Нейтрофилы – это клетки врожденной иммунной системы, которые длительное время рассматривались только как первая линия защиты организма от чужеродных веществ. С открытием способности нейтрофилов к образованию внеклеточных ловушек (англ. neutrophil extracellular traps, NETs) в процессе нетоза (формирования NETs) расширилось представление о вкладе нейтрофилов в развитие патологии человека. В настоящее время гиперактивация нейтрофилов с повышенным высвобождением NETs рассматривается как важный механизм в патогенезе многих воспалительных, аутоиммунных заболеваний, а также тромбозов. Болезнь Бехчета и антифосфолипидный синдром (АФС) – модели хронической тромбовоспалительной патологии. В обзоре представлены современные представления о вкладе нетоза в развитие гиперкоагуляции, тромбозов при болезни Бехчета и АФС. Neutrophils are the cells of the innate immune system, which were for a long time considered only as the first line defense against allogeneic substances. The idea of neutrophils contribution to human pathology expanded with the discovery of neutrophils ability to form neutrophil extracellular traps (NETs) during NETosis (NETs formation). Neutrophil hyperactivation with increased NETs release is now considered an important mechanism in the pathogenesis of multiple inflammatory and autoimmune diseases, as well as thrombosis. Behcet’s disease and antiphospholipid syndrome (APS) are the models of chronic thromboinflammation. The review presents current views on NETosis contribution to hypercoagulability, as well as thrombosis in Behcet’s disease and APS.

Введение. Антифосфолипидные антитела (аФЛ) — гетерогенная группа аутоантител, гиперпродукция которых приводит к симптомокомплексу, именуемому антифосфолипидным синдромом (АФС). Семейство аФЛ включает в себя большую группу аутоантител, к классическим серологическим маркерам относят волчаночный антикоагулянт (ВА), антитела к кардиолипину (аКЛ) IgG/IgM изотипов и антитела к β2‑гликопротеину 1 (анти-β2-ГП1) IgG/IgM изотипов. Роль IgA изотипа аКЛ и анти-β2-ГП1 продолжает обсуждаться как при АФС, так и при системной красной волчанке (СКВ). Цель исследования: определить роль IgА аКЛ и IgA анти-β2-ГП1 в развитии сосудистых осложнений у пациентов с АФС и СКВ. Материалы и методы. В проспективное обсервационное исследование были включены 187 пациентов, наблюдавшихся в ФГБНУ НИИР им. В.А. Насоновой в период с 2019 по 2021 гг. с одним из следующих диагнозов: первичный АФС (ПАФС), вероятный АФС, СКВ с АФС, СКВ без АФС. Группу сравнения составили 49 пациентов, среди них 40 пациентов были с другими ревматическими заболеваниями (РЗ), 3 беременные женщины без РЗ и 6 пациентов с тромбозами в анамнезе без установленной причины. В контрольную группу вошли 100 относительно здоровых лиц (без РЗ, не имеющих онкологической патологии и инфекционных заболеваний). Исследование аФЛ включало определение IgG/IgM аКЛ, IgG/IgM анти-β2-ГП1 методом иммуноферментного анализа, IgG/IgM/IgA аКЛ, IgG/IgM/IgA анти-β2-ГП1 методом хемилюминесцентного анализа, ВА. Были определены уровни позитивности в хемилюминесцентных единицах (CU): для IgG аКЛ ( > 25,9 CU), для IgM аКЛ ( > 19,5 CU), для IgA аКЛ ( > 18,9 CU), для IgG анти-β2-ГП1 ( > 32,0 CU), для IgМ анти-β2-ГП1 ( > 6,9 CU), для IgА анти-β2-ГП1 ( > 20,0 CU). Результаты. Частота встречаемости IgA аКЛ и IgA анти-β2-ГП1, а также их уровни были статистически значимо выше у пациентов с АФС (первичным АФС и СКВ + АФС) по сравнению с их уровнями у больных СКВ, в группах сравнения и контроля (р < 0,05). IgA аКЛ и IgA анти-β2-ГП1 достоверно ассоциировались с тромбозами при АФС (χ2 = 4,96; р = 0,02 и χ2 = 4,37; р = 0,04 соответственно). Риск развития тромбоза у пациентов с позитивными IgA аКЛ был в 2,04 раза выше и при позитивных значениях IgA анти-β2-ГП1 — в 2 раза выше по сравнению с пациентами без антител. Прослежена значимая взаимосвязь IgA анти-β2-ГП1 с артериальными тромбозами (χ2 = 4,67; р = 0,03), вероятность которых в 2,04 раза выше у пациентов с наличием IgA анти-β2-ГП1. Верификация достоверного АФС статистически значимо ассоциировалась с позитивностью IgA аКЛ (χ2 = 23,96; р < 0,0001) и IgA анти-β2-ГП1 (χ2 = 15,00; р < 0,0001). Выявлена высокая специфичность IgA аКЛ и IgA анти-β2-ГП1 в отношении как диагноза АФС, так и его клинических проявлений, несмотря на низкую чувствительность. IgA аФЛ определяли существенно чаще у пациентов на фоне позитивности IgG/IgM аКЛ и IgG/IgM анти-β2-ГП1. Уровни IgA аКЛ и IgA анти-β2-ГП1 значимо коррелировали с IgG/IgM аКЛ, IgG/IgM анти-β2-ГП1, в большей степени с IgG аФЛ. Изолированной позитивности IgA аКЛ и IgA анти-β2-ГП1 не установлено. Заключение. Выявлена взаимосвязь тромбозов и АФС с IgA аКЛ и IgA анти-β2-ГП1. Отмечена высокая специфичность IgA аКЛ и IgA анти-β2-ГП1 (95 и 93% соответственно) в отношении диагноза АФС при низкой чувствительности (54 и 44% соответственно). Изолированной позитивности IgА аФЛ не установлено. Introduction. Antiphospholipid antibodies (aPL) are a heterogeneous group of autoantibodies whose overexpression leads to a symptom complex called antiphospholipid syndrome (APS). The aPL family is a large group of autoantibodies; classical serological markers include lupus anticoagulant (LA), IgG/IgM anti-cardiolipin antibodies (aCL), and IgG/IgM anti-β2‑glycoprotein 1 antibodies (anti-β2-GP1). The role of IgA aCL and anti-β2-GP1 is being discussed in both APS and systemic lupus erythematosus (SLE). Objective: to determine the role of IgA aCL and IgA anti-β2-GP1 in the development of vascular complications in patients with APS and SLE. Materials and Methods. A prospective observational study enrolled 187 patients who were followed up at Nasonova Research Institute of Rheumatology in 2019–2021 with one of the following diagnoses: primary APS (PAPS), probable APS, SLE with APS, and SLE without APS. A comparison group included 49 patients: 40 patients with other rheumatic diseases (RDs), 3 pregnant healthy individuals (without RDs, cancer or infectious diseases). The aPL study determined IgG/IgM aCL and IgG/IgM anti-β2-GP1 by ELISA, IgG/IgM/IgA aCL and IgG/IgM/IgA anti-β2-GP1 by chemiluminescent assay, LA. The positivity levels were determined in chemiluminescent units (CU): for IgG aCL ( > 25.9 CU), for IgM aCL ( > 19.5 CU), for IgA aCL ( > 18.9 CU), for IgG anti-β2-GP1 ( > 32.0 CU), for IgM anti-β2-GP1 ( > 6.9 CU), for IgA anti-β2-GP1 ( > 20.0 CU). Results. The incidence of IgA aCL and IgA anti-β2-GP1, as well as their level, were statistically significantly higher in patients with APS (primary APS and SLE + APS) compared with the corresponding level in SLE patients, in the comparison and control groups (p < 0.05). IgA aCL and IgA anti-β2-GP1 were significantly associated with thromboses in APS (χ2 = 4.96; р = 0.02 and χ2 = 4.37; р = 0.04, respectively). Thrombosis risk in patients with positive IgA aCL was 2.04 times higher and with positive IgA anti-β2-GP1 — 2 times higher compared to that in patients without antibodies. There was a significant relationship between IgA anti-β2-GP1 and arterial thrombosis (χ2 = 4.67; р = 0.03), which probability was 2.04 times higher in patients with IgA anti-β2-GP1. Verification of reliable APS was significantly associated with IgA aCL positivity (χ2 = 23.96; р < 0.0001) and IgA anti-β2-GP1 positivity (χ2 = 15.00; р < 0.0001). Despite the low sensitivity, a high specificity of IgA aCL and IgA anti- β2-GP1 was revealed in relation to APS diagnosis as well as its clinical manifestations. IgA aPLs were determined significantly more frequently in patients with positive IgG/IgM aCL and IgG/IgM anti-β2-GP1. IgA aCL and IgA anti-β2-GP1 levels significantly correlated with IgG/IgM aCL, IgG/IgM anti-β2-GP1, and to with IgG aPL in a greater degree. Isolated IgA aCL and IgA anti-β2-GP1 positivity was not observed. Conclusion. The relationship of thromboses and APS with IgA aCL and IgA anti-β2-GP1 was identified. A high specificity of IgA aCL and IgA anti-β2-GP1 (95% and 93%, respectively) in APS diagnosis was noted, while the sensitivity was low (54% and 44%, respectively). Isolated IgA aPL positivity was not revealed.

Обзор посвящён антифосфолипидным антителам (аФЛ) и их клинико-диагностической ценности. Рассматриваются вопросы стандартизации методов исследования аФЛ, в частности твердофазных тест-систем, одним из представителей которых является хемилюминесцентый анализ. Обсуждаются патогенетические аспекты антифосфолипидного синдрома (АФС) и описываются пути влияния аФЛ на различные компоненты гемостаза. Дается подробная характеристика β2-гликопротеина 1 (β2-ГП1) с описанием доменов. Подробно изучены клинические проявления и взаимосвязь «экстра»-критериальных аФЛ: IgA антител к кардиолипину (IgA-аКЛ), IgA антител к β2-ГП1 (IgA-аβ2-ГП1), антител к домену I β2-ГП1 (аβ2-ГП1-DI), антител к комплексу фосфатидилсерин–протромбин и аФЛ, не входящих в Сиднейские диагностические критерии АФС. Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia in which patients have clinical signs of recurrent thrombosis and morbidity during pregnancy and constantly test positive for antibodies against phospholipid (aPL). At least one clinical (vascular thrombosis or pregnancy) and one laboratory (positive test result for anticoagulant lupus, anticardiolipin antibodies and/or anti-β2-glycoprotein 1 antibodies) must be performed in order for the patient to be classified as having APS. However, the clinical and laboratory APS spectra cover additional manifestations. Research interest is increasingly focused on developing new assays that may be more specifi c to APS than current aPL tests. This review focuses on extra criterion antiphospholipid antibodies — IgA antibodies to cardiolipin (IgA-aCL), IgA antibodies to β2-glycoprotein 1 (IgA-aβ2-GP1), antibodies to phosphatidylserine-prothrombin complex. A detailed description of aβ2-GP1 with a description of domains is given. The questions of standardization of aPL research methods, in particular, solid-phase test systems, one of which is chemiluminescent analysis, are examined.

Вопросы по критериальным признакам антифосфолипидного синдрома (АФС), в частности о необходимости включения некоторых клинических проявлений, а также серологических маркёров, отличных от классических, остаются актуальными. В обзоре приведены предлагаемые профили некритериальных проявлений АФС, обсуждается необходимость пересмотра классификационных критериев АФС. Today questions about the antiphospholipid syndrome (APS) criteria remain actual. This applies in particular about the need to include some clinical manifestations, as well as serological markers that are distinguishable from those classic ones, in APS criteria. The review presents the proposed profiles of non-criterial APS manifestations, and discusses the need to revise APS classification criteria.

Введение. Антифосфолипидный синдром (АФС) — аутоиммунная патология сосудов, клинически проявляющаяся рецидивирующими тромбозами сосудов любой локализации и калибра и акушерской патологией — рецидивирующими потерями плода. В последние 2 десятилетия в патогенетических аспектах АФС обсуждается роль системы комплемента. Цель исследования: определить связь между клинико-лабораторными проявлениями АФС и уровнем компонентов комплемента. Материалы и методы. Обследованы 111 пациентов: 87 (78%) женщин и 24 (22%) мужчины; 31 (28%) пациент был с первичным АФС (пАФС), 63 (57%) — с АФС в сочетании с системной красной волчанкой (СКВ) и 17 (15%) — с СКВ без АФС. У всех пациентов определяли антитела к кардиолипину (аКЛ) классов IgG и IgM и антитела к β2-гликопротеину 1 (аβ2-ГП1) классов IgG и IgM иммуноферментным анализом (ИФА), а также уровни С3 и С4 компонентов комплемента нефелометрическим методом. Результаты. У 72 пациентов в анамнезе были зарегистрированы тромбозы: у 23 пациентов с пАФС, у 44 с СКВ + АФС, у 5 с СКВ без АФС. Снижение уровня С3 было выявлено у 61 (55%) пациента из 111: у 14 (23%) пациентов с пАФС, у 35 (57%) с СКВ + АФС, у 12 (20%) с СКВ. Снижение С4 установлено у 37 (33%) из 111 пациентов: у 4 (11%) с пАФС, у 24 (65%) с СКВ + АФС, у 9 (24%) с СКВ. Снижение уровня С3 значимо чаще определено у пациентов c пАФС, позитивных по IgG-аКЛ и IgG-аβ2-ГП1 (р < 0,05). Снижение уровня С4 также ассоциировалось с позитивностью IgG-аКЛ и IgG-аβ2-ГП1 у пациентов с пАФС. У пациентов с СКВ + АФС гипокомплементемия С3 ассоциировалась с IgM-аКЛ и IgM-аβ2-ГП1, а снижение уровня С4 компонента комплемента существенно чаще зарегистрировано у пациентов с IgG-аКЛ (р = 0,002) и IgG-аβ2-ГП1 (р = 0,0001). Гипокомплементемия у пациентов с СКВ без антифосфолипидных антител имела место более чем в половине случаев: у 12 из 17 (71%) выявлено снижение С3 компонента комплемента и у 9 (53%) — снижение С4. Заключение. Зарегистрировано снижение С3 больше чем у половины (55%) и снижение С4 у трети (33%) обследованных пациентов, что свидетельствует об активации системы комплемента при АФС. Наличие IgG-аКЛ и IgG-аβ2-ГП1 ассоциировалось с гипокомплементемией, что свидетельствует о значимости этих антител в механизме активации комплемента и запуске гиперкоагуляции через систему комплемента. Background. Antiphospholipid syndrome (APS) is an autoimmune vascular pathology that is clinically manifested by recurrent vascular thrombosis and pregnancy loss. The role of complement system in the pathogenesis of APS is discussed in the last 2 decades. Objectives: to find out the relationships between the clinical and laboratory manifestations of APS and the level of complement components. Patients/Methods. We examined 111 patients: 87 (78%) women and 24 (22%) men; among them were 31 (28%) patients with primary APS (pAPS), 63 (57%) with APS and systemic lupus erythematosus (SLE) and 17 (15%) with SLE without APS. In all patients, antibodies to cardiolipin (aCL) of IgG and IgM classes and antibodies to β2-glycoprotein 1 (aβ2-GP1) components by the nephelometric method. Results. 72 patients had a history of thrombosis: 23 patients with pAPS, 44 with SLE + APS, 5 with SLE without APS. Decreased C3 level was detected in 61 (55%) of 111 patients: in 14 (23%) patients with pAPS, in 35 (57%) with SLE + APS, and in 12 (20%) with SLE. Decreased C4 level was observed in 37 (33%) of 111 patients: in 4 (11%) with pAPS, in 24 (65%) with SLE + APS, and in 9 (24%) with SLE. Decreased C3 level was significantly more often registered in pAPS-patients positive for IgG-aCL and IgG-aβ2-GP1 (p < 0.05). Decreased C4 level was also associated with positivity for IgG-aCL and IgG-aβ2-GP1 in pAPS-patients. In patients with SLE + APS, C3 hypocomplementemia was associated with IgM-аCL and IgM-аβ2-ГП1 and decreased C4 level was significantly more often registered in patients with IgG-aCL (p = 0.002) and IgG-аβ2-ГП1 (р = 0,0001). Hypocomplementemia in patients with SLE without antiphospholipid antibodies occurred in more than half of the cases: decreased C3 level was revealed in 12 of 17 (71%) patients, and decreased C4 level — in 9 (53%) patients. Conclusions. Decreased level of C3 was registered in more than half (55%) and a decreased level of C4 — in a third (33%) of examined patients, that indicated the complement system activation in APS. The presence of IgG-aCL and IgG-aβ2-GP1 was associated with hypocomplementemia that evidenced the significance of these antibodies in the mechanism of complement activation and the triggering of hypercoagulation through the complement system.

In this scientific review we pursue the objective of studying the general pathogenetic, clinical-dynamic, prognostic and therapeutic aspects in the field of psychiatry and rheumatology. We identify the negative impact of mental disorders, above all – that of depression, on triggering, clinical manifestations, prognosis, and treatment of systemic lupus erythematosus, as well as the undoubtedly triggering and chronic impact of severe immune inflammatory pathology on anxiety and depressive disorders. In this regard, systemic lupus erythematosus and anxiety-depressive spectrum disorders patients have a lower quality and expectancy of life than patients with no mental pathology.

Uncontrolled hypercoagulation and inflammation (thromboinflammation), which are both independent and closely related and amplifying each other pathological processes, form the basis for pathogenesis of a wide range of diseases and complications, including immuno-inflammatory (autoimmune) rheumatic diseases, with the development of potentially fatal injuries of internal organs. Thrombotic microangiopathy is one of the most prominent prototypes of thromboinflammatory pathological conditions. The close link between environmental factors, hemostasis genetic defects and the complement system, inflammation and autoimmunity as pathogenetic mechanisms of microthrombosis draws particular attention to studying thrombotic microangiopathy in immuno-inflammatory rheumatic diseases, primarily systemic lupus erythematosus, antiphospholipid syndrome and scleroderma renal crisis. In future, these studies may be important for expanding the idea of the role of autoimmune mechanisms in pathogenesis of critical hemostasis disorders in human diseases, and for developing new approaches to therapy. Recently, special attention has been paid to the treatment of systemic lupus erythematosus and antiphospholipid syndrome with eculizumab, which is humanized monoclonal IgG2/4k antibody that blocks the complement component C5a and the membrane attack complex (C5b-9) formation, and which is registered for the treatment of atypical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria, as well as severe forms of myasthenia gravis and neuromyelitis optica. Further studies in this direction will create prerequisites for improving the prognosis not only in patients with orphan disorders, but also for widespread human diseases.

Приведен обзор литературы по механизму развития антифосфолипидного синдрома (АФС), тактика терапии. Представлены последние рекомендации Европейской антиревматической лиги (англ. European League Against Rheumatism, EULAR) по профилактике и лечению тромбозов при АФС. Обсуждены вопросы целесообразности терапии иммуносупрессивными препаратами при АФС. The review is dedicated the development and the treatment of antiphospholipid syndrome (APS), and the content of the recent guidelines of European League Against Rheumatism (EULAR) for prevention and treatment of thrombosis in APS. The immunosuppressive therapy advisability in APS is discussed.

Patients who have undergone large (hip, knee) joint replacement constitute a group at high risk for developing venous thromboembolic events (VTEs). According to different authors, the risk of nonpreventable VTEs in these patients varies from 40 to 80%. Objective: to analyze the incidence of VTE and the risk of postoperative wound-related bleeding and complications in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) after total hip arthroplasty. Subjects and methods. The investigation enrolled 486 patients with RA (n=212) and OA (n=274) who underwent primary hip arthroplasty. Each patient group was divided into three subgroups according to prevention with the following drugs: 1) nadroparin calcium; 2) dabigatran etexilate; 3) nadroparin calcium switched to dabigatran etexilate. According to the International Society on Thrombosis and Haemostasis criteria, intra- and postoperative blood loss was assessed during the first 7 days after surgery; the wound healing process was also evaluated. Results and discussion. VTE was prevented with the drugs in 239 (49.2%) patients, 130 (26.8%) of them received nadroparin calcium, the remaining 117 (24.0%) patients had dabigatran etexilate or both drugs. Postoperative VTEs were recorded in 36 (7.4%) out of the 486 patients. VTEs were detected significantly less frequently In RA than in OA (1.2 and 6.1%, respectively; p=0.0013). VTEs were more commonly asymptomatic in both groups. No fatal bleeding was seen in any patient, which confirms the safety of anticoagulant therapy. Blood transfusions were more frequently given to bleeding patients with RA than to those with OA (14.4 and 5.7% of cases, respectively; p<0.001). The number of patients with RA who required discontinuation of anticoagulant therapy was more than those with OA (6.6% and 1.4%, respectively). Delayed wound healing was also much more common in patients with RA (n=56; 26.4%) than in those with OA (n=14; 5.1%). VTE occurred much more often in patients receiving monotherapy with nadroparin calcium than in those having combined therapy (p<0.0001), and somewhat more frequently than in those taking dabigatran etexilate (p=0.054), however, the difference for the latter did not reach statistical significance. Conclusion. During elective hip replacement, VTEs occurred less frequently in patients with RA than in those with OA (1.23 and 6.17%, respectively, p=0.0013). After hip arthroplasty, VTEs were detected significantly more often in nadroparin calcium-treated patients with RA and OA than in patients receiving combined therapy. Postoperative wound-related bleedings were significantly more frequently observed in RA than in OA (14.4 and 5.7% of cases, respectively). The risk of postoperative wound-related complications in RA is much higher than in OA (relative risk, 4.33; 95% confidence interval, 2.67–7.03; p<0.001), which increases the length of hospital stay and the cost of the treatment performed.

Цель исследования: оценить значение гипергомоцистеинемии (ГГЦ) дополнительного фактора риска развития тромбоза при системной красной волчанке (СКВ) и антифосфолипидном синдроме (АФС). Материалы и методы. Обследовано 125 больных: 51 пациент с СКВ, 25 больных с изолированным первичным АФС (ПАФС) и 49 с сочетанием СКВ и АФС. Результаты. ГГЦ выявлена у 82 из 125 (66 ) пациентов: у 30 из 51 (59 ) больных СКВ, у 33 из 49 (67 ) пациентов с сочетанием СКВ и АФС и у 19 из 25 (76 ) больных с ПАФС. ГГЦ встречалась при СКВ у 86 мужчин против 60 у женщин (р 0,04). Содержание гомоцистеина (ГЦ) крови было выше (р 0,05) у больных СКВ с активностью от 11 до 20 баллов по шкале SLEDAI (20,3 8,4 мкг/л), чем у пациентов с активностью 510 баллов (14,5 5,8 мкг/л). ГГЦ достоверно чаще отмечалась у больных с дигитальными некрозами и дискоидной красной волчанкой. Уровень ГЦ у пациентов с СКВ не зависел от поражения почек. Повышение содержания ГЦ зарегистрировано у 43 из 55 (78 ) пациентов с АФС против 9 из 19 (47 ) больных с антифосфолипидными антителами без тромбоза (отношение шансов 3,98 95 ДИ 1,1613,98 р 0,03). ГГЦ чаще выявляли у пациентов с тромбозом церебральных артерий, артерий нижних конечностей, коронарных артерий, а также у пациентов с тромбозом нижней полой вены с синдромом БаддаКиари. Уровень ГЦ был выше у пациентов с артериальными тромбозами с посттромботическим периодом (ПТП) менее 2 мес (22,9 7,0 мкг/л), чем при ПТП более 2 лет (16,6 3,7 мкг/л). Заключение. Частота ГГЦ у обследованных пациентов составила 66 , преобладая у больных ПАФС (76 ). ГГЦ при СКВ ассоциировалась с мужским полом. ГГЦ может рассматриваться как самостоятельный фактор риска тромбоза как при первичном, так и при вторичном АФС. Повышение содержания ГЦ крови у пациентов с АФС ассоциировалось с церебральными тромбозами, тромбозом периферических артерий и ишемической болезнью сердца. Уровень ГЦ крови выше в первые месяцы после тромбоза по сравнению с отдаленным периодом после тромбоза (2 и более лет). Aim: to assess the importance of hyperhomocysteinemia (HHC) as an additional risk factor for thrombosis in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Materials and methods. We examined 125 patients: 51 patients with SLE, 25 patients with isolated primary APS (PAPS) and 49 patients with combination of SLE and APS. Results. HHC was revealed in 82 from 125 (66 ) patients: in 30 from 51 (59 ) patients with SLE, in 33 from 49 (67 ) patients with combination of SLE and APS, and in 19 from 25 (76 ) with PAPS. In lupus patients HHC was more often (p 0.04) in men (86 ) than in women (60 ). Homocysteine (HC) blood level was higher in SLE patients with the disease activity 1120 points according SLEDAI scale than in those with activity 510 points (20.3 8.4 vs. 14.5 5.8 g/l р 0.05). HHC was significantly more frequently observed in patients with digital necroses and discoid lupus erythematosus. HC blood level in patients with SLE did not depend of kidney involvement. Increasing of HC blood level was registered in 43 from 55 (78 ) patients with APS vs. 9 from 19 (47 ) patients with antiphospholipid antibodies without thrombosis (odds ratio 3.98 95 CI 1.1613.98 p 0.03). HHC was more frequently revealed in patients with cerebral, coronary and peripheral artery thromboses and also inferior vena cava thrombosis in patients with BuddChiari syndrome. HС blood level was higher in patients with arterial thrombosis with a postthrombotic period (PTP) less than 2 months (22.9 7.0 g/l) than in those with PTP over 2 years (16.6 3.7 g/l). Conclusion. HHC frequency in examined patients was 66 , predominantly in PAPS patients (76 ). HHC in SLE was associated with the male sex. HHC can be considered as an independent risk factor for thrombosis in both primary and secondary ASF. Increasing of HC blood level in patients with APS was associated with cerebral and peripheral arterial thromboses and coronary artery disease. HC blood content was higher in the first months after thrombosis as compared with the longterm period after thrombosis (2 years or more).

The review presents data about etiology and pathogenesis of antiphospholipid syndrome (APS) and genetic susceptibility to its development. The latest international criteria for diagnostics of AРC and its variants are presented. This syndrome can affect multiple organ systems depending on thrombosis localization; therefore nowadays APS problem is multidisciplinary. Clinical manifestations of APS are rather general (thromboses of different localization); so APS diagnosis can be verified only in presence of antiphospholipid antibodies. The differential diagnostics of APS is discussed.

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 of the principles and recommendations with commentaries of leading experts discussing characteristics of SLE in the Russian Federation and some debatable and unsolved problems.