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BackgroundTakayasu arteritis (TAK) is a granulomatous vasculitis that involves aorta and/or its main branches and usually affects young or middle-aged women (before 50 years of age). Tocilizumab (TOCI) (monoclonal antibodies to IL-6 receptor) is a promising agent for treatment of refractory TAK, also clinical experience is very limited.ObjectivesTo evaluate the efficacy and safety of short-term treatment with TOCI in patients with TAK refractory to standard immunosuppressive treatment.MethodsWe enrolled in our case series all patients with TAK who were treated with TOCI. Diagnosis of TAK was established according to the ACR criteria and CHCC2012. TOCI was administered intravenously at a dosage of 8 mg/kg every 4 weeks. Criteria of efficacy included complete and incomplete remission and relapse of arteritis. Activity of disease was evaluated using the NIH criteria. In all patients, we calculated the Indian Takayasu Clinical Activity Score (ITAS2010).ResultsTen patients with TAK (all females, median age 23.5 years (19-56), type 5 (generalized) in nine patients) were included in retrospective study. Median duration of disease was 48.5 months (29-146). High activity of disease was confirmed by standard laboratory tests (median ESR 56 mm/h, CRP 15.4 mg/L) and MRA/PET/US. Median ITAS score was 5 (3-12), median Kerr index was 2 (1-4). Prior to tocilizumab administration all patients were treated with combination of immunosuppressive drugs (PRED + MTX or MMF or TNF inhibitors (n=3)) for 41 months (16-140).Average duration of TOCI treatment was 6 months (3-15). Complete and partial remission was achieved in 4 (40%) and 3 (30%) patients, respectively. Median PRED dose was reduced from 30 mg (10-60) to 9.5 mg daily (≤10 mg daily in 5 patients). In 3 patients we observed carotodynias and PRED dose was increased to 10-20 mg. After treatment average ESR and CRP were 12 mm/h and 0.8 mg/L, respectively. Repeated MRA and US confirmed low activity of disease in 5 (71.4%) of 7 patients while in 2 patients (28.6%) MRA showed persistent active vascular inflammation. Median ITAS score declined to 1 (1-5) and median Kerr index to 0 (0-2). TOCI infusions were well-tolerated; we observed 3 cases of carotodynia in few days after infusions; 2 patients developed community-acquired pneumonia and 1 – Herpes zoster infection and purulent bronchitis, with subsequent TOCI dose reduction to 4 mg/kg. In 2 patients surgical vascular intervention was performed (before treatment it was impossible due to active vasculitis). Two patients developed relapse of arteritis when we attempted to increase the dosing interval of TOCI to 6–8 weeks.ConclusionsTOCI is effective in case of active systemic inflammation in patients with refractory TAK. The risk of infections should be taken into account. We observed high rate of carotodynias after TOCI infusions, that requires further confirmation. Long-term results with clinically important end-points (vascular interventions, risk of stenosis progression, long-term outcomes etc.) are awaited.Disclosure of InterestNon...

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О р и г и н а л ь н ы е и с с л е д о в а н и я 1 Национальный Центр кардиологии и терапии (НЦКТ) им. академика М. Миррахимова, Бишкек, Кыргызская Республика; 2 ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»,

Objective: to study clinical presentation, course variants and complications of Takayasu arteritis (AT) in Kyrgyz patients.Patients and methods. 75 Kyrgyz patients with a definite diagnosis of AT were included in the study, most of them were women (93.3%). The median age was 33 [23; 40] years, the median duration of the disease was 7 [3.0; 13.0] years. The anatomical type of vascular lesions was determined using the angiographic classification of R. Moriwaki et al., the AT activity – according to the BVAS index, the clinical stage of AT – using the R. Jefferson classification, the severity and prognosis of the disease – according to the K. Ishikawa classification. Highly sensitivity CRP (hsCRP) was assessed in 44 (58.67%) patients, interleukin 6 (IL6) – in 26 (34.7%). Instrumental procedures included duplex Doppler ultrasonography of peripheral arteries and contrast-enhanced computed pan aortography.Results and discussion. The mean age of AT onset was 24.4±9.4 years. The majority of patients had V anatomical type of vascular lesions (61.3%), vascular stage (89.3%), severe stenosis (54.7%) with predominant affection of the brachiocephalic trunk (68%), common carotid arteries (53.7 %) and renal (52%) arteries. Most patients (82.7%) at the time of inclusion in the study had a severe exacerbation of AT according to the BVAS index. An increase in hsCRP level was seen in 66% of cases, IL6 – in 31%. At the onset of AT, 20% of patients had fever, general weakness, weight loss, myalgia and/or arthralgia. 43% of patients had ≥2 complications. The clinical manifestations of AT were mainly characterized by cardiovascular pathology (77.3%) with the formation of relative aortic valve insufficiency (AVI) (93.1%) and kidney damage (57.3%) with the development of renovascular arterial hypertension (91%). At the first visit, more than one third of patients (37.3%) had irreversible damage, accompanied in half of them by AVI degree II or III.Conclusion. Young women predominated among Kyrgyz patients with AT. Most of the patients had anatomical type V AT (61.3%), vascular stage (89.3%), severe stenosis (54.7%), affection of the brachiocephalic trunk (68%), common carotid (57.3%) and renal (52%) arteries. Severe exacerbation of the disease was observed in 82.7% of patients. The presence of ≥2 complications worsened the prognosis of AT. The clinical manifestations of AT were characterized mainly by cardiovascular pathology (77.3%) and kidney damage (57.3%). In more than one third of patients (37.3%) AT was diagnosed late.

The development of irreversible organ damage (IOD) in systemic lupus erythematosus (SLE) significantly increases the risk of death, worsens the quality of life and significantly increases the cost of treatment. The development and implementation of specific tools that will promote early identification of the risk of unfavorable outcomes is a priority. The article presents literature review on a new method for prediction of unfavorable outcomes in SLE – frailty index (FI, vulnerability index). FI, developed by a group of international experts on the basis of the database of the international cohort of SLE patients – SLICC (Systemic Lupus International Collaborating Clinics) – is easily reproducible in real clinical practice and can be used in patients with an early stage of SLE to predict the risk of death, the development of IOD. and hospitalization. The SLE Forecasting index of unfavorable outcomes (SLICC-FI) appears to be a promising clinical and research tool for identifying those who need more careful monitoring and an individual therapeutic strategy at an early stage of the disease.

systemic lupus erythematosus (SLE) largely depends on migration of pulmonary artery smooth muscle cells (PASMCs). In this study, we tested whether IgG from SLE with PAH have stimulatory effects on PASMC migration. Methods Sera from 6 SLE patients, including 1 with PAH, and 7 healthy subjects were collected, and IgG was purified using protein A or protein G. PASMC migration was examined by a Boyden chamber method. Lamellipodia formation and antibody binding sites in the cells were examined by immunocytochemistry. Identification of anti-enolase1 antibodies was performed by immunoprecipitation, western blotting, mass spectrometry, and ELISA. Results IgG from SLE with PAH significantly increased migration of PASMCs than those without PAH in a concentration dependent manner (p<0.001). After incubation with IgG, the number of cells with lamellipodia, which represents rearrangement of the cytoskeleton necessary to migration, was 1.4-fold higher in SLE with PAH than those without PAH (p<0.01). In immunocytochemistry, IgG from SLE with PAH were colocalized with b-tubulin in the cytoplasm of PASMCs, and western blotting showed that the antibodies bound to a~50 kD protein in the lysates, which was subsequently identified as enolase1 reported to be involved in cell migration. Furthermore, the titer of IgG anti-enolase1 antibodies was 1.5-fold higher in SLE patients with PAH than those without PAH. Conclusions IgG from a patient with SLE accompanied by PAH promoted a migration of PASMCs, which is possibly ascribed to autoantibodies to enolase1.

The efficiency of glucocorticoid (GC) therapy for systemic lupus erythematosus (SLE) is beyond question and is confirmed by the experience gained over many decades of their use. However, there are many problems with prolonged GC use, even in its low and medium doses. In particular, the development of GC-associated irreversible organ damages significantly worsens prognosis and causes a decrease in quality of life and social adaptation and a substantial increase in treatment costs. On the other hand, the current capabilities of early diagnosis, pathogenetic therapy, and monitoring in many patients with SLE allow for maintaining low disease activity and remission, the conditions in which the feasibility of further GC treatment can and should be decided. The paper gives the data available in the literature and the authors’ own studies on the possibility and prospects of GC withdrawal in SLE patients in a stage of low disease activity and remission.