was good. 3. There was no deterioration in the course of SV.Disclosure of InterestsNone declared

BackgroundSuicidal ideations in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) patients are associated with stress related depressive and anxiety disorders and can lead to higher mortality rates.ObjectivesTo describe the rates and potential causes of suicidal ideations in SLE and APS patients.Methods159 patients (62 with SLE, 49 with SLE and secondary APS, 48 with primary APS (PAPS)), mostly women (120 (75,5%)), were consecutively enrolled in the study. The mean (M±SD) age was 37,5±12,2 years. SLE activity was measured by SLEDAI. Suicidal ideations and mental disorders were detected by psychiatrist in semi-structured interview. The severity of mental disorders was measured with MADRS, HADS, PHQ9, PSS10, and quality of life with EQ-5D, LupusQoL.ResultsThe majority of patients had mental disorders (149 (93.7%)) with a predominance of anxiety and depressive spectrum (143 (89.9%)). Anxiety and depressive disorders in remission were diagnosed in 7 (4.40%) patients. Suicidal ideations in the past were revealed in 20 (12,6%) patients: in SLE - 9 (14,5%), SLE + APS - 8 (16,3%), PAPS - 3 (6,25%); suicidal attempt – in 1 (0,63%) patient with SLE + APS; autoaggressive behavior – in 11 (6,92%) patients (mainly presented as discontinuation of treatment in 10 (6,29%) patients): 6 (9,68%) - SLE, 4 (8,16%) - SLE + APS, 1 (2,08%) - PAPS. Current suicidal ideations were found in 16 (10,1%) patients: SLE - 5 (8,06%), SLE + APS - 5 (10,2%), PAPS - 6 (12,5%).The patients with suicidal ideations had higher depression (according to MADRS, HADS, PHQ-9) and anxiety (according to HADS) severity, they also presented with higher rates of stress perception (PSS-10) and poorer life quality (EQ-5D, LupusQol). The APS duration was significantly longer in patients with suicidal ideations; no differences in activity, severity and duration of SLE or steroid therapy were found, but SLE patients with current suicidal ideations compared to patients without them were 2 times more likely to receive rituximab (Table 1).Table 1.Description of patients with/without suicidal ideations.Characteristic, Me [25%; 75%] M±SDWith current suicidal ideations (n=16)Without current suicidal ideations (n=143)pn%n%SLE531,35740,2n/sSLE+APS531,34430,9n/sAPS637,44128,9n/sSLE duration, months156,0 [132,0; 216,0]84,0 [24,0; 68,0]n/sAPS duration, months228,0 [204,0; 348,0]120,0 [48,0; 180,0]0,001MADRS27,0 [14,5; 31,5]13,0 [8,0; 18,0]0,0001HAM-A18,5 [10,5; 25,5]15,0 [10,0; 21,0]n/sHADS:-depression7,0 [3,0; 9,0]3,0 [1,0; 6,0]0,009-anxiety9,0 [5,0; 14,0]6,0 [3,0; 9,0]0,04PHQ-912,0 [8,0; 15,0]6,0 [3,0; 12,0]0,02PSS-1032,7±8,7327,6±6,500,006EQ-5D0,56±0,290,72±0,220,009Lupus Qol113,7±24,9132,0±25,80,02Methylprednisolone intake:-Current dose, mg/day10,0 [0; 22,5]10,0 [5,0; 15,0]n/s-Сumulative dose, g16,9 [0,9; 61,2]7,2 [0; 28,9]n/sRituximab treatment531,22618,2n/sConclusionSuicidal ideations in SLE/ APS patients are mainly caused by anxiety-depressive spectrum disorders provoked by stress factors, no associations with the duration, activity and manifestations of the rheumatic diseases were found. Timely identification and therapy of depressive and anxiety spectrum disorders can prevent suicidal ideations and possible poor outcomes.Disclosure of InterestsNone declared

Backgroundclinical manifestations of Behcet’s Disease (BD) determine the prognosis and differ in patients of different ethnicity.Objectivesto describe the ethnicity related clinical features of Russian Federation’s cohort of BD patient’s.MethodsThis single center cohort study was carried out at the V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia from 1990 to 2021. 560 of BD patients (351 men (62,7%) and 209 (37,3%) women) were consecutively enrolled in the study. All the patients met the ICBD criteria (2014). The activity of the disease was determined using a Behcet’s Disease Current Activity Form (BDCAF). Clinical features of the BD were compared according to the patient’s ethnicities.ResultsThe majority of patients were natives of the North and South Caucasus (370 (66,0%)) and ethnic Russians (121 (21,6%)), 48 (8,57%) - natives of Central Asia, 12 (2,14%) – Ukrainians/ Moldovans, 6 (1,07%) – Yakuts/ Evenks and 3 (0,53%) - Jews. Mean age of Caucasus and Russians patients did not differ; the Russian were significantly older than Central Asia patients. Patients of different ethnicities did not differ in the BDCAF score. The most frequent clinical manifestations were oral aphthosis and skin involvements for all groups. Joints involvement occurred with a similar frequency in all groups. Genital ulcers were significantly more common in Russians and Caucasus compared to Central Asia patients. Ocular and vascular involvement was more typical for the Central Asia and the Caucasus natives. Gastrointestinal and neurological manifestations were more common for Russians. HLA-B51 positivity was less frequent in the Russians (Table 1).Table 1.BD manifestations in the Russian Federation depending on ethnicityCharacteristics,North and South Caucasus, n=370Russians, n=121Central Asia, n=48pМ±SD; n (%)123Mean age, yrs32,7±9,7434,5±11,029,9±9,15P2-3=0,012Mean age at disease onset, yrs22,5±9,7422,8±11,518,5±8,98p1-3=0,011p2-3=0,027BDCAF, point7,27±2,346,90±1,856,93±1,98n/sOral aphthosis360 (97,3%)117 (96,7%)46 (95,8%)n/sGenital ulcers263 (71,0%)88 (72,7%)26 (54,2%)Р1-3=0,015; Р2-3=0,017Skin involvement324 (87,6%)101 (83,5%)40 (83,3%)n/sPositive99 (26,7%)45 (37,2%)16 (33,3%)p1-2=0,020pathergy testOcular involvement232 (62,7%)58 (47,9%)34 (70,8%)p1-2=0,003, p2-3=0,005Gastrointestinal involvement59 (15,9%)33 (27,3%)7 (14,6%)p1-2=0,005Neurological involvement44 (11,9%)21 (17,3%)3 (6,3%)Р2-3=0,046Vascular involvement72 (19,5%)18 (14,8%)10 (20,8%)n/sJoints involvement246 (66,5%)83 (68,6%)27 (56,2%)n/sHLA-B5(51) positivity179 from 251 (71,3%)28 from 79 (35,4%)20 from 36 (55,5%)P1-2P1-3=0,044, P2-3=0,034ConclusionBehcet’s disease is most often detected in natives of the North and South Caucasus, Russians and natives of Central Asia in the Russian Federation’s cohort. Differences in the frequency of various clinical manifestations depending on the ethnicity of patients were revealed.Disclosure of InterestsNone declared

BackgroundPatients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have a two- to threefold greater risk of developing `thrombotic events. The expediency of thrombosis prevention in AAV continues to be discussed. The issue of prescribing anticoagulants (AC) is being discussedObjectivesRetrospectively to analyze the parameters of routine blood clotting indicators in patients with AAV depending on receiving AC.MethodsThe study included 45 patients with AAV (15 -with granulomatosis with polyangiitis (GPA), 15 - microscopic polyangiitis (MPA), and 15 - eosinophilic granulomatosis with polyangiitis (EGPA), aged 23 to 73 years. Duration of the disease was in 6 patients had 10 years. High AAV activity were registered in 22 patients (BVAS > 5)), 21 - low activity (BVAS < 5) points), 2 - remission (BVAS 0-1 points). The VDI damage index in 5 patients was 0, in 30 – from 1 to 3, in 10 – > 3 points. Glucocorticoids (GC) received 44: 78% of patients at a dose of 5-20 mg /day, 16% - >20-40 mg / day, 4% - >40-60 mg /day. AC 23 (51%) of 45 patients took AC. Blood clotting parameters were measured in 40 patients, including activated partial thromboplastin time (APTT), thrombin time (TT), soluble fibrin monomer complexes (SFMC), the number of platelets, 22 of them received AC.ResultsThrombosis in the past history was registered in 8 (18%) patients, 7 of them continued taking AС. 16 patients received AC without thrombosis for prevention ones. Patients with GPA received AK more often than patients with MPA and EGPA (73%, 40%, 40%, respectively).AC were prescribed in 51% of patients. AC were prescribed to 51% of patients receiving GC at a dose of up to 20 mg/day and 44% of patients with a dose of GC above 20 mg/day. The appointment of anticoagulants was associated with the duration of the disease. With a disease duration of up to 1 year, AK was prescribed in 33% of cases, with a duration of > 10 years - in 67% of cases. 59% of patients received AC with BVAS>5, 38% of patients - with BVAS5, while DOAC (87.5%) prevailed in patients with BVASConclusion1. Our retrospective analysis revealed that 51% of 45 patients with AAV received AC, they were more often prescribed with active AAV and more often with GPA.Our retrospective analysis showed that 51% of 45 patients with AAV received AС, more often with active AAV and more often with GPA.2. DOAC was prescribed more often (in 70% of cases) compared to others.3. The appointment of AC was associated with the duration of the disease.4. The dose of GC did not affect the decision to prescribe AС.5. Hemorrhagic complications during AС therapy were not observed in any case.Disclosure of InterestsNone declared

BackgroundPatients with systemic lupus erythematosus have an increased risk of detecting respiratory diseases.ObjectivesTo study the efficacy of 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE).MethodsThe study enrolled 72 patients diagnosed with SLE, including 64 women and 8 men aged 19 to 68 years with the disease duration ranging from 9 months to 42 years. Nine patients had high activity of disease, 17 - moderate, 40 - low, 6 - remission. Therapy: 68 patients received glucocorticoids (GC) 5-40 mg/day, 55-hydroxychloroquine (HC), 38 -cytostatics (CS), 26 - bDMARD: 14-rituximab (RTM), 10-belimumab (BLM), 2-RTM + BLM. Only 4 of 72 patients received monotherapy (GC-1, HC-1, CS-1, bDMARD-1); the remaining 68 received combined immunosuppressive therapy. PPV-23 in an amount of 0.5 ml (1 dose) was administered subcutaneously. Patients were observed and examined for 1 year after vaccination. Standard clinical and laboratory examinations were performed during the visits, and the serum antibody (AB) level to S. pneumoniae was determined. The presence of respiratory infections, including lower respiratory tract infections, during the year before and after vaccination was detected by questioning, as well as by studying medical records (hospital discharge papers, specialist reports, radiological and CT examinations). 25 patients were followed up for 5-6 years after vaccination.ResultsA year after vaccination, a more than twofold increase in the concentration of antibodies to pneumococcus persisted in 56% of patients. The clinical efficacy of the vaccine was superior to the resulting immunogenicity of PPV-23.Table 1.Respiratory infections in SLE patients at one year before and after vaccination (n=72)Respiratory infections1 year beforevaccination1 year aftervaccinationрLower respiratory infections31(43%)9(12,5%)0,0001Pneumonia, (including recurrent, 2-5 episodes)12(16,7%)5(7%)4(5,6%)-0,06Acute bronchitis13(18%)4(5,6%)0,04Exacerbation of chronic bronchitis6(8,3%)1(1,4%)0,1Upper respiratory infections14(19,4%)6(8,3%)0,04Acute sinusitis,11(15,3%)5(7%)0,1(Including recurrent)1(1,4%)-Exacerbation of chronic tonsillitis2(2,8%)-Acute otitis media1(1,4%)1(1,4%)During the year after vaccination, a decrease in episodes of infections of the lower respiratory tract by more than 3 times was recorded compared with the year preceding immunization (43% and 12.5%, respectively), p=0.0001. Not a single case of recurrent pneumonia was noted (before vaccination - in 5 patients). The number of infections of the upper respiratory tract has more than halved (19.4% and 8.3%, respectively). In 4 (5.6%) patients, non-severe pneumonia developed within a year after vaccination, all of these patients had risk factors for the development of respiratory infections: anti-B-cell therapy with the absence of an adequate vaccine response (3), interstitial lung damage (1), work activities and home environments associated with an increased risk of viral or bacterial infection (3). After a year of observation, 25 patients were followed up for another 4-5 years, the development of pneumonia was not registered in any case (2 out of 25 had pneumonia in the year prior to vaccination). At the same time, 5 years after vaccination, only 18% of patients had more than a 2-fold excess of the initial anti-pneumococcal antibodies.ConclusionSufficient immunogenicity and clear clinical efficacy of PPV-23 have been demonstrated in SLE patients receiving combined immunosuppressive therapy.Disclosure of InterestsNone declared

BackgroundThromboinflammation is a pathological process that is associated with uncontrolled inflammation, leading to hypercoagulability and thrombotic complications. Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are prototypical chronic thromboinflammatory diseases. Neutrophils are important cells in the development of systemic inflammation and thrombosis. Neutrophil reactivity (NEUT-RI), neutrophil granularity (NEUT-GI), immature granulocytes (IG), and neutrophil-to-lymphocyte ratio (NLR) are considered as inflammatory markers.ObjectivesTo determine the role of parameters of neutrophil activation (NEUT-RI, NEUT-GI), immature granulocytes (absolute (IG#), relative (IG%) counts), NLR, ESR in assessing inflammation in SLE, primary APS (PAPS), and SLE with APS.MethodsThe study included 80 patients and 40 healthy donors (HD). Patients were classified into three groups: Group 1 included 37 patients with SLE. The median age of patients with SLE was 34 years [28-43]. Group 2 included 20 patients with SLE+ APS (45 years [37-49]). Group 3 included 23 patients with PAPS (38 years [34,5-47,5]). Current disease activity was evaluated with SLEDAI-2K and adjusted GAPSS (aGAPSS).A complete blood count (WBC-white blood cell, NEUT#-absolute neutrophil count, NEUT-RI, NEUT-GI, IG%, IG count, NLR, thrombocytes, ESR-erythrocyte sedimentation rate) was performed with XN-1000 automated hematology analyzer (Sysmex, Japan).ResultsPatient characteristics are shown in Table 1. IG# and IG% levels were significantly increased in patients with SLE and SLE+APS compared to controls and PAPS. ESR levels was significantly higher in patients with SLE, SLE+APS, and PAPS compared to HD. There was no significant difference between NEUT-RI, NEUT-GI, NLR, fibrinogen and CRP levels in patients with SLE, SLE+APS, PAPS, and HD. The aGAPPS was positively correlated with the IG# (rs=0.46; р=0.028) and IG% levels (rs=0.49; р=0.017) in patients with PAPS. No correlation was found between the IG and SLEDAI 2K. The ESR was positively correlated with SLEDAI 2K in SLE patients (rs =0.54; р≤0.001).Table 1.Characteristics of patients with SLE, PAPS, SLE+APS, and healthy controls.ParametersM±SD, Me [25%; 75%], n (%)SLE (n=37)PAPS (n=23)SLE+APS (n=20)Healthy donors (n=40)pSLEDAI 2K7 [3.5-13]-4 [2-8]-р=0.03*Anti-dsDNA, IU/ml41.6 [13.6-101]-22.2 [10.7-69.9]-NSaCL IgG,n,%2 (5.4)16 (69.5)11 (55.0)-paCL IgM,n,%04 (19)1 (5)-P=0.034*aB2GP1 IgG,n,%2 (5.4)15 (65.2)11 (55.0)-paB2GP1 IgM,n,%1 (2.7)5 (21.7)1 (5)-P=0.053*LA positivity, n,%1 (2.7)15 (65.2)9 (45)-pTriple positive,n, %-14 (60.8)7 (35)-NSWBC, 109/l5.1 [3.8-7]5.6 [4.7-6.7]6.4 [4.9-7.7]6.2 [5.3-6.9]NSThrombocytes, 109/l231 [201-300]223.5 [189.5-270]226 [168-278]251 [210-290]NSNEUT#,109/l2.89 [1.84-3.71]3.6 [2.71-4.4]3.3 [3.1-5]3.55 [2.9-4.4]NSNEUT-RI, FI45.5 [43.8-47.3]44.2 [43.1-45.9]45.1 [43.5-47.3]44.0 [42.7-46.2]NSNEUT-GI, SI155.6 [151.6-158.0]154.85 [153.7-156.1]154 [151.2-157.8]153.7 [150.2-155.7]NSNLR1.8 [1.3-2.5]2.1 [1.4-3.1]2.3 [1.6-2,8]1.9 [1.5-2.4]NSESR, mm/h13 [7-20]14 [6.5-18]16 [13-19]7 [4-11]pIG#,109/l0.02 [0.01-0.07]0.01 [0.01-0.02]0.03 [0.02-0.05]0.01 [0.01-0.02],p=0.002*IG%0.4 [0.3-1.1]0.2 [0.2-0.4]0.4[0.3-0.7]0.2 [0.2-0.3]pCRP, mg/l2.2 [0.6-3.8]1.15 [1-1.4]2.5 [1.7-6.3]-NSFibrinogen, g/l.3.15 [2.8-3.6]3.35 [2.84-3.76]3.21 [2.9-3.8]-NS*a statistically significant test result (p < 0.05); NS-not significant;FI- fluorescence intensity; SI- scatter intensity; fl- femtoliter.ConclusionPatients with SLE and SLE+APS had significantly higher levels of immature granulocytes than controls and PAPS patients. In PAPS, immature granulocytes were positively correlated with aGAPSS values.The study was performed at V.A. Nasonova Research Institute of Rheumatology within the framework of the fundamental research FURS-2022-003.Disclosure of InterestsNone declared

BackgroundIn Behcet’s Disease (BD) some major organs are more involved in men and have worse outcomes. Gender related clinical features of BD are different in various countries.Objectivesto describe the gender related clinical features of Russian Federation’s cohort of BD patient’s.MethodsThis single center cohort study was carried out at the V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia from 1990 to 2021. 560 of BD patients (351 men (62,7%) and 209 (37,3%) women were consecutively enrolled in the study. All the patients met the ICBD (2014). The activity of the disease was determined using a Behcet’s Disease Current Activity Form (BDCAF). Clinical features of the BD were compared according to the patient’s gender.ResultsFemale to male ratio was 1,0: 1,7. The majority of patients were natives of the North and South Caucasus (66,0%) and ethnic Russians (21,6%). Mean (M±SD) age of male and female did not differed at the study inclusion (32,4±9,65 vs 33,8±10,5 years) and at disease onset (22,1±9,67 vs 22,6±10,8 years). The most frequent clinical manifestations were oral and genital aphthosis, skin, ocular and joints involvements. Men had higher BD-activity score (BDCAF) (pTable 1.BD manifestations in the Russian Federation depending on genderCharacteristics, М±SD; n (%)Male, n=351Female, n=209pMean age, yrs32,4±9,6533,8±10,5n/sMean age at disease onset, yrs22,1±9,6722,6±10,8n/sBDCAF, point7,43±2,236,62±2,11Oral aphthosis338 (96,3%)204 (97,6%)n/sGenital ulcers245 (69,8%)146 (69,8%)n/sOcular involvement240 (68,4%)102 (48,8%)Skin involvement320 (91,1%)166 (79,4%)Positive pathergy test117 (33,3%)48 (22,9%)0,005Gastro-intestinal involvement67 (19,1%)37 (17,7%)n/sNeurological involvement52 (14,8%)21 (10,0%)n/sVascular involvement75 (21,4%)24 (11,5%)0,002Joints involvement230 (65,5%)137 (65,6%)n/sHLA-B5(51) positivity158 from 243 (65,0%)71 from 175 (40,6%)ConclusionRussian Federation’s cohort of BD patients did not differ in clinical characteristics from other world regions. Ocular, skin, vascular lesions, positive pathergy test and HLA-B51 positivity are more frequent in men than in women.Disclosure of InterestsNone declared

BackgroundBehçet’s disease (BD) is a systemic variable vessel vasculitis with different clinical manifestations. BD does not have specific laboratory findings. Neutrophil hyperactivation is a major pathogenic factor in BD-related inflammation and tissue damage. Neutrophil reactivity (NEUT-RI), neutrophil granularity (NEUT-GI), immature granulocytes (IG), neutrophil-to-lymphocyte ratio (NLR), mean platelet volume (MPV), and platelet-lymphocyte ratio (PLR) are considered as inflammatory markers. Their role in BD remains unclear.Objectivesto determine the importance of parameters of neutrophil activation (NEUT-RI, NEUT-GI), immature granulocytes (absolute (IG#), relative (IG%) counts), NLR, MPV, PLR in assessing inflammation in BD.Methods29 patients with a reliable BD according to ICBD 2014 and 40 age-matched healthy donors (HD) without acute infectious diseases or cancer were included in the study (Table 1). Patients with BD were separated into two groups: 22 with active and 7 with inactive BD. Active BD was defined as involvement of at least two of the following features: oral ulcers, genital ulcers, uveitis, intestinal involvement, skin lesions, neurological involvement, arthritis, and vascular involvement. Current disease activity was evaluated with transformed Behçet’s Disease Current Activity Form (BDCAF). A complete blood count (WBC-white blood cell, NEUT#-an absolute neutrophil count, NEUT-RI, NEUT-GI, IG%, IG#, NLR, thrombocytes, MPV, PLR, ESR-erythrocyte sedimentation rate) was performed with XN-1000 automated hematology analyzer (Sysmex, Japan).Table 1.Comparative characteristics of patients with active/inactive BD and healthy controls.Parameters M±SD, Me [25%; 75%], n (%)Active BD (n=22)Inactive BD (n=7)Healthy donors (n=40)pGender: male/female, n16/64/316 /24NSVascular involvement,n73-NSBDCAF5 [5; 8]1 [0; 3]-pWBC, 109/l7.4 [5.9; 8.6]6.9 [6.5; 8.4]6.05 [5.2; 6.9]p=0.04*Thrombocytes, 109/l264.33±56.95305.11±104.82257.46±53.18NSNEUT#, 109/l3.91 [3.34; 5.03]3.89 [3.78; 5.5]3.41 [2.86; 4.13]NSNEUT-RI, FI45.95 [44.1; 47.1]46.25 [44.95; 47.75]43.7 [42.7; 46.2]р=0.049*NEUT-GI, SI154.84±4.05157.04±5.55153.37±4.7NSNLR1.64 [1.39; 1.91]1,9 [1.73; 2.6]1.83 [1.4; 2.28]NSESR, mm/6.5 [4.5; 17.0]12.0 [4.0; 15.0]7.0 [4.0; 11.0]NSIG#,109/l0.02 [0.01; 0.04]0.04 [0.01; 0.07]0.01 [0.01; 0.02]р=0.036*IG%0.3 [0.2; 0.4]0.45 [0.25; 0.65]0.2 [0.2; 0.3]р=0.018*CRP, mg/l2.5 [1.2; 7.4]2.45 [1.28; 4.65]-NSMPV, fl10.4 [9.7; 11.0]9.85 [9.6; 11.0]10.5 [10.1; 11.2]NSPLR116.45 [83.5; 138.6]151.55 [119.5; 171.1]137.1 [104.4; 160.1]NSFibrinogen, g/l3.48±0.82.88±0.4-NS*a statistically significant test result (p ≤ 0.05); NS-not significant;FI- fluorescence intensity; SI- scatter intensity; fl- femtoliter.ResultsA WBC count was significantly higher in BD patients compared to controls (Table 1). Patients with active BD had a higher WBC count than inactive. Patients with BD were found to have significantly higher levels of IG#, IG%, and NEUT-RI compared to HD. There was no significant difference between NEUT-GI, NLR, MPV, PLR, and ESR levels in patients with BD and HD. No significant difference in NEUT-RI, NEUT-GI, NLR, IG #, IG%, PLR, or MPV between active and inactive BD was found. These hematological parameters did not correlate with the transformed BDCAF score. IG# levels positively correlated with total leukocyte count (rs=0.656, ps=0.548, p=0.002). There was a tendency to a positive correlation between IG# and NEUT-GI (rs=0.354, p=0.050) and a negative correlation between IG# and PLR (rs=-0.356, p=0.052).ConclusionPatients with BD had significantly higher total WBC counts, immature granulocyte levels, and neutrophil reactivity than controls. Except for the leukocytes, there was no statistically significant difference in the studied parameters between patients with active and inactive BD.The study was performed at V.A. Nasonova Research Institute of Rheumatology within the framework of the fundamental research FURS-2022-003.Disclosure of InterestsNone declared

BackgroundThe role of antiphospholipid antibodies (aPL) not included in the International Classification Criteria for the verification of APS continues to be discussed.ObjectivesTo determine the clinical significance of IgG antibody for domain 1 β2-glycoprotein 1 (IgG-aβ2-GP1-D1) in patients with APS and SLE.MethodsThe study included 187 patients: 52 - with primary APS (PAPS), 12 - with probable APS (proAPS), 59 - with SLE+APS, and 64 - with SLE without APS. The comparison group included 49 patients with various rheumatic diseases (thrombosis without aPL (n=7), rheumatoid arthritis (RA) (n=10), Behcet’s disease (BD) (n=15), systemic sclerosis (SSD) (n=12), pregnant women (n=2), polymyositis (n=2) and Buerger’s endarteritis (n=1)) and a control group of 100 relatively healthy people. IgG/IgM-antibodies to cardiolipin (aCL) and IgG/IgM-aβ2-GP1 were determined by ELISA, and IgG-aβ2-GP1-D1 - by chemiluminescence assay (CMA) in all patients and controls.ResultsIgG-aβ2-GP1-D1 was detected in 37 (71%) of 52 patients with primary APS (PAPS), in 6 (50%) of 12 patients with probable APS (proAPS), in 42 (71%) of 59 patients with SLE+APS, in 17 (26%) of 64 patients with SLE, in 1 (2%) of comparison group and in none of control group. IgG-aβ2-GP1-D1 was significantly associated with PAPS and SLE+APS compared with patients with SLE (P=0,0002 and P=0,0001, respectively). IgG-aβ2-GP1-D1 levels were significantly higher in patients with PAPS, proAPS, SLE+APS, and SLE compared to control group (P < 0,000001, 0,03, < 0,000001, and 0,02, respectively). IgG-aβ2-GP1-D1 levels were significantly higher in patients with PAPS and SLE+APS compared to patients with SLE (P = 0,001 and P = 0,000005, respectively) and patients from the comparison group (P < 0,05). The frequence of IgG-aβ2-GP1-D1 positivity was associated with both thrombosis and obstetric pathology - the risk of developing clinical manifestations of APS was 9,69 and 4,19 times higher, respectively. A reliable correlation between antibodies to IgG-aβ2-GP1-D1 and arterial thrombosis can be traced. Obstetric pathology was detected in 32 of 37 women with a history of pregnancy and all were with IgG-aβ2-GP1-D1, versus 21 of 32 with negative IgG-aβ2-GP1-D1 (χ2=4,19; P=0,04). Eclampsia/preeclampsia and fetoplacental insufficiency in history was in 19 of 37 women with IgG-aβ2-GP1-D1, versus 7 of 32 with obstetric pathology but no IgG-aβ2-GP1-D1 (χ 2=6,35; P=0,01). The incidence of obstetric pathology was significantly associated with the presence of IgG-aβ2-GP1-D1 compared to women without these antibodies. Isolated IgG-aβ2-GP1-D1 positivity was reported in 13 (19%) of 70 aPL-negative patients. Obstetric pathology was present in all 6 (100%) women who had pregnancy in their disease course, and thrombosis in 7 (53%) of 13 patients. Sensitivity and specificity of IgG-aβ2-GP1-D1 depending on APS and its clinical manifestations are presented in the Table 1.Table 1.Sensitivity and specificity of IgG-aβ2-GP1-D1ThrombosisObstetric pathologyDiagnosis of APSSensitivity (%)635871Specificity (%)839287ConclusionThe frequency of IgG-aβ2-GP1-D1 positivity was higher in patients with APS compared to patients with SLE without aPL, comparison group and controls (P < 0,05). In 19% of cases, isolated IgG-aβ2-GP1-D1 positivity was observed. Positive IgG-aβ2-GP1-D1 levels were significantly associated with thrombotic complications and with obstetric pathology (χ2=8,84; P=0,002 and χ2=6,35; P=0,01). Specificity of IgG-aβ2-GP1-D1 for APS and its clinical manifestations (thrombosis and obstetric pathology) was higher than sensitivity.The study was performed at the V.A. Nasonova Research Institute of Rheumatology within the framework of the fundamental topic FURS-2022-003.Disclosure of InterestsNone declared

Background: According to the administrative data, confirmed by several meta-analyses, patients with rheumatoid arthritis (RA) in comparison with the General population shows an increased risk of venous thromboembolic complications more than twice. Drug prevention can reduce the risk of venous thromboembolism (VTE) in patients with rheumatic diseases. Objectives: The aim of this study was to analyze frequency of VTE, risk of bleeding and complications of the postoperative wound in patients with RA and osteoarthritis (OA) after total hip arthroplasty (THA). Methods: Study included 486 patients (212 - with RA and 274 - with OA) who underwent primary THA. Each group of patients was divided into 3 subgroups by type of drug therapy (1-nadroparin calcium; 2-dabigatran etexilate; 3-nadroparin calcium with transfer to dabigatran etexilate). Intra-and postoperative blood loss and the wound healing process were assessed during the first 7 days after surgery. Results: Postoperative VTE were reported in 36 (7.4%) of 486 patients. VTE in patients with RA were detected significantly less frequently than in OA (1.2% and 6.1%, p = 0.0013). Bleeding that required transfusion of blood in RA were found significantly more often than in OA (respectively 14.4% and 5.7% of cases; P Conclusion: The frequency of VTE, the risk of bleeding and complications of postoperative wound in patients with RA and OA after THA were analyzed. So, our study determined the dependence of VTE complications and bleeding risk according to the patient’s underlying nosology. Also the advantage of combined postoperative therapy over others was evaluated. Disclosure of Interests: None declared

Background Immunization with pneumococcal vaccines is an important factor of the prevention of severe respiratory infections in patients with rheumatic diseases (RD). Vaccination in systemic lupus erythematosus (SLE) is designed to ensure the continuity of immunosuppressive therapy, reducing the risk of severe exacerbations and death, and is effective from a pharmaco-economical standpoint. Objectives Investigation of the immunogenicity of 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with SLE, as well as the effect of immunosuppressive therapy on the vaccinal response. Methods 34 patients with a reliable diagnosis of SLE (30 women and 4 men aged 19 to 68 years) were included. The duration of the disease varied from 9 months to 20 years. At the time of vaccination, 3 patients had high, 4 – moderate, 22 – low disease activity, and 5 were in remission. Current therapy: 33 patients received glucocorticoids (GC) 5-30 mg/day in prednisolone equivalent, 27 – hydroxychloroquine, 17 – cytotoxic agents (CA) (7 – mycophenolate mofetil, 6 – methotrexate, 1 – mycophenolic acid, 3 – azathioprine,2 - cyclophosphamide),11 – biologics (BS): 5-rituximab (RTM), 6– belimumab (BLM). RTM was administered in doses of 500-1000 mg every 6-12 months, BLM – from 400 to 720 mg every month. 0.5 ml of PPV-23 (1 dose) was administered subcutaneously. During the visits standard clinical and laboratory tests were performed, as well as determination of antibody (AB) to S.pneumoniae serum level with VaccZymeTMPCPIg 2 sets (TheBindingSiteLtd, Birmingham, UK). Results 1 and 3 months after vaccination, most patients (82,4% and 96,7% respectively) had a significant (more than 2 times compared to baseline) increase of the concentration of AB to the S. pneumoniae cell wall polysaccharides. A year after the vaccination, 22 (64.7%) patients (responders) had a significant increase of the concentration of anti-pneumococcal AB. 12 (35,3%) patients were considered as non-responders, they did not have a significant increase of the AB level (table). p a–b=0,000002; p a–c=0,00009; p a–d=0,0002. Among 11 patients receiving BS, a complete vaccinal response was observed much less frequently than in patients without these drugs, 36.4% and 78.3%, respectively, p=0.04. In the group treated with RTM, the number of non-responders was greater than among patients receiving BLM (80% and 50%, respectively), but this difference is not significant, p=0.6. The addition of CA to the treatment regimen did not have an additional negative effect on the vaccinal response. Conclusion Sufficient immunogenicity of PPV-23 was shown in patients with SLE, including those receiving combined immunosuppressive therapy. At the same time, the use of anti-B-cell drugs in combination therapy resulted in a significant decrease of the vaccinal response Disclosure of Interests None declared

Background:The study of antiphospholipid antibodies (aPL), not included in the Sydney diagnostic criteria, in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) is poorly understood.Objectives:To determine the frequency of detection of IgA-aCL and IgA-aβ2GP1 and IgG antibodies to β2GP1 domain 1 (IgG-aβ2GP1-D1) in patients with APS with and without SLE.Methods:ELISA and chemiluminescence assays (CMA) were used to test 63 sera of patients: 22 (35%) with primary APS (pAPS) and 41 (65%) patients with APS and with SLE (secondary APS (sAPS)), with mean age 38,0 [33,0 – 43,0] years and disease duration 4,0 [0,1 – 9,9]. Both methods were used to test of IgG/IgM-aCL and IgG/IgM-aβ2GP1. CMA was used for research IgG/IgM/IgA-aCL, IgG/IgM/IgA-aβ2GPI and IgG-aβ2GP1-D1. Of them 49 (78%) (18 – with pAPS; 31 – with sAPS) displayed major thrombotic events and 18 of 22 pregnant women had pregnancy morbidity in past history. Lupus anticoagulant (LA) positivity was in 9 out of 12 patients who had it determined. LA was not investigated due to anticoagulant therapy in the remaining 52 patients.Results:IgG/IgM-aCL and IgG/IgM-aß2GP1 were recorded in 44/18 and 50/17 patients by ELISA and in 55/19 and 59/16 by CMA, respectively.IgA-aCL positivity was found in 35 (56%) of 63 patients. Thirty IgA-positive patients were positive for IgG-aCL by ELISA: 22 – IgG-aCL – highly positive, 6 – medium positive and 2 – low positive patients. IgM-aCL by ELISA was detected in 13 (37%) of 35 IgA-aCL positive patients: 11 – highly positive, 1 – medium positive and 1 – low positive. IgA-aCL was combined with IgG-aCL in 34 patients and with IgM-aCL in 16 patients in the CMA. IgG-aß2GP1 in ELISA was detected in 32 patients with IgA-aCL (24 –highly positive, 5 – medium positive and 3 – low positive) and in 34 – in CMA. IgM-aß2GP1 was combined with IgA-aß2GP1 with the same frequency in both methods (in 13 patients).IgA-aß2GP1 was detected in 30 (48%) of 63 patients. They were combined with both IgG-aCL and IgG-aß2GP1 in all cases in both methods. IgM-aCL and IgM-aß2GP1 were detected in 14 and 11 of 30 patients with IgA-aß2GP1, respectively. The combination of IgA-aß2GP1 with IgG-aCL by ELISA was in 27 (in most cases highly positive – 20) and with IgM-aCL – in 10 (highly positive - 8). IgG-aß2GP1 was detected in 28 patients with IgA-aß2GP1 (high positive – 21) and in 11 patients with IgM-aß2GP1 (high positive –7).IgG-aß2GP1-D1 was revealed in 48 (76%) patients. It was combined with IgG-aCL – in 38, with IgM-aCL – in 15 patients by the ELISA. The combination of IgG-aß2GP1-D1 by CMA was as follows: with IgG-aCL – in 46, with IgM-aCL – in 17, and with IgA-aCL – in 33 patients. In most cases, IgG-aß2gp1-D1 was combined with highly positive aCL levels. IgG-aß2GP1-D1 positivity was associated with IgG-aß2GP1 positivity in 42 – by ELISA and 47 – by CMA, IgМ-aβ2GP1 – in 13 and 14 patients by ELISA and CMA, respectively, and IgA-aß2GP1 – in 29. Isolated IgG-aß2GP1-D1 positivity was not observed.Conclusion:The frequency of IgA-aCL detection was 56% (35 patients out of 63), IgA-aβ2GP1 – 48% (30 patients out of 63), IgG-aβ2GP1-D1 – 76% (48 patients out of 63). There was not isolated positivity of this “extra” criterial antibodies. The presence of IgA-aCL, IgA-aβ2GP1, IgG-aβ2GP1-D1 was associated with highly positivity of IgG/IgM-aCL and IgG/IgM- aβ2GP1.Disclosure of Interests:None declared

Background:Antiphospholipid syndrome (APS) is an autoimmune disease often associated with severe, life-threatening vascular complications. The majority of patients (and in case of secondary APS, in 100% of cases) receive immunosuppressive therapy. Immunization with pneumococcal vaccines in patients with both primary APS (PAPS) and APS+SLE or secondary (sAPS) is necessary to prevent severe respiratory infections in these patients.Objectives:Purpose of the study - to study the tolerance and safety of 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with PAPS and sAPS.Methods:At this stage, the study included 28 patients with APS, of which 10 with PAPS, 18 with sAPS proceeding against the background of systemic lupus erythematosus (SLE), of which 23 women (82%), 5 men (18%). The average age (Me) of patients was 43 (35.5; 53.0) g. 20 patients received glucocorticoids (GC) 5-30 mg/day equivalent to prednisone, 17- hydroxychloroquine, 6- cytostatics (3-cyclophosphamide, 2-azathioprine, 1- mycophenolate mofetil), 8- biologics: 5-rituximab (RTM), 3-belimumab (BLM); 20-received anticoagulants (direct-10, indirect-10).1 dose (0.5 ml) of PPV-23 was administered subcutaneously. The follow-up time was 1 year in 23 patients and 5-5.5 months in 5-5.5 months. During the visits, standard clinical and laboratory tests were performed, immunological blood test and the level of antibodies to S.pneumoniaeResults:Vaccination was well tolerated in all patients. In 29% of cases, vaccine reactions of mild severity were observed: in 7 (25%) - a local reaction (pain in the arm for 1-3 days-at 7, redness up to 2 cm at the injection site-at 1), in 1 (3,6%), the patient experienced general weakness (moderately pronounced) for 1 month. Vaccinal reactions were completely reversible and did not require additional prescriptions. Post-vaccination complications develop, as a rule, in the first 1-2 months after vaccination. During the observation period, none of the patients had an exacerbation of the disease, reliably associated with the vaccination. There was no recurrence of thrombosis, both in patients receiving anticoagulant therapy and without it. No new autoimmune phenomena, both clinical and laboratory, were identified. The dynamics of the production of anti-streptococcal antibodies during the year was followed in 16 patients. One year after vaccination, 31% of patients showed a significant (more than 2-fold compared to the initial) increase in the concentration of antibodies to polysaccharides of the cell wall of S. pneumoniae (“responders”), 69% of patients were “non-responders” to the vaccine. At the same time, all 5 patients with PAPS were “non-responders”, and 45.5% “respondents” with sAPS.Conclusion:Preliminary results show that patients with APS tolerate PPV-23 vaccination well. In the next post-vaccination period, exacerbations of the disease, thrombosis were not recorded. Attention is drawn to the large number of “non-responders” in PAPS, however, to obtain statistically reliable results, it is necessary to continue the study and recruit more patients.Disclosure of Interests:None declared

Background:Immunosuppressive therapy increases the risk of pneumococcal infection in patients with systemic lupus erythematosus (SLE). The therapy, as well as some features of the course of the disease, can lead to a decrease in the immunogenicity of the pneumococcal vaccine in these patients.Objectives:The aim of the study was to identify “risk factors” that negatively affect the immunogenicity of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with SLE.Methods:The study included 60 patients aged 19 - 68 years with a reliable diagnosis of SLE, disease duration from 9 months. up to 42 years old. Nine patients had high disease activity, 12 had medium, 33 had low, and 6 had remission. Therapy: 58 patients received glucocorticoids (GC) 5-40 mg / day, 46-hydroxychloroquine, 33- cytostatics (CS), 23- biologics: 12-rituximab (RTM), 10-belimumab (BLM), 1- RTM and BLM. 1 dose (0.5 ml) of PPV-23 was administered subcutaneously. During the year, standard clinical and laboratory studies were carried out, the level of antibodies to polysaccharides of the S. pneumoniae cell wall in the blood serum was determined.Results:After 1-2 months. after vaccination, 78.7% of patients showed a more than twofold increase in protective antibodies, a year later - in 56.7% of patients (“responders”). The severity of the vac-cine response did not depend on age: in the subgroup of patients under 50 years of age (n = 46), the proportion of “responders” remained 52.2%, and in patients over 50 years of age (n = 14) -50%. With different duration of the disease, the vaccine response did not differ significantly: with a disease period of up to 5 years, the vaccine response was observed in 47.6%, from 5 to 10 years - in 66.7%, over 10 years - in 55.6% of patients. Patients in remission had the lowest vaccine response (33.3%), while with high SLE activity, 100% response to the vaccine was recorded (p = 0.02), which is probably due to the fact that remission requires long-term and active immunosuppressive therapy, and patients with high activity such therapy has just been initiated or is to be. With an average and low degree of activity, the number of “respondents” was the same (50% and 51.5%, respectively). In patients receiving biologics therapy, a full-fledged vaccine response was observed less frequently than in patients without biologics (39% and 68%, respectively, p = 0.03), while no differences were found against the background of RTM and BLM therapy (41.6% and 40% of “respondents”, respectively). The effect of the duration of biologics therapy on the severity of the vaccine response was analyzed.There was a tendency for the predominance of “responders” in the group with a duration of therapy before vaccination up to 1 year, as well as in the group of initiation of biologics after vaccination, however, the differences were not statistically significant.Conclusion:RTM and BLM have a negative effect on the immunogenicity of the PPV-23 vaccine. However, if the timing of administration is observed (initiation of biologics therapy after vaccination or vaccination against the background of biologics therapy lasting less than a year), the number of “responders” increases. Further recruitment of patients is needed to clarify and confirm the results obtained.Disclosure of Interests:None declared

Background:In more than 40% of cases, systemic lupus erythematosus (SLE) is associated with the presence of highly positive antiphospholipid antibodies, with 50-70% of patients developing antiphospholipid syndrome (APS) over the next 10 years of the disease. Both diseases have similar and different clinical manifestations of skin lesions. The variety of skin lesions in SLE and APS requires a differential diagnosis and can make it difficult to diagnose a systemic autoimmune disease in a timely manner.Objectives:To study the frequency of skin manifestations in SLE and APS, depending on the positivity of aPL.Methods:The study included 116 patients with SLE (104 women and 12 men), mean age 37.9±12.9, disease duration 8.5 [1.15-13.0]; 40 patients with APS (33 women and 7 men), mean age 36.2±9.39. All patients were evaluated for skin lesions, and patients with APS were determined by IgG/IgM-aCL and IgG/IgM-aß2HP1 by enzyme immunoassay (ELISA), 19 of them were determined by IgA-aCL, IgA-aß2HP1 and IgG-aß2HP1-D1 chemiluminescence analysis (CMA).Results:Acute skin lesions in past history were noted in 58 (50%) patients, chronic lesions -I n 21 (18.1%) patients; photosensivity and alopecia were indicated in 46 (39.6%) patients, mucosal lesions were noted in 36 (31%) of 116 patients, which corresponds to the literature data on the frequency of skin lesions and its appendages in SLE. At the time of inclusion in the study, skin lesions were detected in 20 patients. Score according to the CLASI index in patients with skin lesions: activity index=1.55 [0-22]; damage index=1.81 [0-36].Skin lesions are the second most common signs of SLE onset (debut in 26 (22.4%) patients), second only to arthritis (38 (32.5%) patients), while the detection of immunological disorders (highly positive ab to dsDNA) was observed in 7 patients (6%) with reliable APS and probable SLE, who may not have had time to develop a clinic for reliable SLE.Livedo, as one of the most frequent skin manifestations of APS, was detected in 60 patients and was significantly associated with IgM-aCL and IgM-aß2HP1 positivity (pThe development of ulcerative-necrotic vasculitis with deep skin necrosis was observed in 3 patients, 2 of them were highly positive for IgG-aCL, IgG-aß2HP1, IgG-aß2HP1-D1. Melanoma was detected in the past history in 2 patients with highly positive for IgG-aCL, which is not a manifestation of the underlying disease, but confirms an increased risk of malignancy with aPL-positivity.Conclusion:More than half of the patients had acute skin lesions, and about a quarter of the cases had skin lesions at the onset of the disease. The presence of comminuted hemorrhages was associated with positivity of IgG-aCL, IgG-aß2HP1, IgG-aß2HP1-D1) and IgA-aCL. Assessment of skin activity and damage (in particular, according to the CLASI index) is necessary for a comprehensive analysis of the dynamics of the disease and the response to therapy. The detection of aPL is necessary not only for the purpose of predicting thrombotic catastrophes, but also for the development of skin manifestations of APS.Disclosure of Interests:None declared

Background:Vaccination of patients with autoimmune diseases with pneumococcal vaccines is necessary to prevent severe respiratory infections in this group of patients. The main issue of immunization of patients with systemic lupus erythematosus (SLE) remains the issue of safety.Objectives:The aim of the study was to study the safety of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with SLE.Methods:The study included 73 patients with a reliable diagnosis of SLE, of which women - 64, men - 9, aged 19 - 68 years. 69 patients received glucocorticoids (GC) 5-30 mg/day, 55- hydroxychloroquine (GCH), 37-cytostatics (CS), 27 – biologics (14 – rituximab (RTM), 11 – belimumab (BLM), 2-BLM and RTM). 1 dose (0.5 ml) of PPV23 was administered subcutaneously. 60 patients were examined within 1 year, 13 - within 2-3 months.Results:Vaccination tolerance was assessed in 73 patients: in 33 (45.2%) - vaccine reactions were absent, in 36 (49.3%) - local reactions of mild and moderate severity were noted (pain, swelling, skin hyperemia at the injection site of the vaccine), lasting from 2 to 7 days, in 1 (1.4%) - general weakness within 1 month, in 2 (2.7%) - mild diarrhea within 1 day. Vaccinal reactions were typical and completely reversible, did not require additional appointments. One patient (1.4%) developed a hyperergic reaction of the Artyus phenomenon type, which was arrested within 7 days by the use of antihistamines and topical GCs. None of the 60 patients, whose follow-up period was 1 year, had no exacerbations of the disease directly related to vaccination (i.e., in the next 2-3 months). Vaccination was carried out both at a low degree of activity (n = 33 (55%)) and remission (n = 6 (10%)), and at an average (n = 12 (20%)) and high (n = 9 (15%))) the degree of SLE activity. The dynamics of the SLE activity index SLEDAI-2k (Me) during the year was as follows: initially - 4 (2; 6), after 2-3 months - 2 (2; 4), after 12 months - 2 (2; 4). During the year, 7 out of 60 patients had a moderate exacerbation of the disease, which was not related to the vaccination in terms of timing: after 3.5-5 months (3), 12 months (4). An exacerbation occurred in 4 - with a decrease in the HA dose, in 1 - after psychological stress, in 1 - against the background of persistently high immunological activity and insufficient therapy, in 1 - without an increase in immunological activity. In 4 out of 7, exacerbation was manifested by skin rashes and articular syndrome, in 1 - by the development of panniculitis, in 2 - by leukopenia. All these symptoms were noted earlier in the period of exacerbation. In all, the exacerbation was quickly stopped by a moderate increase in the HA dose. In 60 patients, the dynamics of immunological markers of SLE was analyzed during the year after vaccination. There was no evidence of a significant increase in the immunological activity of SLE after vaccination with PPV-23. After vaccination, no new autoimmune phenomena have been identified. In the first 3 months. after vaccination, in isolated cases, there was a transient increase / decrease in SLE markers (a-DNA, ANF, C3, C4) with a subsequent return to the initial values, without symptoms of exacerbation of the disease.Conclusion:1. During the year of observation, no exacerbations were observed that were reliably associated with vaccination. 2. Vaccination with PPV-23 is safe for SLE patients during periods of low and moderate activity. If necessary, vaccination is possible at high activity without the development of adverse events. 3. The multidirectional dynamics of the main markers of SLE observed during the year reflects the instability of immunological parameters characteristic of SLE.Disclosure of Interests:None declared

Background:Cognitive impairment (CI) in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) patients have been poorly described and recognized.Objectives:to describe the rates and spectrum of CI in primary (PAPS) and secondary to systemic lupus erythematosus (SLE) (SAPS) APS patientsMethods:113 patients (70 with APS (37 – PAPS, 33 – SAPS) and 43 - SLE without APS), 89 (78,8%) – women, were consecutively enrolled in the study. The mean (M±SD) age was 37,9±11,9 years. SLE activity was measured by SLEDAI scale. Mental disorders (MD) were diagnosed by psychiatrist in accordance with ICI-10 in semi-structured interview. CI were diagnosed with psychology and neuropsychology methodsResults:CI of varying severity were found in 105 (92,9%) patients: 62,9% - mild, 23,8% - moderate and 13,3% - severe. Severe and moderate CI were more associated with APS (48,6% in PAPS and 39,5% in SAPS vs 18,6% in SLE, p=0,004 and p=0,04, accordingly). CI were predominantly organic origin in all patients, but vascular dementia was detected only among patients with APS (10,8% of PAPS and 3,03% of SAPS patients). There was no association of CI with clinical manifestations and SLE activity. In patients with PAPS CI was associated with stroke, livedo reticularis and lupus anticoagulant positivity. In 84 patients (74,3%) CI were also specifically bounded to MD. Current MD were detected in 100 (88,5%) patients: schizotypal disorder was found in 10 (8,85%) patients and was associated with PAPS (13,5% vs 9,09% in SAPS and 4,65% in SLE); anxiety-depressive spectrum disorders (ADDs) - in 95 (84,1%) (chronic and recurrent depression prevailed 37 (32,7%) and 42 (37,2%) resp.); the structure of MDs in accordance with ICI-10 differed slightly between groups, but no statistically significant differences were obtained.Conclusion:сognitive impairment, mainly of an organic type, are characteristic of most patients with SLE and APS. The significant associations of сognitive impairment with clinical manifestations and activity of SLE were not identified, but patients with сognitive impairments were more likely to have anxiety and depressive disorders, strokes, livedo reticularis and lupus anticoagulant positivityDisclosure of Interests:None declared

Background:Classification criteria for SLE need validation and selection of the most advanced ones for clinical practiceObjectives:To validate Systemic Lupus International Collaborating Clinics (SLICC)-12, American College of Rheumatology (ACR)-97 and 2019 European League against Rheumatism/American College of Rheumatology (EULAR/ACR-2019) for SystemicLupus Erythematosus classification criteria on a patient cohort from V.A. Nasonova Scientific Research Institute of Rheumatology (Moscow)Methods:This prospective study included 252 (n=152 with SLE and n=100 non SLE: 74 – with systemic sclerosis (SC) and 26 – with primary antiphospholipid syndrome (pAPS)) patients who were sequentially admitted to the 4th Rheumatology Department from December 2018 to June 2020. All of the patient records were reevaluated by expert rheumatologist in order to determine if they agree with the diagnosis. For every patient, a check-list of SLE-related features was filled out. The association between clinical diagnosis and diagnosis generated on the basis of ACR-97, SLICC-12 and EULAR/ACR-2019classification criteria was assessed. The overall sensitivity and specificity of ACR-97, SLICC-12 and EULAR/ACR-2019 classifications, as well as the sensitivity and specificity according to disease duration was calculated. The predictive value of every criterion in ACR-97, SLICC-12 and 2019 EULAR/ACR classification was assessed using logistic regression analysis and receiver operating characteristic (ROC) curves.Results:According to ACR-97 criteria, reliable SLE was diagnosed in 131 (86%), according to SLICC-2012 – in 145 (95.3%) and according to EULAR/ACR-2019 – in 144 (94.7%) of 152 patients, respectively. We identified the criteria that were significantly more represented in the SLE-group. The sensitivity and specificity (Table 1) did not change depending on the ANA titers (1/160 and 1/320) and the duration of the disease.Table 1.The sensitivity and specificity of SLE criteria in 152 SLE patients and 100 non SLE patientsSLE classification criteriaAUC, 95% CICut pointSensivitySpecifityACR-970.654 (0.550-0.758)489.736SLICC-120.616 (0.505-0.728)493.1432019 EULAR/ACR0.609 (0.492-0.727)10*97.448Note. ACR-97 – American College of Rheumatology classification from 1997; SlICC-12 – Systemic lupus International Collaboration Clinics classification from 2012; 2019 European League Against Rheumatism/American College of Rheumatology. ANA – anti-nuclear antibody more than 1/320 n=116; ANA < 320 n= 36. AUC – area under the ROC curve; Cut point - reference point for the number of criteria, * number of points ≥ 10.When excluding patients with SC in a single-factor logistic model of patients with SLE and pAPS, indicating the number of criteria, the sensitivity was for ACR-97 - 86, for SlICC-12 - 95, for 2019 EULAR/ACR - 95, the specificity was 100, 62 and 62, respectively.Conclusion:Evaluation of the criteria by level ANA revealed the highest sensitivity for 2019 EULAR/ACR and SLICC-12, the specificity was low for all three criteria. In the analysis of patients with SLE and pAPS, the sensitivity was highest for 2019 EULAR/ACR and SLICC-12, the specificity was 100 for ACR-97.Disclosure of Interests:None declared

Background:Whereas antiphospholipid syndrome (APS) is a non-inflammatory vasculopathy and is associated with thrombosis in 98% of cases, Behcet’s disease (BD) is a systemic vasculitis of unknown etiology, characterized by vascular damage of any calibre. Both venous and arterial thromboses occur in 45% of BD patients and are associated not with hypercoagulable disease but with inflammatory changes in the vascular wall mediated by hypersecretion of pro-inflammatory cytokines and endothelial cells dysfunction. Thrombodynamics (TD) is a new global test for diagnosing plasma haemostasis disorders, identifying bleeding and thrombosis risks, and can be used to detect a prothrombotic state and assess the influence of disease activity and course on the hypercoagulation process.Objectives:comparative assessment of TD in patients with APS and BD before anticoagulant therapy (AC).Methods:The study included 20 patients (9 APS and 11 BD) and 8 age and sex-matched healthy controls (HC). None of the subjects received AC. Thromboses in past history were registered in 5/9 (55%) APS patients and 2/11 (18%) BD patients and none of HC. Fetal loss occurred only in women with APS (4/4 (100%) who had pregnancy during the disease). All the patients were hospitalized and underwent fool investigation according to the diagnosis including TD, local coagulation tests and antiphospholipid antibodies profile.Results:the velocity of clot growth in APS was lower, than in BD and in HC: 23.7 [22.6; 24.7] vs 29.0 [28.2; 34.4] and 31.1 [28.9; 33.5] Um/min, respectively (р=0.001). Clot size at 30 minutes in APS also was lower, than in BD and HC: 972.1 [921.3; 1007.4] vs 1152.7 [1098.3; 1225.4] and 1226.6 [1140.5; 1295.1] Um, respectively (р=0.001). Spontaneous clotting was registered only in 2 BD patients in mean time 2 minutes. Clot density and lag time (Tlag, the delay between the test start and the onset of clot formation) were the same in all three groups. Prolonged APTT was found in APS (33.7 [30.6; 47.1] sec) and normal APTT - in BD (30.9 [29.1; 31.1] sec) and HC (29.7 [28.2; 30.8] sec). Increased soluble fibrin-monomer complexes were revealed in all APS patients (100%), 91% BD patients and 25% HC (р=0.01). After interpretation the TD results were distributed as follows: hypocoagulation was noted in 1 APS patient with a positive lupus anticoagulant, while all other APS patients had normocoagulation. Thrombotic readiness status (TRS) was diagnosed only in 2 BD patients. The frequency of normocoagulation and hypercoagulation did not differ between BD and HC. Local coagulation tests (APTT, thrombin time, prothrombin time) were the same depending on hypo- and hypercoagulation by TD results. Fibrinogen level in BD patients with hypercoagulation was higher, than in BD patients with normocoagulation and TRS: 4.2 [3.6; 4.7] vs 2.8 [2.7; 3.0] and 2.8 [2.7;2.8] g/l respectively, р=0.04. BD activity by Behcet’s Disease Current Activity Form correlated with stationary velocity of clot growth (Rs = 0.68, pConclusion:Thrombodynamics results showed: before anticoagulant therapy there were normocoagulation with a tendency to hypocoagulation in APS and hypercoagulation in BD. In BD hypercoagulation associated with disease activity.Disclosure of Interests:None declared

Background:The role of antiphospholipid syndrome (APS) as a cause of chronic organ damage in patients with systemic lupus erythematosus (SLE) is important. While acute disease manifestations of APS are well known, information on the long-term prognosis and damage in affected patients is still very limited.Objectives:Тo assess the severity of organ damage in patients with APS without SLE and with concomitant SLE, as well as the feature of irreversible damage to internal organs in patients with primary APS during a dynamic observation using SLICC/ACR Damage Index (SDI).Methods:Тhe study included 195 patients (41 men and 154 women) who were observed at the Institute of Rheumatology from 2007 to June 2018 with a diagnosis of SLE and APS. The study inclusion criteria were: a follow-up period of at least 3 years with the study of serological markers of APS for previous years, the possibility of dynamic monitoring of patients, patient consent. Patients were divided into 3 groups, depending on presence of APS: group I -SLE with APS (n=99 with average age 34.6 [25-44), group II - SLE without APS (n=45; 33.5[26-42]) and group III - 45 (average age 37.7 [27-46]) patients with primary APS (PAPS) diagnosed according to international diagnostic criteria, without signs of any disease. In all three groups organ damage was assessed using SDI. SDI 1-2 points corresponded to moderate damage, more than 2 points - to severe.Results:A linear increase in irreversible organ damage was noted over 10 years of follow-up. At the time of inclusion in the study, the average SDI was significantly higher in the SLE + APS group than in the SLE group: 1.32 versus 0 when included (p Conclusion:APS is an independent predictor of increased SDI. The determination of irreversible organ damage in patients with PAPS using SDI allows us to assess the functional disorders of organs and systems and can be used in clinical practice in these patients.Disclosure of Interests:None declared

Background:Vaccination with 23-valent polysaccharide pneumococcal vaccine (PPV-23) in systemic lupus erythematosus (SLE) provides the prevention of severe respiratory infections in patients receiving immunosuppressive therapy. The importance of this vaccination significantly increases before and during treatment with biologics.Objectives:The aim of the study was to evaluate the immunogenicity of PPV-23 in SLE patients.Methods:The study included 52 patients with SLE, including 44 women and 8 men, aged 19 to 68 years. The duration of the disease varied from 9 months to 39 years. At the time of vaccination 7 patients had high, 10 – moderate, 30 – low activity of the disease according to SLEDAI 2K, and 5 had remission. 50 patients received glucocorticoids (GC) 5-30 mg/day equivalent to prednisone, 39 – hydroxychloroquine (GCH), 29 – cytostatics (CS), 20 – biologics: 10 – rituximab (RTM), 10 – belimumab (BLM). 1 dose (0.5 ml) of PPV23 was administered subcutaneously. During the visits, standard clinical and laboratory tests were performed, and the level of antibodies (Ab) to S.pneumoniae in blood serum was determined (VaccZymeTMPCPIg 2 kits – The Binding Site Ltd, Birmingham, UK).Results:In 1-2 months after the vaccination 78.7% of patients had a significant (more than 2 times compared to baseline) increase in the concentration of Ab to the pneumococcal cell wall polysaccharides. A year after vaccination, 61.5% of patients (“responders”) had a significant increase in the concentration of anti-pneumococcal Ab. 20 (38.5%) of 52 patients were considered “non-responders”. Median concentration of anti-pneumococcal Ab was 67[42.6; 105.8] mg/l at visit 1 (initially), 405[143.5; 468.4] mg/l at visit 2 (in 1-2 months), 166.9[77.5; 377.4] mg/l at visit 3 (in 12 months).There were clear differences in the degree of the vaccinal response depending on the therapy: in 20 patients receiving biologics full vaccinal response was achieved significantly less frequently than in patients who did not receive these drugs (40% and 75%, respectively), p=0.02. There were no obvious differences in the vaccinal response during treatment with RTM and BLM (40% of responders in both groups). The vaccinal response significantly decreased during treatment with biologics in combination with GC+/ - GCH (50% of responders). The lowest vaccinal response was observed in patients receiving biologics in combination with GC and CS + / - GCH (33.3% of responders).The analysis of the degree of the vaccinal response depending on the timing of vaccination and the time of biologics infusion was carried out. In the first group (n=6), vaccination was carried out at the optimal time in accordance with the recommendations of EULAR (2020). In the second group (n=14) vaccination was carried out in suboptimal time: during regular treatment with BLM (n=6), 1 week before the next introduction of RTM (n=2), 3-5 months after the last introduction of RTM (5), 1 week before the next introduction of RTM (n=1), 20 days after the BLM termination (n=1). In the first group with optimal vaccination terms, the number of responders was 66.7%, in the second group with suboptimal terms – 28.6%, p=0.27.Conclusion:Sufficient immunogenicity of PPV-23 was shown in SLE patients receiving immunosuppressive therapy. The negative impact of biologics on the vaccinal response was confirmed, especially if the vaccination was not performed at the optimal time in relation to the infusion of the drug or during monthly administration of BLM. If optimal vaccination terms are maintained during the treatment with or initiation of biologics (6 months after the last administration of RTM and 1 month before the next (or first) administration of RTM, 4 months after the last and 1 month before the next (or first) administration of BLM), the number of responders increases significantly. The lowest vaccinal response was obtained in patients receiving combined immunosuppressive therapy with biologics + GC+CS.Disclosure of Interests:None declared

Background The development of a variety of neuropsychiatric symptoms in SLE patients starts with the dysregulation of the immune system. Involvement of the CNS in the pathological process during the onset of the disease can significantly worsen the patient‘s condition and complicate the prognosis. Objectives To study the features of neurological manifestations of SLE in the Kyrgyz cohort of patients. Methods The basis of the study were the results of an initial examination of 460 patients with prospective observation, with a reliable diagnosis of SLE. Out of them, 112 patients were neurological, at the age of 30 (median) [26, 41], predominantly of Kyrgyz nationality (87), with duration of the disease from 6 months to 7 years (median – 2.0) treated in the National Cardiology and Therapy Centre named after M. Mirrakhimov (NCTC) from January 2012 to December 2017. Neurologic manifestations of SLE were diagnosed by clinical examination by a neurologist using some instrumental methods of investigation. To assess the neuropsychiatric state of patients, the classification criteria by the American College of Rheumatology (1999) were used. Neuropsychiatric disorders were diagnosed through a clinical examination by the psychotherapist using the classification of mental disorders and behavioural disorders according to ICD (International Classification of Diseases)−10. Results The damage of the nervous system was observed in 112 (24,305%) Kyrgyz patients from 460, mainly of the central nervous system – in 77 (68.75%), to a lesser extent – the peripheral nervous system (PNS) – in 35 (31.25%) out of 112. In half of the observed patients with CNS lesions, various neuropsychiatric disorders were registered – in 39 (50.65%) out of 77, with psychosis prevalence with visual and auditory hallucinatory syndrome – in 34 (87.18%) out of 39 patients. There were 14 patients with cerebrovascular infection (18.18%) out of 77, mainly with ischaemic stroke in the SMA basin. There was one patient with aseptic meningoencephalitis with manifestations of mild hemiparesis and with the disruption of the function of the pelvic organs in the form of mandatory urges. Symptoms of myelopathy with malfunction of the pelvic organs were registered in 9 (11.69%) patients out of 77. Five patients had symptoms of combined CNS and PNS lesions. In one of them cases the patient had encephalopolyneuroradiculopathy of the Guillain-Barre type with the phenomena of coarse tetraparesis and with disruption of the function of pelvic organs in the form of delay, with a single epicprism. Conclusions Neurological manifestations of SLE in the majority of Kyrgyz patients were mainly caused by CNS lesions (68.75%), mostly in the form of neuropsychiatric disorders (50.65%), with a predominance of psychosis with visual and auditory hallucinatory syndrome (87.18%). Disclosure of Interest None declared

Background HHC may be additional factor of thrombosis in SLE patients Objectives To assess the role of HHC as additional risk factors in development of vascular complications in SLE and antiphospholipid syndrome (APS). Methods A total of 125 patients (24 M and 101 F, mean age 38±13 years and the disease duration 14±11 years) were divided into three groups: group 1 – SLE patients (n=51); group 2 – SLE +APS patients (n=49); group 3 – primary APS patients (n=25). Homocystein (HC) was assayed by high performance liquid chromatography. DNA diagnostics by the method of polymerase chain reaction was used to determine gene mutation C677T methylenetetrahydrofolate (MTHFR) reductase in 93 out of 125 patients. Results HHC (HC >15 mcg/L) was diagnosed in 82 of 125 (66%) patients: in 59% patients of group 1, 67% – of group 2% and 76% – of group 3. There was a relationship between HHC and digital necrosis (DN): 80% of patients with DN had HHC while HHC was in 57% patients without DN (c 2 =4.76, p=0.03). Elevated level of HC was registered in 43 of 55 (78%) APS patients with thromboses vs. 9 of 19 (47%) aPL-positive SLE patients without thromboses (p=0.03). HHC occurred significantly more frequently in patients with arterial thromboses (in all 14 patients) than in patients with venous thromboses – in 16 of 23 (69.9%) pts (p=0.03) and in the absence of thromboses (p=0.04). HHC was associated with thromboses of cerebral (in 90%), peripheral arteries (in 84%) and myocardial infarction (in 79%) vs. 47% of patients without thromboses (p=0.005; p=0.04, p=0.04 respectively), (79 vs. 47%,). Mutation of C677T MTHFR was revealed in 33.3% of SLE patients, in 57.7% – of SLE +APS and in 63.2% – PAPS. Mutation C677T in the gene MTHFR was detected in 57% of examined patients, 20% of them had homozygous variant and 80% are heterozygous. Patients with a homozygous C677T MTHFR gene was observed the tendency to develop arterial thrombosis Conclusions More than 50% APS pts had elevated level of HC as additional thromboses factors. Correlation between HHC and thromboses, primarily arterial, in APS patients gives grounds for the role of HHC in development of vascular complications in SLE and APS pts. Disclosure of Interest None declared

Background The purpose of this study was to compare incidences of VTE in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) after total hip arthroplasty, different strategies for prevention of VTE and evaluate their efficiency. Objectives To evaluate the efficiency of prevention of VTE in patients with rheumatoid arthritis and osteoarthritis after total hip replacement under comparable conditions. Methods A one-year prospective cohort study was performed on 173 primary THA patients operated in V.A. Nasonova Research Institute of Rheumatology for the period 2016. Of these, 91 patients with RA (52.6%) and 82 patients with OA (47.4%). For a comparative analysis of the efficiency of anticoagulant therapy, each patient group was divided into 2 subgroups by type of drug therapy. The first - nadroparin calcium (the drug therapy was started for 12 hours after the operation at a dose of 0.1 ml per 10 kg of body weight one time per day), the second - nadroparin calcium with transfer to dabigatran etexilate (the first stage of 4 hours after the operation was started therapy by nadroparin calcium, and then after the removal of the epidural catheter moved to the dabigatran etexilate).Doppler ultrasonography (DUS) was routinely performed preoperatively and on postoperative day 7, 14, then 1 time a month for diagnosing a deep venous thrombosis (DVT). Time of observation was 6 months. Results DVT were reported in 8 (4.8%) patients, 2 of them (1.2%) with RA and 6 (3.4%) with OA. Distal DVT developed on 8 and 17 days after total hip replacement in RA patient9s group. They received nadroparin calcium only. 5 patients with VTE after surgery from OA group used nadroparin calcium and 1 patient was on combined drug therapy. Of the 8 cases of VTE - 6 (75%) were asymptomatic and 2 (25%) with development of clinical and laboratory picture. All cases of thrombosis in a group of RA was asymptomatic. In a perioperative period of clinically significant bleeding was not seen. Conclusions Cases of VTE in patients with RA, despite the large number of risk factors, under comparable conditions is significantly lower than patients with OA. The number of asymptomatic DVT dominates symptomatic both comparison groups. In patients with RA and OA who were from the first group have reported 6 cases of VTE and only 1 case of VTE have reported in patients who were from second group. Prevention of VTE by combination of LMWH and NOACs was more effective and safety in RA and OA patients. Disclosure of Interest None declared

Background Antiphospholipid syndrome (APS) is an acquired thrombophilia characterized by reccurent venous and arterial thrombosis, obstetric pathology (fetal loss), and synthesis of antiphospholipid antibodies. Warfarin is a “golden” standard of APS therapy. However it has number of disadvantages. Dabigatran etexilate is a direct thrombin inhibitor and its main differences from warfarin are fixed dose, no need of regular INR monitoring,less elimination half-life. Objectives To evaluate efficacy and safety of dabigatran etexilate in patients with APS. Methods 38 patients (pts) (F:26, M:12) with primary and secondary APS, 37,2±9,9 years old. 24 pts with primary APS, 14 pts with secondary APS: 13 had systemic lupus erythematosus (SLE) + APS, 1 rheumathoid arthritis (RA) + APS. The diagnosis of APS was established due to international APS criteria (Sydney), SLE – SLICC 2012, RA - ACR/EULAR 2010. The majority number of pts (n=28) received warfarin, others – sulodexide (n=1), low molecular heparin (n=1), had no anticoagulant therapy (n=3), 5 pts received dabigatran etexilate before inclusion to trial. The control of coagulogram was done 3 times: before inclusion to trial, in 24 weeks and in 48 weeks after inclusion. Trial assays were performed in the laboratory in V.A. Nasonova Research Institute of Rheumatology, Moscow, Russian Federation. APPT and thrombin time tests were done with the automated coagulometer Coalysys Plus C (Behnk Electronic, Germany); thrombin time test was done with STA-thrombin reagent (Diagnostica Stago, France), APPT with STA-Cephascreen reagent (Diagnostica Stago, France). Lupus anticoagulant was assessed by the dilute Russell9s viper venom time, using Siemens Healthcare (Germany) LA1 (screening) and LA2 (confirmation). IgG or IgM antibodies against cardiolipin and β2 glycoprotein I (β2GPI) were measured with automated enzyme-immunoassay analyzer Alegria with Anti-Cardiolipin IgG/IgM and Anti-beta-2-Glycoprotein I IgG/IgM reagents (Orgentec Diagnostika GmbH, Germany). Triple positivity was defined as positive antibodies against cardiolipin and β2GPI and a positive test for lupus anticoagulant. Results 32 pts had high or medium level of aPL (anticardiolipin antibodies IgG,IgM, anti-β2glycoprotein antibodies IgG,IgM), 6 had low or normal level of aPL. 12 pts were triple positive. APPT and thrombin time before inclusion to trial were 44,2 [36,5;53,5] and 16,1 [14,9;17,0], on 24 week after dabigatran etexilate start 51,0 [40,5;65,7] and 163,5 [108,7;240,0] and on 48 week 58,7 [45,6;63,2] and 194,1 [152,6;255,2] respectively.1 patient was excluded due to non-compliance. During follow-up period from 1,5 to 12 (10,6±3,2) months 7 pts (22,6%, 20,7 per 100 patient-years) experienced reccurent thrombosis including superficial vein thrombosis (n=2; 6,5%, 5,9 per 100 patient-years), thrombosis of paranephric veins (n=1; 3,2%, 2,9 per 100 patient-years), acute cerebrovascular disorders (n=4; 12,9%, 11,8 per 100 patient-years). All pts with reccurent thrombosis had high or medium level of aPL; 2/7 were triple positive, both had acute cerebrovascular disorders. 5 pts (16,1%, 14,8 per 100 patient-years) experienced bleeding: 2 hemorrhoidal bleedings, 1 uterine bleeding, 2 nasal bleedings. There was no case of severe bleeding. Conclusions Dabigatran etexilate could be used in patients with APS in the case of warfarin non-effectiveness. These findings need to be confirmed in larger studies. Disclosure of Interest None declared

Background and aims There are no data regarding the real-life picture of SLE in Kyrgyzstan. Methods In a prospective observation included 325 patients with SLE, who were treated in NCCIM (2012 - 2016). Majority of these patients (301) were young women (median - 27 [25;41]), primarily Kyrgyz (284), with disease duration of 3 (median-3,0 [0.7;8.0]) years. Assessed SLEDAI 2K and SDI. Results They were mostly patients with acute variant of SLE-129 (39.7%), 127 (39.08%) were with high and 86 (26.46%) with very high activity. Most of the patients - 283 (87.1%) were registered with immunological activity. In most cases of the desease were: skin lesions (97.23%), serous membrane lesions (65.54%) and kidney lesions (59.38%). The neurological symptoms was noted in 120 patients (36.92%): 99 of 120 patients (82.5%) had a significant CNS lesions; 32 patients of 99 (32.3%) had neuropsychiatric disorders, 27 of these patients had visual and auditory hallucinatory syndrome. Respiratory disorders occurred in 60 (18.46%) patients. The vast majority of these patients were with pulmonary arterial hypertension (46.66%). Acute lupus pneumonitis was detected in 23 (38.33%) patients. At the onset of the study, SDI was identified in 65 patients (20%). These were mainly patients with irreversible changes in the kidney (30,8%), associated with taking GC (27.7%). Conclusions Acute onset of the disease (39.7%) was noted in most Kyrgyz patients. 97.23% of those ones with primary skin lesions, 65.54% with serous membrane lesions and 59.38% with kidney lesions, 39.92% patients had various neurological symptoms, 32.3% of these patients had serious neuropsychiatric disorders.

Contexte Les anticoagulants oraux directs (AODs) sont indiques en prevention secondaire de la maladie veineuse thromboembolique, cependant leur efficacite n’a pas ete evaluee specifiquement dans le sous-groupe des patients atteints d’un syndrome des antiphospholipides (SAPL). Deux essais controles randomises montrent des resultats contradictoires au sein de cette population de patients. Objet de la revue Nous avons conduit une revue systematique de la litterature utilisant les databases Medline, Cochrane et Embase, de 2000 a 2018 interessant les patients SAPL traites par AODs. Nous avons realise une analyse sur donnees individuelles afin d’estimer la prevalence des recurrences thrombotiques chez les patients SAPL traites par AOD au sein de la litterature et d’identifier les facteurs predictifs d’une recidive thrombotique. Resultats Notre revue systematique a identifie 447 patients traites par AODs publies dans 47 etudes ; parmi eux, 73 ont presente une recidive thrombotique (16 %). La duree moyenne avant recidive etait de 12,5 mois. Les trois AODs utilises etaient le rivaroxaban (n = 290), le dabigatran etexilate (n = 144) et l’apixaban (n = 13). Il n’y avait pas de difference significative de taux de recidive thrombotique entre l’utilisation d’antiXa ou de dabigatran etexilate (respectivement 16,9 % et 15 %). La triple positivite (positivite des trois criteres biologiques du SAPL) etait associee a une multiplication du risque de recidive thrombotique par 4 (56 % versus 23 %, OR = 4,3 [IC 95 % 2,3–7,7], p Il n’y avait pas de difference significative de recidive selon le caractere primaire ou secondaire du SAPL. En conclusion, les AODs doivent etre utilises avec precaution chez les patients SAPL, certains patients semblant a haut risque de recidive. Des essais cliniques utilisant un critere de jugement principal clinique d’efficacite et de securite sont en cours. Dans le meme temps, un registre de suivi des patients SAPL traites pas AODs peut etre propose afin d’etablir chez quels sous-groupes de patients SAPL, les AODs pourraient etre une alternative aux AVK.

Background Systemic lupus erythematosus (SLE) is a devastating disease affecting different organs, ultimately leading to organ failure and death. To date, there are no data regarding the real-life picture of SLE in Kyrgyzstan. Objectives To study of clinical symptoms, course and outcome of SLE according to the prospective study among residents of Kyrgyzstan. Methods An 2-year prospective analysis of patients with SLE with a specially developed research base (BLIPS 8, ADS-Limathon). 60 patients with definite diagnosis of SLE (ACR, 1997; SLICC, 2012), were treated in the department of rheumatology of NCCIM and observed from 2012 to 2015. They were evaluated by sex, age, disease duration, activity of SLE according the SLEDAI-2K, irreversible organ damage by SLICC Damage Index (SDI), quality of life using the SF-36 questionnaire, LupusQoL, HADS, FACIT, therapy, with monitoring of all parameters every six months for 2 years. From the data of the immunological studies immune linear (immunoblot) “ANA-LIA-Max 17” were analyzed with a purpose of detecting the antibodies of double-stranded DNA, Sm D1 antigen and antibodies of double-stranded DNA-linked immunosorbent analyisis (ELISA), C3-C4 components complement, indirect immunofluorescence of the antinuclear antibody cells of line Hep-2. Results Patients were mainly from the northern region of the republic (81.7%). The vast majority were women (86.7%), with average age 30 years old, with disease duration of about 1.0 years. Periods to verify the diagnosis ranged from 1 month to 9 years. The clinical course was dominated by patients with acute version (47%) and high activity (57%). In the debut of the disease most common clinical symptoms were cutaneous and articular syndrome (84.2% and 72.3%, respectively), the defeat of the serous membranes (88%) and kidney (68%). All patients received glucocorticoids (GC), 79% of them in the form of pulse therapy with methylprednisolone. From immunosuppressive drugs most commonly were used CP (48%), AZA (21%), MTX (10.4%) and plaquenil (11%), to a lesser extent MMF (8%). The proportion of patients receiving biologic therapy (rituximab) was only 2%, IVIG (Octagam) - 3.3%.The development of irreversible organ damage was recorded in half the patients (46%), at average of 6 months from the onset of the disease, mostly with low (36.7%) and the average SDI (21.7%). During the period of 2-year prospective study not only a significant reduction in the activity of the pathological process in many patients (p Conclusions In the debut of the SLE acute onset and high disease activity, which led to the rapid development of organ damage in half the patients was recorded. In the structure of mortality among Kyrgyz cohort of SLE patients with renal involvement prevailed, CNS and CNS combined with lungs. Disclosure of Interest None declared

Background Systemic lupus erythematosus (SLE) is a devastating disease affecting different organs, ultimately leading to organ failure and death. To date, there are no data regarding the real-life picture of SLE in Kyrgyzstan. Objectives To define retrospectively the pattern of clinical features, disease course and outcome of patients with SLE in Kyrgyzstan. Methods The retrospective study comprised of 107 consecutive patients with confirmed SLE, who underwent inpatient care in the department of rheumatology of the National Center of Cardiology and Internal Medicine (NCCIM) from 2001 to 2011. Subsequently enrolled patients were followed-up on a regular basis. Study protocol included clinical, instrumental, laboratory and immunological parameters obtained from specially designed registry database of NCCIM (BLIPS 8, ADS-Limathon). All patients fulfilled the revised ACR criteria for SLE. Age, gender, disease activity index (SLEDAI-2K), SLICC Damage Index (SDI) and other parameters obtained at the time of first hospitalization and subsequently in 75 cases out of 107 after 5 years of follow-up observation were included for the statistical analysis. Immunological analysis included determination of anti-dsDNA and anti-Sm antibodies “ANA-LIA-Max 17”. Date and cause of death were determined according to the primary medical records. Results Vast majority of patients (79.4%) enrolled in this study were from the northern part of the country. The study included 91.5% women and 8.4% men with a mean age 30 years and mean disease duration - 2.0 years. It took from 6 months to 3 years since the onset of symptoms to the verification of the diagnosis. Majority of patients (49.5%) were with subacute variant of the disease. Based on disease activity index, patients with moderate and high grade of disease activity were 46.7% and 44%,respectively. Within 5-year follow-up observation of 75 out of 107 patients the remission was achieved in 3.7%, and the low grade disease activity in 6.4% patients. In all cases upon a significant decrease in disease activity, there was a statistically significant increase in SDI score for 1 or higher points. Various irreversible organ damages were found in almost half of the cases (47.6%) at a mean of 2.0 years from the onset of the disease. Majority of patients showed low (28.7%) and moderate (28.3%) SDI score. During observation 27 (36%) of 107 patients died. The main causes of death were active SLE and its complications involving different organ damages: kidney (29.6%), lung (22%) and combined central nerves system (CNS) and kidney (11%). Overall mortality from the concomitant infection was 18.7%, prominently from the infection of the respiratory system, among them 42.7% with severe pneumonia and progressive respiratory failure. Conclusions The study identified that progressive organ damages and infectious complications involving respiratory system were associated with poor prognosis and outcome of patients with SLE in Kyrgyzstan. Disclosure of Interest None declared

Background Due to the smaller size of the molecule and low affinity for platelet factor (f) 4, fondaparinux (F) does not cross react with heparin-induced-thrombocytopenia- antibodies [1]. Also F has some more beneficial mechanisms: reduction of aPl-production (BAFF/Blys) and tissue f expression, C3/C5-inactivation, fXa-C3 cleavage blocking, increase of angiogenic process [2]. This can lead to classify F as pathogenic treatment option for rheumatic diseases (RD) as well as anticoagulant. Objectives To evaluate the affectivity and safety of F in treatment and prevention of thromboses in patients (pts) with RD. Methods The study included 54 pts suffered from the next RD: 8 systemic lupus erythematosus (SLE), 7 rheumatoid arthritis (RA), 4 antiphospholipid syndrome (APS), 25 SLE+APS, 4 systemic sclerosis, 1 osteoarthritis, 2 ANCA-associated vasculitis and 1 Behcet`s disease. All the pts were treated with anticoagulants - 24 pts with F, 25 pts with nadroparin, 1 pts with enoxaparin and 4 pts with rivaroxaban - for different reasons: deep vein thrombosis (DVT), trophic ulcer, thrombotic cerebral microangiopathy, postthrombotic pulmonary hypertension, hypercoagulability due to nephritis, thrombosis prevention in SLE+APS pts with low platelets. Incidences of thrombosis, bleeding events and platelets levels were monitored. 10 pts (RA + vasculitis) had initial high fibrinogen levels. 12 pts with SLE+APS had baseline aPTT elevation from lupus anticoagulant (LA). Direct anti-fXa level monitoring (anti-Xa) was performed. Results All the pts demonstrated clinical improvement. Low anti-Xa was registered in 6 (12%) pts, normal anti-Xa – in 37 (69%) pts and high anti-Xa – in 11 (19%) pts. Pts with low anti-Xa underwent dose correction and none of them had new incidence of thrombosis. Most of pts did not have bleeding complications. Only 1 pt with SLE+APS treated with F developed multiple cutaneous haemorrhages. We discharged F for 24 hours and started again in a half dose. anti-Xa monitoring showed level decrease from 1.73 to 1.3 units/mL. In pts with APS and/or SLE F did not influence on aPL, fibrinogen and aPTT. 3 SLE+APS pts who had distal gangrene and cutaneous necrosis intentionally were treated with high dose of F with anti-Xa ∼2 units/mL. That led to a good clinical response and blood flow recovery in ischemic tissues. There were no any signs and symptoms of bleeding. Conclusions Fondaparinux is an effective and save drug for the treatment and prevention of thrombosis in pts with RD. During the therapy routine coagulation monitoring is not representative because of LA and inflammation. We recommend to monitor signs of bleeding and anti-Xa and to expand its normal rate up to 2 units/mL in pts with distal gangrene and cutaneous necrosis due to SLE and APS. References Smythe MA, Priziola J, Dobesh PP et al. Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism. J Thromb Thrombolysis. 2016 Jan;41(1):165–86. doi: 10.1007/s11239-015-1315-2. Alijotas-Reig J, Ferrer-Oliveras R. Management of refractory obstetric antiphospholipid syndrome: from pathogenesis to novel immunomodulatory therapies. Proceeding of the 9th Meeting of the European Forum on Antiphospholipid Antibodies; 2013 May 16–18; Krakow, Poland. Krakow: Medycyna praktyczna; 2013. Disclosure of Interest None declared

Background Venous thromboembolic events (VTE) such as deep vein thrombosis, thrombophlebitis and thromboembolism of pulmonary artery are an important clinical problem that concerns all spheres of medicine. Patients with chronic inflammatory diseases including RA have an increased risk of venous thromboembolism. It is important to determine risk factors of VTE in patients with RA (standard and associated with disease) for prevention of thrombosis. Objectives To determine prognostic risk factors of venous thromboembolic events in patients with rheumathoid arthritis. Methods 362 patients (F:302, M:61) with definite diagnosis of rheumathoid arthritis were analyzed, 53,7 ± 13,3 years old, duration of disease 12,4 ± 10,9 years. All patients were hospitalized in V.A. Nasonova Reasearch Institute of Rheumatology. Doppler ultrasound of lower limbs veins were done to patients with suspected thrombosis or with thrombosis in past history. Patients were divided in 2 groups: 1st Gr included patients with thrombosis in a moment or in past history – 34/362 (9,9%) and 2nd Gr - patients and without thrombosis – 328/362 (90,1%). Analysis of risk factors was done according to questionnaire survey and medical history. Disease activity was expressed as DAS28 score which is a composite score derived from tender joint count, swollen joint count, ESR and patient9s global assessment of disease activity. Possible prognostic risk factors included age (>40 years, >60years, >75 years), body mass index (BMI) >30, smoking, pregnancy and childbirth, taking antifertility agents, immobilization, surgical treatment, traumas, fractures, diabetes mellitus, pulmonary diseases, cardiac failure, varicose vein disease, cancer, oral and intra-articular ( 5 injections) introduction of glucocorticoids (GCs). In order to identify predictors of venous thromboembolic events we used multivariance analysis (discriminant function classification). Results Multivariance analysis showed that the thrombosis is mainly influenced by following factors: immobilization, cardiac failure, varicose vein disease, oral and intra-articular (>5 injections) introduction of GCs; weighted coefficients: 1,0; 0,92; 3,13; 0,02; 0,52. Function of prediction of thrombosis is suggested: Z =1,0 * immobilization (Yes-1/No-0) + 0,92* cardiac failure (Yes-1/No-0) + 3,13* varicose vein disease (Yes-1/No-0) + 0,02* oral GCs (yes-1/No-0) + 0,52* intra-articular (>5 injections) introduction of GCs (Yes-1/No-0). The value of function Z=1,65 divides patients with and without venous thromboembolic events, sensitivity 64%, specificity 82%, positive predictive relevance 80%. Conclusions Adverse prognostic factors of venous thromboembolic events in patients with rheumathoid arthritis are immobilization, cardiac failure, varicose vein disease, oral and intra-articular (>5 injections) introduction of GCs. Disclosure of Interest None declared

Background Systemic lupus erythematosus (SLE) is a devastating disease affecting different organs, ultimately leading to organ failure and death. To date, there are no data regarding the real-life picture of SLE in Kyrgyzstan. Objectives The goal of the study is evaluation of the quality of life among Kyrgyz cohort of patients with SLE according to the prospective study. Methods 60 patients with definite diagnosis of SLE (ACR, 1997; SLICC, 2012) were treated in the department of rheumatology of NCCIM and observed from 2012 to 2015. They were evaluated by sex, age, disease duration, activity of SLE according the SLEDAI-2K, irreversible organ damage by SLICC Damage Index (SDI), quality of life using the SF-36 questionnaire, LupusQoL, HADS, FACIT, therapy, with monitoring of all parameters every six months for 2 years. From the data of the immunological studies immune linear (immunoblot) “ANA-LIA-Max 17” were analyzed with a purpose of detecting the antibodies of double-stranded DNA, Sm D1 antigen and antibodies of double-stranded DNA-linked immunosorbent analyisis (ELISA), C3-C4 components complement, indirect immunofluorescence of the antinuclear antibody cells of line Hep-2. Results Patients were mainly from the northern region of the republic (81.7%). The vast majority were women (86.7%), with average age 30 years old, with disease duration of about 1.0 years. Dates of illness onset to verify the diagnosis ranged from 1 month to 9 years. The clinical course dominated patients with acute one (47%) and high activity (57%). The clinical symptoms of were cutaneous and articular syndrome (84.2% and 72.3%, respectively), the defeat of the serous membranes (88%) and kidney (68%). Before the treatment, according to the overall SF-36 questionnaire all SLE patients had lower QOL revealed. Marked limitation of life activity of patients was due to the presence of physical and emotional problems with severe anxiety and depression affects on their social functioning. After 2 years significant improvement in quality of life on many scales, except for the scale of mental health is noted. Attention is drawn to the deterioration of quality of life on the scale of “viability”, which characterizes the patient a sense of lack of strength and energy for the period of the disease. The lowest quality of life is reported among Kyrgyz patients in the comparative analysis to QOL of patients with SLE in other 3 countries of Europe (UK, France and Italy) and Russia. Despite the reduction of disease activity (p Conclusions The low quality of life among Kyrgyz cohort of patients with SLE is associated with poor physical, emotional and social functioning. Despite the reduction of disease activity during the treatment, quality of life on the scale of “viability, lack of improvement of mental health component is identified as declining”. Disclosure of Interest None declared

Background In this study, we analyzed incidences of VTE in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) after total knee or hip arthroplasty, compared schemes of drug prevention and evaluated their efficiency. Objectives To evaluate the efficiency of prevention of VTE in patients with rheumatoid arthritis and osteoarthritis after total knee replacement under comparable conditions Methods We studied 151 patients operated in V.A. Nasonova Research Institute of Rheumatology for the period 2014–2015. Of these, 72 patients with RA (47.7%) and 79 patients with OA (52.3%). For a comparative analysis of the efficiency of anticoagulant therapy, each patient group was divided into 2 subgroups by type of drug therapy. The first - nadroparin calcium (the drug therapy was started for 12 hours after the operation at a dose of 0.1 ml per 10 kg of body weight one time per day), the second - nadroparin calcium with transfer to dabigatran etexilate (the first stage of 4 hours after the operation was started therapy by nadroparin calcium, and then after the removal of the epidural catheter moved to the dabigatran etexilate).Doppler ultrasonography (DUS) was routinely performed preoperatively and on postoperative day 7, 14, then 1 time a month for diagnosing a deep venous thrombosis (DVT). Time of observation was 6 months. Results VTE were reported in 6 (3.9%) patients, 1 of them (0.7%) with RA and 5 (3.3%) with OA. Distal deep vein thrombosis developed on 15 days after total knee replacement in RA patient. He received nadroparin calcium only. 4 patients with VTE after surgery from OA group used nadroparin calcium and 1 patient was on combined drug therapy. Of the 6 cases of VTE 4 (66.7%) were asymptomatic and 2 (33.3%) with development of clinical and laboratory picture. The case of thrombosis in a group of RA was asymptomatic. In a perioperative period of clinically significant bleeding was not seen. Conclusions Cases of VTE in patients with RA, despite the large number of risk factors, under comparable conditions is significantly lower than patients with OA. The number of asymptomatic deep vein thrombosis prevails over the development of clinical and laboratory complex of symptoms in both groups. In patients with RA and OA who were from the first group have reported 5 cases of VTE and only 1 case of VTE have reported in patients who were from second group. Combined drug VTE prevention in patients with RA and OA has been most effective and safe. Disclosure of Interest None declared

Background Antiphospholipid antibodies (aPL) are included in diagnostic criteria of antiphospholipid syndrome (APS) as good as systemic lupus erythematosus (SLE). There are a few cases of SLE onset in patients with isolated APS and vice versa development of APS in lupus patients in several years. Objectives To analyze the mutual clinical and serologic features of APS and SLE, to determine the number of patients going on to develop other autoimmune disease after long-term follow-up and to define risk factors of “transformation” from APS to SLE or lupus onset in APS patients. Methods The study included 314 unselected patients (141 with SLE, 98 with SLE+APS and 75 with “primary” APS (PAPS)) who had admitted to the department of systemic connective tissue diseases of Nasonova Scientific Research Institute of Rheumatology (Moscow, Russia) between June 2004 and September 2012. Patients fulfilled the 1997 ACR classification criteria for SLE and the Sapporo International Criteria of APS respectively. After staying in the hospital 195/314 (62%) patients continued to attend the Institute outpatiently. We excluded 64 patients with both SLE and APS, and the final study group was composed of 131 patients (83 SLE and 48 PAPS) with a mean age 36.4±12 years and mean follow-up 7±3 years (from 3 to 11)). Thromboses were registered in all patients with PAPS and in 1 (1%) patient with SLE (without aPL). Immunologic disorders included high and mild positive anticardiolipin antibodies (in 10% SLE and 100% PAPS), anti-beta-2-glicoprotein-1 antibodies (in Results The main mutual manifestations were livedo reticularis (in 12% SLE and 64% PAPS) and sick headache (in 14% SLE and 35% PAPS). The other mutual features were seen with the next prevalence: hemolytic Coomb9s positive anemia (in 24% SLE and 12% PAPS), thrombocytopenia (in 11% SLE and 19% PAPS), heart valve disease (in 9% SLE and 43% PAPS), recurrent fetal losses (in 8% SLE and 38% PAPS), Raynaud9s phenomenon (in 38% SLE and 7% PAPS), cutaneous ulcers (in 3% SLE and 22% PAPS), avascular bone necroses (in 25% SLE and Conclusions SLE and APS have several mutual manifestations and can run into each other. Positive aPL and livedo reticularis are risk factors for development of “secondary” APS in lupus patients. Recurrent fetal losses can be possible factors related to the joining of SLE to APS. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) patients present an increased risk of venous thromboembolism (VT), an important cause of morbidity and mortality. An increased risk of VT events (VTE) may negatively influence the prognosis and clinical outcomes in RA pts. Therefore it is important to identify risk factors in RA pts (standard and associated with the disease) for prevention of VTE. Objectives To determine prognostic risk factors for VTE in RA patients. Methods 187 patients (F:152, M:35) with confirmed RA were analyzed, 53,8±12,8 y.o, duration of the disease 12,2±10,8 y. All patients were hospitalized in V.A. Nasonova Research Institute of Rheumatology. Patients were grouped in 2 arms: 27/187 (14,4%) pts with VTE on enrollment or with history of prior ETV; and 160/187 (85,6%) pts without prior ETV. Existing ETV risk factors were evaluated based on questionnaire survey data. Disease activity was expressed as DAS28 score which is a composite score derived from tender joint count, swollen joint count, ESR and patient9s global assessment of disease activity. Possible prognostic risk factors included age (women>55 years, men>65years), BMI, smoking, cardiovascular diseases, traumas, fractures, immobilization, pregnancy and childbirth, intake of contraceptives, diabetes mellitus (DM), intra-articular administration of glucocorticoids (GCs), cancer, duration and activity of RA. RA activity and duration were assesses using contingency table and the χ2 test. Multivariate analysis (discriminant function classification) was used to identify other predictors of VTE. Results Analysis of contingency table with the χ2 test showed a statically significant difference in VTE rates between the two groups – patients with high disease activity (Group 1, n=55) and patients with remission, low and moderate RA activity (Group 2, n=119). In Group 1 there were 16/55 (29,09%) pts with VTE and in Group 2 - 11/119 (9,24%), p Z =1,728 * hypertension (Yes-1/No-0) + 1.119 * heart failure (Yes-1/No-0) + 1.012 * immobilization (Yes-1/No-0) + 0.61 * pregnancy and childbirth (yes-1/No-0) + 1.424 * DM (Yes-1/No-0) + 0.643 * intra-articular GCs (Yes-1/No-0). The threshold value of Z=2,632 allows to predict VTE events in RA pts with 70% sensitivity, 70% specificity and 70%positive predictive relevance. Conclusions Adverse prognostic factors for VTE development in RA patients are disease activity, hypertension, heart failure, immobilization, pregnancy and childbirth, diabetes mellitus, and intra-articular administration of glucocorticoids. Disclosure of Interest None declared

Background Deep vein thrombosis (DVT) of the lower limbs during operations knee and hip arthroplasty in patients with rheumatic diseases are observed in 7-27% cases. Objectives To evaluate the efficiency of prevention of DVT in patients with rheumatic diseases and osteoarthritis under comparable conditions. Methods We have analyzed 304 patients operated in for the period 2012-2013. Of these, 188 - with rheumatic diseases, 116 patients - with osteoarthritis. A distinctive feature of the patients with rheumatic diseases was the presence of concomitant drug therapy for the underlying disease. Thus, 176 (94%) of patients with rheumatic diseases received NSAIDs, 168 (89%) of patients received disease-modifying antirheumatic drugs (DMARDs), 81 (43%) of patients received glucocorticosteroids, 45 (24) % of patients received biologic DMARDs. These drugs indirectly affect the hemostatic system, increase the effect of each other and inhibit platelet hemostasis. In the preoperative period the incidence of DUS-confirmed DVT was in 12 patients (6.4%) with rheumatic diseases, most of which consisted of patients with systemic lupus erythematosus (SLE) and SLE + anti-phospholipid syndrome (APS) - 7 patients (3,7%) and the incidence of DUS-confirmed DVT was in 15 patients (12.9%). It was old thrombosis usually under vessel recanalization. Patients with post-thrombotic venous disease of the lower extremities for 7 days prior to surgery taken nadroparin or fondaparinux sodium, on the 2nd day after surgery patients was transferred to oral anticoagulants. Another patients (292) with rheumatic diseases and osteoarthritis without DVT in anamnesis received oral anticoagulants – a direct thrombin inhibitor - Dabigatran etexilate (174 patients) and rivaroxaban (118 patients). The first intake of dabigatran etexilate (110mg) or rivaroxaban (10mg) was performed on the first day after the surgery. Later the patients were taking 220 mg (2 capsules) of dabigatran etexilate once per day or 10 mg of rivaroxaban once per day for 28-35 days. Doppler ultrasonography (DUS) was routinely performed preoperatively and on postoperative day 3, 7, 14, then 1 time a month for diagnosing a deep venous thrombosis (DVT). Time of observation was 3 months. Results None of the patients with rheumatic diseases after knee or hip replacement in the early postoperative period deep vein thrombosis of the lower limbs were found. In the control group of patients with osteoarthritis in the early postoperative period identified 8 cases (6.9%) deep vein thrombosis of the lower limbs. The causes of thrombosis were unjustified self- removal of the drug for 15-20 days after surgery (6 cases), and later appointment of the anticoagulant (2 cases). In the perioperative period of clinically significant bleeding was not seen. Conclusions Application of the above prevention of deep vein thrombosis of the lower limbs has been effective and convenient in the early postoperative period in patients with rheumatic diseases in replacement of hip or knee joints, but requires further study in patients with osteoarthritis. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4909

Background Deep venous thrombosis of the lower limbs occur in 42-65% of the total knee and total hip arthroplasty. Objectives To evaluate the efficiency of oral anticoagulants in the post operational period for patients with rheumatic diseases. Methods We have analyzed 146 patients with rheumatic diseases affections of the knees and hips who were operated in the Department of Traumatology and Orthopaedics of the State Institute Of Rheumatology Of Russian Academy Of Medical Sciences in 2012. We have performed thromboembolic compications of 48 patients with oral anticoagulants – a direct thrombin inhibitor - Dabigatran etexilate. We have used a Xa inhibitor factor on 98 patients – a rivaroxaban. The first intake of dabigatran etexilate (110mg) or rivaroxaban (10mg) was performed on the first day after the surgery. Later the patients were taking 220 mg (2 capsules) of dabigatran etexilate once per day or 10 mg of rivaroxaban once per day for 28-35 days. We were taking the control on the efficiency of thromboembolic complications with the help of ultrasound triplex angioscanning. The first ultrasound scanning was taken on the 3 day after the surgery and then on a weekly basis. Results Venous thromboses of the lower limbs were not found in 45 cases (93.8% of the patients) who were taking dabigatran etexilate during weekly ultrasound scanning. Early unjustified cancellation of dabigatran etexilate after 15 days after the total hip replacement (outpatient) in case of three patients (6.2%) led to the floating ileofemoral thrombosis. One patient (1.02%) who was taking rivaroxaban had occlusive thrombosis of the femoral vein on the contralateral side. Reason: late intake (start after 3 days) of the prescribed medicine. Bleedings were not noted in postoperative period. Conclusions Dabigatran etexilate and rivaroxaban were effective and convenient medicines for the thromboembolic complications prevention for patients in rheumatic diseases in the postoperative period. Disclosure of Interest None Declared

Article abstract Antiprothrombin antibodies (aPT), a new serologic marker of antiphospholipid syndrome, were studied in 46 patients randomly selected from 73 with Sneddon’s syndrome and 20 matched normal controls. aPT were elevated in 26 patients (57%) and were not found in any of the controls. The addition of aPT data increased the proportion of Sneddon’s syndrome patients with at least one type of antiphospholipid syndrome marker from 65 to 78%. The finding that aPT are common in Sneddon’s syndrome supports the hypothesis that Sneddon’s syndrome is a form of antiphospholipid syndrome.