Patient's reported outcomes – a new philosophy for analyzing the effectiveness of therapy in immunoinflammatory diseases

A fundamentally important task of modern pharmacotherapy of immunoinflammatory diseases (IID) is a significant improvement in the quality of life (QOL) of patients, the fastest and most complete elimination of the most unpleasant manifestations of the disease, restoration of function and working capacity. Specialists in the therapy of various IID took part in panel dedicated to the discussion of this problem: Professor E.L. Nasonov, PhD., member of the Academy of Science; Professor A.M. Lila, PhD; V.N. Amirjanova, PhD; A.E. Karateev, PhD; T.V. Korotaeva, PhD; O.V. Knyazev, PhD; T.A. Lisitsyna, PhD; M.M Hobeish, PhD; E.S. Filatova. PhD.One of the central issues was the discussion of the need to use the patient's reported outcomes (PROs) indicator in analyzing the results of IID therapy (rheumatoid arthritis, psoriatic arthritis, psoriasis and inflammatory bowel disease). The need for its use is due to the fact that the principal goal of treatment with modern disease modifying antirheumatic drugs (DMARDs) is not only to achieve low activity or remission of IID, but also to maximize the general condition and QOL of patients. Therefore, such manifestations of IID as pain, fatigue, dysfunction, depression and anxiety, etc., must be analyzed in the course of treatment. The development of these symptoms is determined by the main immunopathological process and is associated, among others, with systemic overproduction of a number of pro-inflammatory cytokines. Modern DMARDs: Janus kinase (JAK) inhibitors, in particular tofacitinib, are capable of directly blocking the effect of cytokines on cells (suppressing the intracellular JAK / STAT signaling pathway), quickly and effectively eliminating pain, fatigue and dysfunction. The use of JAK inhibitors seems to be especially appropriate in patients with IID with high inflammatory activity and severe clinical manifestations.

Features of case management with neuromuscular disease during Covid-19. Clinical impression.

The new COVID-19 coronavirus infection, which has become a pandemic, is a very dangerous disease, the clinical picture of which can vary from mild to extremely severe forms of the course. Currently, there is no complete data on the pathogenetic mechanism of SARS-CoV-2 virulence, but there is probable data on risk factors for the development of extremely severe forms of COVID-19. The study of such factors becomes most suitable in terms of preventing the development and influence on the course of the disease in immunocompromised individuals and patients with impaired neuromuscular transmission. The article describes two clinical cases of extremely severe COVID-19 in patients with impaired neuromuscular transmission. Based on the analysis of the course of diseases, conclusions are made about the possible aggravation and mutual activation of the immunopathological process with the launch of the cascade mechanism of the "cytokine storm". An assumption has been made about the influence of HLA on the severity of COVID-19, which is confirmed by positive dynamics against the background of the introduction of IVIG, GCS, virusinactivated plasma, and extracorporeal detoxification methods.

NON-SPECIFIC PROTECTION FACTORS AND INFLAMMATORY MEDIATORS IN URINE OF CHILDREN WITH GLOMERULONEPHRITIS IN THE PRESENCE OF HERPESVIRAL INFECTION NOTICE 2. DETERMINATION OF THE LEVEL OF IL-8 AND SLPI

The aim of this work was the study of indicators characterizing the local immunity in patients with various forms of glomerulonephritis by presence of herpesviral infection. Materials and methods. A quantitative estimation of the content of IL-8 and SLPI in urine of 47 patients with glomerulonephritis and 10 apparently healthy individuals was conducted. Results. A insignificant increase of IL-8 level in urine was showed in patients with glomerulonephritis. The level of urinary SLPI was reliably higher than the control value, at the same time the majority ofpatients (74,0 %) did not exceed the upper limit of the physiological norm. The essential increase ofIL-8 level in urine was observed in 13 sick children, and of SLPI – in 12 patients. The increase of IL-8 and SLPI levels was observed more frequently in patients with hematuric form of glomerulonephritis, with nephrotic steroidoresistant variant of nephrotic form, in the absence of remission, and in the case of IL-8 - with severe course of the disease. More such changes were found in children with active (reactivated) herpesviral infections. Conclusion. There has been confirmed the importance of the study of immunologic parameters in the urine of patients with glomerulonephritis to characterize immunopathological process in the kidney and prognosis of the disease.

NON-SPECIFIC PROTECTION FACTORS AND INFLAMMATORY MEDIATORS IN URINE OF CHILDREN WITH GLOMERULONEPHRITIS IN THE PRESENCE OF HERPESVIRAL INFECTION. NOTICE I. DETERMINATION OF SIGA AND MCP-1

The aim of this work was the study of indicators characterizing the local immunity in patients with various forms of glomerulonephritis by presence of herpesviral infection. Materials and methods. A quantitative estimation of the content of sIgA and MCP-1 in urine of 47patients with glomerulonephritis and 10 apparently healthy individuals was conducted. Results. The decrease of sIgA level and reliable increase ofMCP-1 level were observed in urine of patients with glomerulonephritis. There was a significant increase in the level of these indices in hormone-resistant patients with nephrotic form of glomerulonephritis; in patients with severe course of the disease and also in the absence of remission. More such changes were found in children with active (reactivated) herpesviral infections. Conclusion. There has been confirmed the importance of the study of immunologic parameters in the urine of patients with glomerulonephritis to characterize immunopathological process in the kidney and prognosis of the disease.

Features of a course of pregnancy at bronchial asthma and influence of immunological deposits on a placentary barrier

Studying of features of a course of pregnancy at the bronchial asthma (BA) and influence of immunological deposits on a placentary barrier was a research objective. Results of this research testify that the main complications of pregnancy at women with bronchial asthma is pregnancy interruption threat, gestosis and placentary insufficiency. Prevention, timely identification of these complications, joint maintaining patients by the obstetrician and pulmonologist allow women practically in all cases to give birth to the full-term healthy children. The greatest number of the immune deposits fixed in a placenta and damaging structures of a placentary barrier (endoteliya of vessels and a membrane of a sintsitiotrofoblast) is found in women with an average and a heavy current BA. Their adjournment is followed by morphological features of an immune inflammation, violation of an immune homeostasis in structures of a placentary barrier. Existence of pathogenic immune complexes in a placenta, and also detection with BA leads an antigen-presenting cells of cages in places of an immune inflammation at women to development of immunopathological process and placentary insufficiency that adversely affects the course of pregnancy, childbirth and can be a predictive factor of development of allergic diseases in the child.

The Immunomorphological condition placentae of the women connected with tobacco smoking

Immunomorphological, histologic research with application of semi-thin cuts bioptats placentae of the women connected with tobacco smoking to pregnancy, during all pregnancy and in the I trimester of pregnancy is carried out. Immunomorphological researches of placentae of studied groups showed that the greatest percent of the revealed fixed pathogenic immune complexes (PEAK) including existence fibrinogen, C3 fraction of a compliment, antibodies and pro-inflammatory citokins, were observed in group of women which smoked all pregnancy. The smallest percent of identification PEAK was in a placenta of the women, stopped to smoke to pregnancy. By parallel kliniko-laboratory comparison it is established that the greatest frequency of complications of pregnancy is observed at women who smoked all pregnancy. At histologic research of placentae of women of studied groups in the field of adjournment the PEAK is observed tsirkulyatorno-dystrophic and necrotic processes. The most widespread changes of a placenta are found at the smokers which pregnancy became complicated the gestozy. In the field of adjournment the PEAK leads damages of membrane structures of a placentary barrier to destructive changes of a placenta, to development of immunopathological process with violation of an immune homeostasis and to development of placentary insufficiency that is adversely reflected in an outcome of pregnancy and childbirth, and also on a fruit and newborn condition.

Clinical, humoral and IFN g responses of cattle to infection with Mycoplasma mycoides var. mycoides small colony and attempts to condition the pathogenesis of the infection

Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides var. mycoides small colony (MmmSC), is one of the most important diseases of cattle in Africa. The role of innate or acquired cell mediated and humoral immunity in conferring protection against MmmSC infection has not yet been elucidated. On the other hand, the pathological lesions caused by the aetiological agent have been considered indicative of an immunopathological process. In this study ten naïve cattle were exposed to in-contact infection with animals infected by intubation with a strain of MmmSC. Clinical signs, antibody response, IFNg release and pathological changes at necropsy were analysed and compared with the events following in-contact infection of an equal number of animals kept under daily treatment with cyclosporine for the entire observation period of 84 days. Cyclosporine is a suppressor of the immune response related to the T-cell system. Under the conditions of the experiment, cyclosporine appeared to condition the pathogenesis of CBPP by delaying the events that follow infection, bringing further support to the possibility that the immune response may have an impact on the disease outcome.

Endothelial hemostatic properties in diffuse toxic goiter

Changes in endothelial functional activity and lesion were studied in 38patients with diffuse toxic goiter (DTG) in the presence of thyrotoxicosis. There was an increase in CD4/CD8 ratios and the count of cells carrying CD+ and HLA-DRA. The blood levels of tumor necrosis factor-a (TNF-a) and IL-8 were also significantly higher in thyrotoxicosis than those at remission. There was a significant correlation between the blood levels of thyroid hormones and the higher blood concentration of PAI-1 and a negative correlation with the content of PAI-1, which is indicative of an increase in the blood fibrinolytic potential. There was a considerable rise in the count of circulating endotheliocytes in hyperthyroidism, which was associated with enhanced endothe- liocytic lesion due to the development of immunopathological changes and to the higher blood levels of thyroid hormones. The changes in the blood levels of t-PA, PAI-1, and circulating endotheliocytes may be used as markers of the severity of endothelial lesion, in characterizing the activity of an immunopathological process, and in predicting the development of vascular diseases in DTG.