Systemic lupus erythematosus (SLE) is a systemic autoimmune rheumatic disease of unknown etiology, characterized by hyperproduction of non-organ-specific autoantibodies to various components of the cell nucleus and the development of immune-inflammatory damage to internal organs. Currently, SLE is considered as a prototype of a systemic human autoimmune pathology, the central mechanism of immunopathogenesis of which is a violation of immunological tolerance to self-antigens, due to a complex interaction of genetic, epigenetic, environmental factors. The publication discusses the history of the study of SLE, the contribution of Russian scientists (V.A. Nasonova and others) to the study of th is problem, current trends in clinical and scientific research related to the improvement of diagnostic criteria and pharmacotherapy of this disease.

Inflammation and coagulation are key basic mechanism of protection against all potentially pathogenic mechanical and biological factors targeting human organism from inner and outer environment. On the other hand, uncontrolled inflammation results in hypercoagulation, inhibition of anticoagulation and alteration of mechanisms responsible for resolution of inflammation, while production of “procoagulant” mediators (thrombin, tissue factor and others), activation of platelets and of vascular endothelial cells maintains inflammation. All factors taken together serve as the basis for a pathological process called thromboinflammation or immunothrombosis. Currently thromboinflammation is considered in the broad sense as a universal pathogenetic mechanism of numerous widespread acute and chronic conditions, including immune-mediated (autoimmune) inflammatory rheumatic diseases, oftentimes complicated by severe irreversible damage to vital organs. Thromboinflammation gained specific attention during СОVID-19 (coronavirus disease 2019) pandemic, caused by SARS-Cov-2 (severe acute respiratory syndrome Coronavirus-2). COVID-19 is considered currently as systemic thromboinflammation syndrome, manifesting via generalized thrombosis of arterial and venous macro- and microvasculature, termed as COVID-19-coagulopathy. The paper discusses common pathogenetic coagulopathy mechanisms in COVID-19 and immune-mediated (autoimmune) inflammatory rheumatic diseases (IMRDs), associated with overproduction of antiphospholipid antibodies, activation of the complement system, and dis-regulated synthesis of proinflammatory cytokines, etc. Delineating the autoimmune subtype of thromboinflammation, identification of genetic (i.e., genes encoding the complement system and others) and molecular-biologic biomarkers associated with higher occurrence of COVID-19-coagulopathy are the most relevant undertakings for the current practice. Gaining insights into mechanisms of thromboinflammation and converting them into potential pharmacotherapies of IMDs would facilitate and accelerate the drafting of effective therapeutic strategies for COVID-19.

Objective: to study and analyze the dynamics of prevalence, demographic, social, and clinical manifestations of systemic lupus erythematosus (SLE) in patients living in Kazakhstan.Materials and methods. Official materials of the Ministry of Health of the Republic of Kazakhstan (2009–2018): statistical compendiums, a consolidated reporting form for medical treatment (N 12). 102 patients (100 women and 2 men) were included in the register of SLE with reliable SLE according to SLICC (ACR, 2012). Assessment of the debut of the disease was carried out according to archival material (medical history, outpatient records) of patients. The activity of the process was evaluated according to SLEDAI-2K, organ damage according to SLICC/ACR (2000).Results. The total number of patients with SLE over 10 years (2009–2018) more than doubled, the growth rate was 101%. The overwhelming majority of patients with SLE are women (91%). In the study group, Asians (83.33%) predominated by race, of which Kazakhs (76.47%) were young (mean age – 33.85±10.58 years), with a disease duration of 5 (2; 9) years, time from the appearance of the first signs to verification of SLE – 4.5 (3; 12) years. The prevailing acute (49.0%), subacute (33.3%), rather than chronic (18.7%) variants of the course, with high activity according to SLEDAI-2K – 17.64±8.80. The most common clinical manifestations of the disease: skin lesions (98%), joints (79.4%), nervous system (49%), hematological (54.9%) and immunological (100%) disorders. The absence of organ damage (0 points) was detected in 10 (9.8%) cases, low (1 point) – in 21 (20.6%), medium (2–4) – in 61 (59.8%), high (over 4) – in 10 (9.8%) patients.Conclusion. SLE remains a socially significant disease in Kazakhstan, as evidenced by the dynamics of the increase in incidence (101%) over 10 years (2009–2018). The prevalence of SLE is 24.7 per 100 thousand of the country’s population, lower than in other countries with a predominant Asian population or in comparison with Asian populations. A cohort of patients with SLE was represented by people of the Asian race (83.33%), Kazakhs (76.47%), and young people (33.85±10.58). The analysis revealed a delayed verification of the diagnosis of SLE (on average 4.5 (3; 12) years). Acute variants of the course of the disease with high disease activity according to SLEDAI-2K prevail. Common clinical manifestations of SLE are skin lesions, both acute and chronic (98%), joints (79.4%), damage to the nervous system (49%), hematological (54.9%) and immunological disorders (100%).

Immune-inflammatory (autoimmune and autoinflammatory) rheumatic diseases are widespread severe chronic inflammatory diseases and also models for studying the fundamental mechanisms of pathogenesis and approach to pharmacotherapy of other diseases associated with autoimmunity and/or autoinflammation. Uncontrolled inflammation leading to hypercoagulation forms the basis of thromboinflammation, which is considered a universal pathogenetic mechanism of organ involvement in immune-inflammatory rheumatic diseases, as well as in COVID-19 and atherosclerotic vascular lesions (atherothrombosis). Thrombo-inflammatory mechanisms play a crucial role in systemic lupus erythematosus and antiphospholipid syndrome. Russian rheumatology, under the leadership of academician Valentina Alexandrovna Nasonova, greatly contributed to the research of these disorders. This article addresses the current view about the overlapping pathogenetic mechanisms of thrombosis in systemic lupus erythematosus and antiphospholipid syndrome, the relevance of these studies during the COVID-19 pandemic, and the prospects for antithrombotic and anti-inflammatory therapy.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology characterized by the overproduction of autoantibodies against various components of the nucleus of the patient's own cells with the development of immunoinflammatory tissue damage. In recent years, more and more data have accumulated on the involvement of neutrophils in the development of the clinical symptoms of SLE, and DNA-containing structures and neutrophil extracellular traps (NETs) playing an important role in this process. Effective neutralization of NETs in SLE can be achieved by removing circulating proteins and molecules associated with NETs from the bloodstream by selective plasma sorption of DNA using the NucleoCapture Device.This article describes the case of a patient who underwent three plasma sorption sessions aiming to suppress the activity of SLE. During the therapy, significant positive dynamics were achieved: the SLEDAI-2K index decreased from 32 to 12 points, the number of leukocytes in the blood normalized, renal function improved, and the immunological activity of the disease decreased.

Lupus nephritis (LN) is the leading cause of death in systemic lupus erythematosus (SLE), so its early detection and treatment is of utmost importance. Features of the onset, clinical signs, certain morphological classes, as well as more aggressive therapy make it possible to assign SLE with LN to a distinct disease phenotype.Objective: to characterize the clinical, immunological and morphological features of the SLE phenotype with a predominant kidney involvement based on a comparative analysis of patients with LN and without LN.Patients and methods. The study included 400 patients with SLE who met the 2012 SLICC criteria and were hospitalized to V.A. Nasonova Research Institute of Rheumatology from 2013 to 2021. The diagnosis of LN was established in 192 (48%) patients, of which in 82 (43%) it was confirmed by pathological study of kidney biopsy specimens (the SLE group with LN). In 208 (52%) patients, no kidney damage was observed, and they constituted the SLE group without LN.All patients underwent a standard examination with an assessment of disease activity according to the SLEDAI-2K index, irreversible changes in organs according to the SLICC damage index, immunological disorders, clinical and biochemical blood tests, urinalysis according to unified methods, glomerular filtration rate, as well as pathological examination of kidney biopsy specimens for confirmation of LN in the presence of an appropriate clinical picture. In patients of both groups, a comparative study of the main clinical, laboratory, immunological manifestations of SLE, the features of the disease onset, its first clinical signs, possible trigger factors, and the drugs used was carried out.Results and discussion. In the LN group, insolation was more likely to trigger the development of SLE than in the group without LN (respectively, in 26% and 13% of cases; p=0.007). In turn, SLE without kidney damage more often than SLE with LN debuted during pregnancy or after childbirth.The first signs of the disease in almost 40% of patients with LN were proteinuria and/or changes in urinary sediment, edema, increased blood pressure, the development of LN in some cases was preceded by polyarthritis or combined lesions of the skin and joints, but no later than 6 months, signs of kidney damage appeared. In the SLE group without LN, polyarthritis (in 33%), combined lesions of the skin and joints (in 26%), and Raynaud's syndrome (in 16%; p <0.0001) were more often observed at the onset. In patients with LN, erythematous lesions of the facial skin ("butterfly", in 42%), serositis (exudative pleuritis — in 44%, pericarditis — in 46%, ascites and hydrothorax — in 5%; p<0.0001), as well as hematological disorders such as anemia (in 63%), leukopenia (in 49%) and thrombocytopenia (in 42%) were present more frequently. With the development of LN, an acute course and high activity of the disease occurred significantly more often. In the study of immunological parameters in the group without LN, lupus anticoagulant (in 6%) and antibodies to SS-A/Ro and SS-B/La (in 18 and 9% of patients, respectively) were detected significantly more often, while in the LN group — hypocomplementemia (in 81%; p<0.0001). Therapy also differed significantly: patients with LN received higher doses of glucocorticoids (p<0.0001), mycophenolate mofetil, and cyclophosphamide.Conclusion. SLE with LN can be considered a distinct disease phenotype with a set of characteristics (clinical and laboratory parameters, response to therapy, prognosis) that distinguish it from other SLE variants.