Immunoinflammatory Rheumatic Diseases Research Articles

Methotrexate and immunogenicity of vaccines in patients with rheumatic diseases

Currently, methotrexate (MT) remains one of the immunosuppressive drugs most commonly used in rheumatology. However, its effect on the immunogenicity of vaccines has until recently been studied only to a limited extent, which has led to the lack of clear recommendations for the use of MT during vaccination. Significant progress was made during the COVID-19 pandemic due to the dynamic development of vaccine research, including in patients with immuno-inflammatory rheumatic diseases. The review presents data on the effect of MT on the immunogenicity of vaccines against influenza, pneumococcus, herpes zoster, tetanus/diphtheria/pertussis, yellow fever and COVID-19 (including humoral and cellular responses) in rheumatological patients. The necessity of observing certain time intervals during vaccination in the case of MT use has been demonstrated. The potential mechanisms by which MT influences the immunogenicity of vaccines are presented. The importance of further clinical studies is emphasized in order to assess the effect of MT therapy on the vaccine response and to develop methods for its optimization.

Glucagon-like peptide-1 receptor agonists: Prospects for use in rheumatology

Glucagon-like peptide-1 receptor agonists (ArGLP-1) are effective drugs for the treatment of type 2 diabetes mellitus and obesity. Recent studies in patients with a wide range of immunoinflammatory diseases suggest important pleiotropic mechanisms of action of these drugs, primarily related to the suppression of inflammation. The article presents new data indicating the prospects for the use of ArGLP-1 in immunoinflammatory rheumatic diseases, which dictates the need for clinical studies. GLP-1 receptor agonists are effective drugs for the treatment of type 2 diabetes mellitus and obesity. Recent studies in patients with a wide range of immune-mediated diseases suggest important pleiotropic mechanisms of action of these drugs, primarily related to the suppression of inflammation. The article presents new data indicating the prospects for the use of ArGLP-1 in immune-mediated rheumatic diseases, which dictates the need for clinical studies.

Vaccinoprophylaxis of infections and activity of immuno-inflammatory rheumatic diseases: pro et contra

In modern conditions, patients with immuno-inflammatory rheumatic diseases (IIRD) are at significant risk of influenza, pneumococcal and herpes viral infections, as well as COVID-19, in some cases fatal. The most effective way to prevent infectious diseases and reduce mortality from them is vaccination, which is recommended in the inactive phase of IIRD. However, a number of patients with IIRD have a refractory course of the disease, and achieving remission in them turns out to be a difficult task, and therefore the problem of vaccination of such patients against the background of an active inflammatory process is very relevant. The review analyzes data on the use of vaccine prophylaxis for the above infections in the active phase of IIRD. In the vast majority of cases, vaccination was safe and did not lead to an exacerbation of IIRD or the development of new autoimmune phenomena.

Coronavirus disease 2019 (COVID-19) pandemic and autoimmune rheumatic diseases: Outcomes and prospects

The pandemic of coronavirus disease 2019 (COVID-19), etiologically related to the SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus-2), has drawn attention to new clinical and fundamental problems in the immunopathology of human diseases associated with virus-induced autoimmunity and autoinflammation. The provision that “the experience gained in rheumatology in the process of studying the pathogenetic mechanisms and pharmacotherapy of immunoinflammatory rheumatic diseases as the most common and severe forms of autoimmune and autoinflammatory pathology in humans will be in demand for deciphering the nature of the pathological processes underlying COVID-19 and developing approaches to effective pharmacotherapy” was confirmed in numerous studies conducted over the next 3 years in the midst of the COVID-19 pandemic. The main focus will be on a critical analysis of data regarding the role of autoimmune inflammation, which forms the basis of the pathogenesis of immune-mediated rheumatic diseases in the context of the immunopathology of COVID-19.

Experience with 23-valent pneumococcal polysaccharide vaccine in patients with ankylosing spondylitis and psoriatic arthritis

Pneumococcus plays a primary role as a causative agent of pneumonia both in the general population and in patients with immuno-inflammatory rheumatic diseases (IVRS), including spondylarthritis (SpA). However, data on the immunogenicity, efficacy and safety of pneumococcal vaccines in patients with SpA are limited.The aim of the study. To study the immunogenicity, efficacy and safety of the 23-valent pneumococcal polysaccharide vaccine (PPV-23) in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA), observed at the V.A. Nasonova Research Institute (Moscow, Russia).Materials and methods. 145 people were included in the study: 51 patients with AS, 25 with PsA, 69 in control group (СG) without IVR. The majority of patients (65.8%) received immunosuppressive therapy. PPV-23 was administered in an amount of one dose (0.5 ml) subcutaneously against the background of antirheumatic therapy, regardless of the activity of the main IVR. The level of antibodies (AT) to pneumococcal capsular polysaccharide was determined using the EIA PCP IgG kit (TestLine Clinical Diagnostics, Czech Republic) before vaccination and 1, 3 and 12 months after it. The clinical efficacy and safety of PPV-23 were also evaluated, including the effect on the activity of AS and PsA according to the dynamics of BASDAI and DAPSA indices.Results. After 1, 3 and 12 months after vaccination, the concentration of pneumococcal AT was significantly higher compared to baseline values, which indicates sufficient immunogenicity of PPV-23. The clinical efficacy of PPV-23 in patients with AS and PsA was 98.7%. In general, there was no negative effect of vaccination on the activity of the underlying disease. The frequency of postvaccinal reactions in patients and in СG was comparable.Conclusions. The obtained results of the study indicate sufficient immunogenicity, clinical efficacy and safety of PPV-23 in patients with AS and Ps A.

Pro-inflammatory activation of monocytes in patients with immunoinflammatory rheumatic diseases

The pathogenesis of immunoinflammatory rheumatic diseases (IRDs) is based on chronic inflammation, one of the key mechanisms of which may be abnormal activation of macrophages, leading to further disruption of the immune system.The aim – to evaluate the pro-inflammatory activation of circulating monocytes in patients with IRDs.Material and methods. The study included 149 participants: 53 patients with rheumatoid arthritis (RA), 45 – with systemic lupus erythematosus (SLE), 34 – with systemic scleroderma (SSc) and 17 participants without IRD, aged 30 to 65 years. Basal and lipolysaccharide (LPS)-stimulated secretion of monocytes was studied in a primary culture of monocytes obtained by immunomagnetic separation from blood. Quantitative assessment of the cytokines tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and the monocyte chemoattractant protein-1 (MCP-1) was carried out in the culture fluid by ELISA. Pro-inflammatory activation of monocytes was calculated as the ratio of LPS-stimulated and basal secretions.Results. It was shown that the basal secretion of all studied cytokines was significantly increased in all groups of patients with IRDs, except for the secretion of IL-1β in the SLE group, compared with the control. LPS-stimulated secretion of TNF-α was increased and MCP-1 was decreased in patients with IRDs compared to the control group; LPS-stimulated IL-1β secretion only in the SSc group was significantly different from the control group. In the RA group, monocyte activation was reduced for all cytokines compared to the control, in the SLE group – for TNF-α and MCP-1, in the SSc group – for MCP-1.Conclusion. The decrease in pro-inflammatory activation of monocytes in patients with IRDs is due to a high level of basal secretion of cytokines, which can lead to disruption of the adequate immune response in these diseases and is an important link in the pathogenesis of chronic inflammation.

Efficacy and safety of the Gam-COVID-Vac in patients with immunoinflammatory rheumatic diseases: preliminary data of prospective study

Objective: to study the efficacy and safety of the Gam-COVID-Vac vaccine in patients with immunoinflammatory rheumatic diseases (IRD) in a prospective study.Material and methods. The study included 42 patients with IRD and 57 individuals without IRD (control group) who received at least one component of Gam-COVID-Vac. Immunization with the first component of the vaccine was carried out from March 25th to August 1st, 2022, the second – 3 weeks after the first dose. On days 1, 3 and 7 after administration of the first and second components, the study participants provided information on adverse events (AEs) by telephone. All subjects were examined by a rheumatologist 1, 3 and 6 months after complete immunization. The observation period after immunization with the second dose was 6 months.Results and discussion. 42 patients received the first component of the vaccine, and 39 patients received two components. In the control group, 57 subjects were immunized with two components of the vaccine. 30–180 days after vaccination with two components of Gam-COVID-Vac, 3 (7.7%) patients were diagnosed with SARS-CoV-2 infection, which was confirmed by polymerase chain reaction. In all cases, a mild course of COVID-19 without signs of pneumonia was observed. There were no cases of COVID-19 in the control group. After immunization with the first component, a combination of at least one local and one systemic AE (SAE) was documented in 28.6% of patients with IRD and 33.3% of individuals in the control group (p>0.05). No AEs were recorded in 42.9% and 36.8% of cases respectively (p>0.05). After vaccination with the second component, a combination of ≥1 local AE and SAE was recorded in 15.4 % of patients with IRD and 22.8% of individuals in the control group (p>0.05). No AEs occurred in 71.8% and 56.1% of cases respectively (p>0.05). In 10.3% of patients with IRD and 12.3 % of those without IRD (p>0.05), a combination of local and systemic AEs was recorded after the introduction of both first and second components. No AEs were observed in 35.9% and 28.1% of cases, respectively (p>0.05). The overall rate of IRD exacerbations was 4.8%.Conclusion. Based on the available data, vaccination against COVID-19 appears to be effective and quite safe in patients with IRD.

Frequency and course of COVID-19 in patients with rheumatic diseases (according to the data of V.A. Nasonova Research Institute of Rheumatology)

The aim of the study was to assess frequency and severity of COVID-19 in patients with rheumatic diseases (RD) who were on inpatient treatment at the V.A. Nasonova Research Institute of Rheumatology. Patients and methods. The study included information on the presence or absence of COVID-19 in the medical history of 6911 patients with immunoinflammatory RD (IIRD) and 362 patients with osteoarthritis (OA) who were on inpatient treatment at the V.A. Nasonova Research Institute of Rheumatology from September 21, 2021 to April 28, 2023. Results. The incidence of COVID-19 in the analyzed IIRD was significantly higher compared to OA (p<0.001). All IIRD included in the analysis are characterized by an increased risk of COVID-19 incidence when compared with OA by 2.7–6.3 times. Patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, microcrystalline arthritis, Sjögren’s disease, systemic sclerosis, systemic lupus erythematosus, and ANCA-associated vasculitis were significantly more likely (p<0.02) to receive COVID-19 therapy compared with the control group. Patients with these diseases are characterized by an increased risk of treatment for COVID-19 by 1.9–3.7 times compared with OA. Also, patients with inflammatory joint diseases (IJD), connective tissue diseases (CTDs) and systemic vasculitis (SV) were hospitalized with COVID-19 more often than patients with OA (p=0.01, p=0.007 and p=0.024, respectively). Patients with IJD, CTDs and SV are characterized by an increased risk of hospitalization with COVID-19 by 4.3– 4.7 times compared with OA. In addition, elderly patients with IIRD are characterized by an increasing risk of treatment, hospitalization and use of biologics or targeted synthetic disease-modifying drugs for COVID-19. Conclusion. According to the results obtained, the problem of COVID-19 is significant for patients with RD, which dictates need for further research on vaccination against SARS-CoV-2 among this cohort of patients.

The role of NETosis in the pathogenesis of immunoinflammatory rheumatic diseases

Uncontrolled activation of neutrophils is considered an important mechanism of thromboinflammation and fibrosis in immunemediated rheumatic diseases (IMRD), malignant neoplasms, atherosclerosis, COVID-19 and many other acute and chronic inflammatory diseases of humans. Particular attention has been drawn to the ability of neutrophils to form “network” (web-like) structures, called “neutrophil extracellular traps” NETs. The process associated with the formation of NETs and the weakening of their degradation is called “NETosis”. The publication summarizes data on the role of NETosis in the pathogenesis of IMRD and discusses the prospects for pharmacotherapy aimed at preventing the formation and destruction of NETs.

Scleritis in children: Etiology, pathogenesis, clinical features, diagnostic, and treatment algorithm

AIM: To analyze the etiology and pathogenesis and identify clinical and diagnostic features, development of a diagnostic algorithm, and personalized treatment of scleritis in children.
 MATERIALS AND METHODS: Twelve children with mono- and bilateral scleritis with disease duration of 39 months were observed. Biomicroscopy, ophthalmoscopy, and ultrasonography of the eyes were performed. The examination plan included consultations with a rheumatologist, otorhinolaryngologist, and dentist and laboratory blood analysis in the enzyme immunoassay to detect the presence of IgG and IgM antibodies to herpes viruses and markers of their reactivation.
 RESULTS: Chronic scleritis in 58.4% of the patients was associated with immunoinflammatory rheumatic diseases: 41.7% with juvenile idiopathic arthritis and 16.7% with psoriatic arthritis. In some cases scleritis was associated with chickenpox, surgical treatment of congenital pigmented nevus of the skin of eyelids,n on the conjunctiva and oculomotor muscles, otogenic neuritis of the facial nerve. Сlinical features of anterior deep scleritis and symptoms of bacterial scleritis are described. Personalized schemes for the diagnosis and treatment of scleritis in children have been developed. Conservative treatment included instillation of glucocorticoids and non-steroidal anti-inflammatory drugs. In addition, to anti-inflammatory therapy, antibacterial drugs are prescribed only in the presence of clinical signs of bacterial scleritis; in other cases, their use is inappropriate. The indications for antiviral therapy included laboratory confirmation of herpes infection reactivation. Personalized etiotropic therapy made it possible to achieve remission of scleritis in 914 days.
 CONCLUSION: This study analyzed the etiopathogenesis of scleritis, described the characteristic clinical features of anterior deep scleritis in children, and developed personalized diagnostic and treatment schemes.

Sterile inflammation, cross-presentation, autophagy and adaptive immunity in immunoinflammatory rheumatic diseases

Proinflammatory extracellular and intracellular DAMPs are the dominant etiological factors of sterile inflammation in immuno-inflammatory rheumatic diseases. They are generated by systemic progressive disorganization of loose fibrous unformed connective tissue, programmed cell death and cell necrosis. Sterile inflammation is a multi-stage process which is induced by a sequence of reactions mediated by leukocytes and resident cells of the macrophage-monocyte series, aimed at cleansing the focus of inflammation from cellular and tissue detritus, followed by restoration of homeostasis of damaged tissue. An important role in this process belongs to the transendothelial migration of leukocytes to the focus of sterile inflammation and formation of cellular inflammatory infiltrate. The key feature of these events is the reactivity of PRR receptors followed by a cascade of PRR-DAMPs interactions with subsequent launch of molecular and cellular processes causing the local and/or systemic manifestations of sterile inflammation. Activation of innate immunity is the result of PRR-DAMPs interactions which launches the molecular and cellular reactions. Hence, it is possible to attribute the immunoinflammatory rheumatic diseases to the category of systemic sterile autoinflammatory processes. Generalization of the pathophysiological effects of pro-inflammatory DAMPs and, accordingly, the systemic and multi-organ nature of tissue and internal organ damage in immunoinflammatory rheumatic diseases is due to the wide occurrence of receptors for “danger signals”. The most important place in the development of DAMP-mediated sterile inflammation is occupied by the phenomenon of cross-presentation and autophagy. The cross-presentation causes exposition of extracellular DAMPs from internalized proteins with MHC class I molecules to autoreactive CD8+ cytotoxic T lymphocytes. Autophagy provides processsing of intracellular peptide DAMPs, their loading onto MHC class II molecules with subsequent induction of adaptive immune response in CD4+T cell populations. The innate lymphoid cells (ILC) make an important contribution to these processes. The model of functional coupling and complementarity between ILCs and Th-CD4+T cells has expanded our understanding of immune regulation by extending the activity of innate and adaptive immunity to the level of maintaining tissue homeostasis, morphogenesis, repair, regeneration and inflammation. Progression of systemic sterile inflammation may be a result of PRR-DAMP interactions of tissue ILCs followed by switching of ILC/Th-CD4+T cell partners. The data presented in this review define the promising molecular and cellular targets aiming for regulation and/or inhibition of sterile inflammation in immunoinflammatory rheumatic diseases.

Rheumatoid arthritis and COVID-19: Three years later

During the three years that have passed since the beginning of the COVID-19 pandemic, many new fundamental and medical problems have been discovered regarding the relationship between the viral infection and many common chronic non- infectious diseases. Among the latter, an important position is occupied by immuno-inflammatory rheumatic diseases (IIRD), which include rheumatoid arthritis (RA). To date, there is no doubt that patients with RA are at risk for SARS-CoV-2 infection, a severe course of infection that necessitates hospitalization and death. The article presents current data on the course and outcomes of COVID-19 in patients with RA. The literature and own data on postcovid syndrome in this group of patients are presented. The necessity of vaccination against SARS-CoV-2 in patients with IIRD, including those with RA, was substantiated. The prospects for further study of the features of COVID-19 in patients with RA are outlined.

DNA double-strand breaks in immunoinflammatory rheumatic diseases

Objective: To study the frequency of spontaneous foci of DNA double-strand breaks (DSBs) in patients with immune-inflammatory rheumatic diseases (IIRD), their relationship to disease activity, levels of inflammatory markers, and levels of autoantibodies.Material and methods. The analysis included 40 patients with IIRD, including 19 patients with rheumatoid arthritis (RA, including 16 women, median disease duration 60 [20; 103] months, DAS28 was 5.05 [4.06; 5.9]) and 21 patients with systemic lupus erythematosus (SLE, 19 women, median disease duration 96.0 [40.0; 158.0] months, SLEDAI-2K 8.0 [4.0; 12.0]). The control group consisted of 17 healthy donors matched for sex and age.DNA DSBs were identified as discrete foci by immunofluorescence staining of lymphocyte cultures with antibodies against γH2AX and 53BP1 and subsequently analysed using the automated AKLIDES automated platform (Medipan).Results and discussion. There were no significant differences in the number of spontaneous DNA DSBs in patients with RA and healthy donors (p>0.05), a lower number of cells with the 53BP1 focus and a lower percentage of cells damaged in this focus were found in patients with SLE than in controls. There was a positive correlation between the number of γH2AXdamaged cells and CDAI(r=0.45, p=0.035), the number of cells with 53BP1 ruptures and the level of rheumatoid factor IgM (r=0.63, p=0.005) and ESR (r=0.53, p=0.02). In the group of SLE patients, a positive correlation was observed between the number of cells with breaks in the γH2AX focus and the level of antibodies against double-stranded DNA (anti-dsDNA; r=0.56, p=0.007), the average number of breaks in the cell in the γH2AX focus with the level of anti-dsDNA (r=0.57, p=0.004).Conclusion. The number of DNA DSBs may be an additional indicator of IIRD activity. In patients with SLE, DNA repair processes appear to be impaired, which is associated with the high activity of the disease.

The use of the combined vector vaccine GamCOVID-Vac (Sputnik V) in patients with immuno-inflammatory rheumatic diseases: safety issues-news

The aim of the study was to assess the safety of the combined vector vaccine Gam-COVID-Vac (Sputnik V) and to determine the risk factors for the development of adverse events in patients with immuno-inflammatory rheumatic diseases (IIRD). Patients and methods. A single-stage study of patients with IIRD who were on inpatient treatment or who applied to the consultative and diagnostic center of the V.A. Nasonova Research Institute of Rheumatology was conducted, who received both components of the Sputnik V vaccine. The control group included immunized persons without IIRD. All participants were interviewed by a research doctor with filling out a unified questionnaire, additional information was obtained from medical documentation. Results. The study included 325 patients with IIRD and 138 healthy controls. After vaccination with the first component, the number of patients with IIRD, in whom the development of local and systemic adverse events (AEs) was noted, was significantly lower compared to the control (20.3% and 38.4% respectively; p<0.001). These differences also persisted after immunization with the second component (12.3% and 28.3% respectively, p<0.001). After complete vaccination, no AEs were documented in 40.3% of patients and 22.5% of the control group (p<0.001). Female sex and, possibly, methotrexate therapy increases the risk of developing local and systemic AEs on the first component of the vaccine, rituximab therapy - on the second. A lower incidence of AEs is typical for elderly patients, patients with a disease duration of more than 10 years and obesity. Exacerbation of IIRD was registered in 1 (0.3%) case, the occurrence of new autoimmune phenomena was not observed. Conclusions. According to the data obtained, the use of Gam-COVID-Vac (Sputnik V) in patients with IIRD is safe.

Vaccination of pneumococcal infection in patients with systemic lupus erythe matosus and antiphospholipid syndrome: experience of 6 years of use

Infections remain one of the main causes of morbidity and mortality in patients with immuno-inflammatory rheumatic diseases. Objective – to study the efficacy, immunogenicity and safety of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (AРS). Materials and methods. 91 patients were included in the study: 78 with SLE, of which 18 (23 %) – with secondary AРS, 13 – with primary AРS. 85 patients received immunosuppressive therapy, including 30 – genetically engineered biological drugs (bDMARD); 23 – anticoagulants. PPV-23 was administered subcutaneously, patients were observed for a year after vaccination. Results. Local reactions were observed in 49% of patients with SLE and secondary AРS, in 23% of patients with primary AРS. General reactions were noted in isolated cases, were short-term and did not require additional prescriptions. During the follow-up period, no exacerbations of SLE, relapses of thrombosis and thromboembolism associated with vaccination were detected; no development of new autoimmune diseases was registered. 10 (13%) patients with SLE were immunized against the background of high activity of the disease, no adverse reactions were recorded. In some patients, a transient increase in a-DNA and ANF was observed during the year without signs of exacerbation of the disease. 56% of patients with SLE and secondary AРS, 15.4% with primary AРS were “responders” to the vaccine. There was no negative effect on the immune response of the dose of GC >10 mg/day, age, duration and activity of the disease. With the treatment of bDMARD, a full-fledged vaccine response was recorded much less frequently than with standard therapy (38% and 67.4%, respectively; p=0.01). After vaccination, there was a significant decrease in the number of lower respiratory tract infections (LRTI) (p=0.0001), including community-acquired pneumonia (PN) (p=0.03) and acute bronchitis (p=0.04), ENT infections (p=0.001). In the treatment of rituximab (RTM), compared with belimumab (BLM), a greater number of LRTI was observed, mainly due to PN. After vaccination on RTM therapy, the number of INDP in general (p=0.008) and PN in particular (p=0.03) decreased, isolated cases of LRTI and ENT organs were recorded on BLM therapy. Within 4–6 years after vaccination, 30 patients with SLE retained the clinical effect of vaccination, while immunogenicity decreased to 18%. Conclusion. Safety, sufficient immunogenicity, and clinical efficacy of PPV-23 in patients with SLE and AРS have been shown. The use of bDMARD reduces the vaccine response. Immunization performed prior to or during treatment with bDMARD lasting <1 year increases the number of vaccine responders.

To the 100th anniversary of the birth of academician V.A. Nasonova. Osteoporosis: Yesterday, today, tomorrow

Osteoporosis (OP) is the most common bone disorder associated with an increase bone fragility and a high fracture risk, which can be an isolated condition or a comorbidity of immuno-inflammatory rheumatic diseases. A great contribution to the study of OP in the Russian Federation was made by V.A. Nasonova, L.I. Benevolenskaya and scientific researchers of the Institute of Rheumatology. The article presents the main achievements that have occurred over the past 30 years in the development of this problem in our country and abroad, and the perspectives of osteoporosis treatment.

Evaluation of impact of new coronavirus infection on clinical course of rheumatic diseases in real clinical practice

Aim. To evaluate the effect of COVID-19 on the clinical course of immunoinflammatory rheumatic diseases (IRD).Material and methods. The clinical course of IRD was analyzed in 324 patients who underwent new coronavirus infection (NCI) from March 2020 to February 2021 and were treated at Clinical Rheumatology Hospital No. 25 (Saint-Petersburg, Russia) for exacerbation of the underlying disease.Results. The risk factors of severe COVID-19 course in IRD were: age older than 60 years, presence of comorbid conditions (IHD, CHD, COLD), use of glucocorticoids in dose more than 12.5 mg per day and erythrocyte sedimentation rate values ≥ 40 mm/h before development of NCI. The use of immunosuppressive therapy and biological therapy had no effect on the worsening of the course of the viral infection in patients with IRD. The development of post-covid syndrome (asthenia, dyspnea, weight loss, memory loss) was noted in ¼ of the patients. Post-covid articular syndrome was characterized by the formation of arthritis associated with viral infection in 3.6% of patients, transformation of undifferentiated arthritis (UDA) into specific nosological forms in 49.0% (more often into early rheumatoid arthritis, RA), and exacerbation of joint syndrome in 83.4% of patients with advanced stage RA. In patients with diffuse connective tissue disease (DCTD), a significant increase in immunological activity due to antinuclear antibodies (maximum 1: 163840) was noted. We present clinical cases of arthritis associated with viral infection and fatal outcome in a patient with systemic sclerosis and interstitial lung damage after COVID-19.Conclusions. In the cohort of patients with IRD observed at Clinical Rheumatology Hospital No. 25 (Saint-Petersburg, Russia) COVID-19 had a moderate to severe course in half of patients, initiated the development of pneumonic complications in 68.6% of patients, arthritis associated with viral infection in 3.6%, transformation of UDA into IRD in 49.0% of cases and exacerbation of the main disease in the great majority of patients. Patients with DCTD with interstitial lung damage have a high risk of adverse outcome of NCI, especially in cases of unstable course of the disease, pronounced immunosuppression and require special monitoring.The authors present their own clinical experience with the use of Alflutop in a comorbid patient with osteoarthritis and increased pain after undergoing CCI, which indicates its effectiveness and cardiovascular safety. An important practical advantage of Alflutop should be considered the absence of its effect on the parameters of hemocoagulation and the reduction in the need for NSAIDs, which reduces the risk of thrombotic complications characteristic of long-term COVID. A short course of Alflutop (ten intramuscular injections of 2.0 ml every other day) contributes to ease of use and increased adherence to therapy in patients with osteoarthritis.

Relationship between systemic inflammatory response and hypercoagulation in patients with immuno-inflammatory rheumatic diseases

The relationship between the processes of coagulation and inflammation protects the organism from potentially dangerous biological agents. However, hyperinflammation leads to an increase in the procoagulation potential, and activation of hemostasis factors maintains the inflammatory process. This phenomenon is called “immunothrombosis” or “ thromboinflammation”. The study of thromboinflammatory mechanisms is an actual problem of modern medicine, because in the future it will help to improve the therapy of diseases, in the pathogenesis of which thromboinflammation plays a significant role. The aim: to carry out a comparative analysis of the severity of the systemic inflammatory response in patients with immuno- inflammatory rheumatic diseases depending on the manifestations of hypercoagulation.To achieve the aim, a comparative analysis of proinflammatory markers (IL-6, IL-8, IL-10, TNFα, sIL-2R, CRP, ECP, β2-microglobulin) in the blood of patients with immune-inflammatory rheumatic diseases (systemic lupus erythematosus, rheumatoid arthritis, reactive arthritis, ankylosing spondylitis, psoriatic arthritis, rheumatic heart disease) was performed. Based on these inflammatory markers according to the authors' original methodology, the integral index of systemic inflammatory response (SIR) — Reactivity Level (RL) — was calculated. The cohort was divided into 2 groups: with the presence of signs of hypercoagulation and without signs of hypercoagulation according to the presence of elevated D-dimer level (> 500 ng/mL). Control group — healthy blood donors.The results of the study showed that SIR develops in patients with immuno-inflammatory rheumatic diseases regardless of the blood hemostatic potential. Patients with signs of hypercoagulation were characterized by higher values of most proinflammatory molecular markers, as well as increased integral level of SIR, which indicates a strong relationship between coagulation processes and inflammation at the systemic level. In addition, the probability of hypercoagulation increases with increasing severity of SIR (assessed by means of the integral index — RL). Thus, there is a transition of quantitatively more pronounced signs to a new qualitative level of pathological process development.The pathogenesis of immuno-inflammatory rheumatic diseases is characterized by the development of SIR (hypercytokinemia, acute phase response, intravascular leukocyte activation), the severity of which is closely related to intravascular microthrombosis.

The Methotrexate Story: How did a Cancer Chemotherapeutic Agent Become a Disease-modifying Antirheumatic Drug

Abstract Weekly mini-pulse of low-dose methotrexate (LD-MTX) is presently the first-line conventional synthetic disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA) and several other systemic immunoinflammatory rheumatic diseases (SIRDs). Yet, most of the younger generation of rheumatologists around the world may be unaware of the interesting journey of MTX, from being an antifolate agent for use as cancer chemotherapy to becoming the mainstay of treatment for inflammatory arthritides and other SIRDs. This short essay narrates the journey of MTX from its precursor analog aminopterin to treat childhood leukemia, its name change from aminopterin to MTX, which became one of the major chemotherapeutic agents in oncology and then evolving as the mainstay of drug treatment for RA and other SIRDs. The seminal role of Gubner et al. from New York in 1953 in recognizing its steroid-sparing property in inflammatory diseases at doses much lower than that needed to treat cancer is highlighted.

On the issue of screening and prevention of chronic and opportunistic infections in rheumatology

The problem of comorbid infections in rheumatology still remains relevant. Against the background of immunosuppressive/immunomodulatory therapy of immuno-inflammatory rheumatic diseases (IIRD), chronic and opportunistic infections (COI) often develop. Some of these infections can be prevented by performing timely screening procedures and preventive measures. A group of experts from the European Alliance of Rheumatology Associations (EULAR) has prepared recommendations on screening procedures and prevention measures for the most common COI (tuberculosis, chronic viral hepatitis B and C, infections caused by the human immunodeficiency virus and Herpes zoster, pneumocystis pneumonia) within the framework of the IIRD. This article presents the main provisions of this document. The need for periodic review of screening and preventive procedures is emphasized as new scientific data are accumulated.