Стратегия лечения системной красной волчанки «до достижения цели» (Treat-to-Target SLE). Pекомендации международной рабочей группы и комментарии российских экспертов Соловьев С.К., Асеева Е.А., Попкова Т.В., Клюквина Н.Г., Решетняк Т.М., Лисицына Т.А., Кошелева Н.М., Цанян М.Э., Меснянкина А.А., Панафидина Т.А., Кондратьева Л.В., Середавкина Н.В., Герасимова E.В.Начало нового тысячелетия ознаменовано существенным прогрессом в развитии ревматологии: более глубо-ко изучен патогенез многих ревматических заболеваний (РЗ), валидированы критерии диагностики, разра-ботаны индексы активности, внедрены понятия ремиссии и обострения, большое внимание стало уделяться изучению качества жизни пациентов. Существенно расширена возможность фармакотерапии иммуновоспа-лительных РЗ за счет появления генно-инженерных биологических препаратов (ГИБП). Изменилась и стра-тегия терапии пациентов с РЗ. В 2010 г. выдвигается концепция «Лечение до достижения цели» (Treat to Target) для ревматоидного артрита, а позднее для анкилозирующего спондилита. В январе 2013 г. по инициа-тиве ведущих мировых ревматологов стартовал проект создания концепции «Лечение до достижения цели» для системной красной волчанки (СКВ). Результатом их работы стали опубликованные в 2014 г. рекоменда-ции «Лечение СКВ до достижения цели», сформулированные в виде 4 основополагающих принципов и 11 основных рекомендаций. Цель данной публикации -общая характеристика основных положений принципов и рекомендаций с комментариями ведущих специалистов-люпологов с учетом особенностей СКВ в Российской Федерации и обсуждением некоторых дискуссионных и нерешенных проблем. Ключевые слова: системная красная волчанка; «Лечение до достижения цели»; мониторинг. Для ссылки: Соловьев СК, Асеева ЕА, Попкова ТВ и др. Стратегия лечения системной красной волчанки «до достижения цели» (Treat-to-Target SLE). Pекомендации международной рабочей группы и комментарии рос-сийских экспертов. Научно-практическая ревматология. 2015;53(1):9-16. The start of the new millennium is marked by a substantial progress in the development of rheumatology: pathogenesis of many rheumatic diseases (RDs) was more deeply studied; their diagnostic criteria validated; disease activity indices worked out; the concepts of remission and exacerbation introduced; much attention has been given to the investigations of quality of life in patients. The possibility of pharmacotherapy for immunoinflammatory RDs was extended by the advent of biological agents (BA). The treatment strategy for RDs was also changed. The treat-to-target concept was put forth for rheumatoid arthritis in 2010 and for ankylosing spondylitis later. The project of treat-to-target concept in systemic lupus erythematous (SLE) was launched on the initiative of the world's leading rheumatologists in January 2013. The result of their work is the treat-to-target-in-SLE recommendations published in 2014 and formulated as 4 basic principles and 11 general recommendations. The purpose of this publication is to provide general characteristics of the basic provisions...

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BackgroundOur aim was to compare serum levels of cytokines in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).ObjectivesComparative data on cytokine profile in SLE and rheumatoid arthritis RA patients are scarce.MethodsWe examined serum samples from 80 pts with SLE, median and interquartile range (25th–75th percentile) of disease duration 48 (2–432) months; age 31,5 (16–65) years; 72 female; 74 pts with RA, disease duration 90,0 (30,00–192,0) months; age 54,0 (44,0–62,0) years; 59 female, and 28 healthy donors. Cytokine analyses were performed with Bio-Plex® technology (Human Grp I Cytokine 27-plex panel).ResultsPts with SLE had significantly lower levels of IL-1β, -1ra, -2, -9, eotaxin, G-CSF, IFN-γ, MIP-1β, TNF-α, VEGF and higher levels of IL-4, -6, -8, -12, GM-CSF, MCP-1, PDGF-BB, RANTES than healthy donors. Compared to RA, cytokine/chemokine levels from SLE were significantly different. The concentrations of IL-1β, -1ra, -2, -5, -6, -7, -9, -10, -13, 15, eotaxin, FGF, G-CSF, IFN-γ, IP-10, MIP-1α, TNF-α, VEGF in SLE were significantly lower than RA. The concentrations of IL-4, -8, MCP-1, MIP-1β, PDGF-BB, RANTES was higher in the SLE cohort (Table 1).ConclusionsSerum concentration of most proinflammatory, Th-2 related, bone marrow–derived cytokines, stromal cells and angiogenic factors in SLE pts is substantially lower than in healthy donors and pts witch RA. These data demonstrate significantly higher chemokine levels in SLE versus RA.ReferencesChun HY, Chung JW, Kim HA, Yun JM, Jeon JY, Ye YM, Kim SH, Park HS, Suh CH. Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol. 2007; 27(5):461–6.Kokkonen H, Söderström I, Rocklöv J, Hallmans G, Lejon K, Rantapää Dahlqvist S. Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis. Arthritis Rheum. 2010; 62(2):383–91. doi: 10.1002/art.27186.Sieber J, Daridon C, Fleischer SJ, Fleischer V, Hiepe F, Alexander T, Heine G, Burmester GR, Fillatreau S, Dörner T. Active systemic lupus erythematosus is associated with a reduced cytokine production by B cells in response to TLR9 stimulation. Arthritis Res Ther. 2014;16(6):477. doi: 10.1186/s13075-014-0477-1.Disclosure of InterestNone declared

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Objective: to study the frequency of hyperleptinemia in patients with systemic lupus erythematosus (SLE), its relationship with clinical and laboratory manifestations of the disease, drug therapy, and other metabolic disorders.Patients and methods. The cross-sectional study included 46 women with a definite diagnosis of SLE (median age 40 [31; 48] years) and disease duration 3.0 [0.9; 9.0] years. Glucocorticoids (GC) were received by 38 (83%) patients, hydroxychloroquine – by 35 (76%), immunosuppressants – by 10 (22%), biologic disease-modifying antirheumatic drugs – by 5 (11%). In all patients, fasting levels of glucose, leptin, apoliproprotein B (ApoB) and immunoreactive insulin were determined, and homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. Concentration of leptin ≥11.1 ng/ml, ApoB – >1.6 mg/ml were considered an elevated level. HOMA-IR index ≥2.77 corresponded to the presence of insulin resistance (IR).Results and discussion. Hyperleptinemia was found in 34 (74%) patients with SLE, an increased level of ApoB – in 19 (41%), IR – in 10 (22%). In patients with hyperleptinemia, serositis, positivity for anti-double-stranded DNA (aDNA) and hypocomplementemia were less common, overweight and obesity were more frequent, the SLEDAI-2K index was lower, the aDNA level was lower, and the concentration of the C3 component of complement, insulin, HOMA-IR index, body mass index (BMI) and disease duration were higher (p<0.05 for all cases). BMI <25 kg / m2 had 26 (57%) women, 14 (54%) of whom had hyperleptinemia. In patients with BMI <25 kg / m2, we found a relationship between leptin concentration and disease duration (r=0.4, p=0.04), SLE activity according to SLEDAI-2K (r=-0.6, p=0.003), levels of aDNA (r=-0.6, p<0.001), C3 component of complement (r=0.5, p=0.01), maximum (r=0.7, p<0.001) and supporting (r=0,5, p=0.023) GC doses.In patients with BMI ≥25 kg/m2 (n=20), no such relationship was observed.Conclusion. Hyperleptinemia was found in the majority of women with SLE; elevated levels of ApoB and IR were much less common. Patients with hyperleptinemia are characterized by a longer duration and less activity of the disease, as well as the presence of overweight and obesity and an increase in the HOMA-IR index. In SLE patients with normal body weight, the concentration of leptin increased along with GC dose elevation.

О р и г и н а л ь н ы е и с с л е д о в а н и я ФГБНУ «Научноисследовательский институт ревматологии им. В.А. Насоновой»,

BackgroundAutoantibodies against intracellular antigens are a serological hallmark of ANA-associated systemic autoimmune rheumatic diseases (AARD) such as SLE. IIF on HEp-2 cells for ANA remains the “gold standard” but it has very low positive predictive value. Up to 20% of serum samples from HI have been reported to have a positive ANA IIF test, the majority of them due to the presence of anti-dense fine speckled 70 (anti-DFS70) antibodies. Monospecific anti-DFS70 antibodies represent a biomarker that can be used to discriminate AARD patients (pts) from HI in ANA IIF positive subjects. Recognition of the DFS70 ANA IIF pattern can be challenging. The DFS-KO Hep-2 cells inhibit anti-DFS70 antibodies reactions, providing clear differentiation of the DFS pattern from classical ANA patterns.ObjectivesTo evaluate the utility of a novel HEp-2/DFS70-KO IIF substrate for the detection of anti-DFS70 antibodies in HI and SLE pts.MethodsWe studied 45 HI (36 F/9 M; age 50.4 [24.0–72.0] years, median [interquartile range 25–75%]) and 12 pts with SLE (ACR criteria, 1997) (10 F/2M, age 38.9 [17.0–65.0] years; disease duration 100.3 [4.0–432.0] months; SLEDAI 2K score 11.7 [2–30]; SLICC damage index score 1.28 [0–4]). Serum samples were tested for classical ANA and anti-DFS70 antibodies by IIF technique with a mixture of standard HEp-2 cells and DFS70-KO HEp-2 cells (“Trinity Biotech”, Bray, Ireland) as a substrate. Fluorescence titers ≥1: 160 were considered as positive for ANA patterns.ResultsANA were present in 7/45 (15.6%) of HI and in 12/12 (100%) of SLE pts. All SLE pts and 3/45 (6.7%) of HI showed classic ANA patterns (homogeneous, speckled, and mixed) in the absence of DFS70 pattern. 4/45 (8.9%) of HI had classic ANA negative/anti-DFS70 antibodies positive IIF results. Isolated anti-DFS70 antibodies were found in 57% of ANA IIF positive HI. Among HI classic ANA and anti-DFS70 antibodies were detected in the low- to medium-titer range (1:160–1:320). The frequency of anti-DFS70 antibodies did not correlated with age.ConclusionsThe detection of isolated anti-DFS70 antibodies may be regarded as an exclusion criterion for the diagnosis of SLE. The testing for anti-DFS70 antibodies in a single step by HEp-2/DFS70-KO IIF method should be included into a modified ANA diagnostic algorithm. Additional investigations are required to evaluate the clinical relevance of anti-DFS70 autoantibodies.Disclosure of InterestNone declared

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease of unknown etiology, characterized by overproduction of organ-nonspecific autoantibodies to various components of the cell nucleus and cytoplasm and the development of immune-inflammatory damage to internal organs. The debut of SLE is preceded by an asymptomatic period, characterized by impaired immunological tolerance to its own autoantigens, determined by the multifaceted interaction of external, genetic and epigenetic factors, hormonal disorders, microbiome pathology, stress effects, etc. Development of a certain spectrum of clinical symptoms characteristic of SLE along with the detection of a reflects the progression of the immunopathological process in SLE, however, there is no generally accepted term that defines the patient’s condition, which has individual serological and clinical signs characteristic of this disease. In rheumatology, the concept of «incomplete» SLE is currently most often used. The problems of early diagnosis of SLE, clinical and laboratory predictors of the transformation of “incomplete” SLE into “reliable” SLE, difficulties in diagnosing SLE during the COVID-19 pandemic are considered. Particular attention is paid to the comparative characteristics of the immunopathological mechanisms of SLE and COVID-19.