The problem of studying cardiovascular diseases (CVD) for a long time remains extremely important, and, therefore, there are many works that offer new ways to diagnose and treat this group of diseases. Great opportunities are provided by the study of molecular interactions for a more accurate understanding of the pathogenesis of cardiovascular pathology. Many studies have recently been devoted to finding potential markers of CVD risk with the aim of more accurate and early diagnosis. In this review we analyze the latest literature data dedicated to the role of heat shock protein 70 (HSP70) in cardiovascular pathology. HSP70 take part in such processes as arterial hypertension, coronary heart disease, and atherosclerosis. In atherogenesis, serum heat shock proteins 70 play a major role. It has been proven that in patients with a high concentration of heat shock protein molecules circulating in the blood, increased values of the carotid intima-media complex were observed. The important role of antibodies to circulating HSP70 is noted. Found an association of high levels of these antibodies with atherosclerosis in patients with arterial hypertension in history, with myocardial infarction. Low levels of anti-HSP70 antibodies are observed in patients with acute coronary syndrome. This proves the complexity of the mechanism and the dual role of antibodies against serum heat shock proteins 70. Thus, antibodies against heat shock proteins 70 can be assessed as a protective marker, and as a predictor, which requires further study, and the HSP70 molecules themselves can somehow to participate in the development of cardiovascular pathologies. Much attention is paid to the role of the inflammatory process and the mechanisms of innate immunity in CVD. As it is currently believed that Danger-associated molecular patterns (DAMPs) are involved in the pathogenesis of these pathologies in the context of a “hazard/damage” model. According to this model, the triggering factor is stress, leading to the release of DAMPs and their binding to innate immunity receptors - Toll-like receptors (TLRs). Activation of TLRs triggers the signaling cascade in the cell leading to the synthesis of pro-inflammatory cytokines. This contributes to the development of inflammation, which can provoke the emergence of new pathological processes in the body and worsen the course of existing diseases. The identification of new potential markers and knowledge of the molecular mechanisms of the pathogenesis of CVD can play an important role in the development of a new individual approach to the prevention of cardiovascular diseases.

The present review article summarizes the latest world scientific data on the role of receptors for immune mediators in regulating biological effects on the cells. For the main classes of immune regulators (interleukins, interferons, growth factors and tumor necrosis factors), the variants are presented for participation of receptors as components of cytokine/cell interaction, as proven by in vitro and in vivo studies. Ability of the receptors expression to modify characteristics and type of these interactions is shown. The data on participation of receptors for regulatory molecules in development of immune-mediated diseases of various genesis have been analyzed. It was demonstrated that the changes in the receptor expression are of great importance when evaluating functional response of the cells to the mediators and in development of pathological conditions. Current studies confirmed the data suggesting effects of receptor density upon the processes of proliferation and apoptosis, as well as metabolic processes that trigger development of autoimmune, oncological and dystrophic diseases. For all the considered classes of regulatory molecules, the change in the density of receptor expression is one of the key aspects in regulating functional activity of the cells. Thus, studying expression levels of receptors on the cell membrane is important in understanding pathogenesis, whereas changing expression level may be considered as a therapeutic target in the treatment of various diseases.

To date, cancer diseases are one of the leading causes of mortality and morbidity in the world. Recent advances in understanding the molecular genetic mechanisms of oncogenesis and anti-cancer immune responses open new opportunities for the development of novel effective therapeutic strategies against cancer diseases; the strategies that would be more specific to tumor cells and less toxic to the host. Immunotherapeutic anti-cancer vaccines and oncolytic viruses are among the most promising approaches of this kind. For rapid and reliable screening and preclinical testing of new therapeutic approaches the relevant animal models are of critical importance. Such models provide the ability to partially reproduce tumor microenvironment and vascularization, as well as to reproduce at some extent the immune system reactions. Allograft and xenograft tumor models are the most common in cancer research. Allogenic transplantation involves the cancer cells or tumor fragments transfer between the organisms of the same species. Xenoplastic transplantation involves the transfer of tumor cells or tissues between the organisms of distinct species. Both tumor cell lines and patient-derived tumor cells and fragments obtained with biopsy can be used for xenotransplantation. Over the past decades the researchers developed numerous strains of immunodeficient mice and rats, suitable for xenografting human tumors. However, despite the widespread of immunodeficient laboratory animals as in vivo models in experimental oncology, these models do also have significant limitations associated with inability to fairly reproduce the tumor microenvironment and human immune system functions in mice, and also with the development of graft versus host reactions. Thus, when planning the experiments, it is necessary to carefully analyze all the advantages and disadvantages of animal strains, supposed to be used in experimental oncology studies.

The effects DNA methylation modulators on  pro- and anti-inflammatory cytokine production by fibroblast-like synoviocytes (FLS) were evaluated using FLS obtained from synovial tissues of 8 patients with active RA and cultivated for 3-7 passages in vitro.

It was shown that fenofibrate did not change levels of 5-methylcytosine (5-MeC) in FLS,  genistein and ademetionine increased 5-MeC concentrations  by 35%, and hydralazine resulted in twofold decrease of 5-MeC levels.

There was a spontaneous production of IL-6, IL-17, IL- 18, and IL-10 by FLS cultures, an addition of IL-1β to cultures resulted in significant up-regulation of these cytokines synthesis. DNA methylation donors decreased IL-6 production by FLS. In contrast with hydralazine and genistein, ademetionine decreased IL-6 production by FLS.  Synthesis of IL-17 was down-regulated with the addition of DNA-methylation modulators in low doses while there was no effect on IL-10 production. In conclusion, the effects of DNA-methylation modulators on production of pro- and anti-inflammatory cytokines by FLS is not only due to their impact on DNA methylation, but may be linked to other epigenetic mechanisms. FSC cultures may be used as a tool for preclinical assessment of new DNA methylation modulators.

Pancreatitis ranks third in the structure of acute surgical diseases of the abdominal cavity. The development of this pathology during pregnancy is complicated by premature birth in 58% of cases, which directly affects the indicators of perinatal morbidity and mortality.

Objective: to study the features of cytokine synthesis and their impact on the state of the fetoplacental system in acute pancreatitis in pregnant women, as well as to evaluate the effectiveness of the developed complex of therapeutic measures for the correction of violations and prevention of complications of gestation.

Material and methods. The study included 127 pregnant women with acute pancreatitis. The main group consisted of 43 pregnant women, who were additionally included in the complex of therapeutic and preventive measures: discrete plasmapheresis for 1 and 3 days and micronized progesterone (patent for the invention № 2535108 from 08.10.2014). In the comparison group (n=84), standard therapy of acute pancreatitis was performed. The control group (n=30) was represented by healthy pregnant women. The examination was carried out in accordance with the standards, the content of cytokines (interleukins IL-1β, IL-4, interferon IFN-γ, tumor necrosis factor TNF-α), the marker of apoptosis of Fas-ligand, hemodynamic parameters in the uterine arteries, the concentration of trophoblastic beta-1-glycoprotein (TBG) and placentospecific alpha-1-microglobulin (PAMG-1) in serum were additionally studied blood pregnant.

Research result. The combination of pregnancy with acute pancreatitis revealed increased levels of IFN-γ – 2.5-fold, IL-1β – 2.1 times, TNF-α – 2.5 times, IL-4 – 1.3 times in comparison with control data on the background of decrease in Fas-L – in 1,3 times and increase of indexes of peripheral resistance in the uterine artery in 1.3-1.4 times, which was accompanied by the exclusion of gravidarum synthesis of proteins: a decrease in TBG (1.3 times) and increase of PAMG-1 (1.9 times). Dynamic control of the studied parameters showed the preservation of high concentrations of cytokines and progression of uterine hemodynamic disorders in the standard treatment of the disease, which led to the appearance of signs of threatening termination of pregnancy on 7-10 days in 83.3% of women. In addition, the development of pancreatitis at different gestation periods increases the risk of spontaneous miscarriage to 11.9%, non – developing pregnancy – up to 29.8%, premature birth-up to 60.7%, as a result of the formation of chronic (78.9%) and acute (21.1%) placental insufficiency. The additional use of discrete plasmapheresis and progesterone drugs helped to restore the balance of Pro-and anti-inflammatory cytokines by the 3rd day of treatment, preventing their long-term negative impact on the structure and function of the utero-placental complex.

Conclusion. The combination of pregnancy with acute pancreatitis is accompanied by dissociation of the immune response with predominance of Th1-cytokines against the background of apoptosis oppression and placental dysfunction development. The use of the developed method of complex treatment allows to reduce the frequency of threatening termination of pregnancy with the development of acute pancreatitis – 3 times, reduce the number of premature births – 13 times, and reduce pregnancy losses to zero.

    The level of expression of genes of transcription factors (GATA-3, TBX21, IL-2PG), and changing  of oxidative processes in ischemic stroke were studied.

It was found that activation of Th2 cells (increase in the expression of transcription factor GATA-3) is observed in stroke,   and suppression of Th1 cells (a decrease in the expression of IL-2 and its receptors, as well as the TBX21 gene).  Increasing the expression of transcription factor GATA-3 in stroke patients underlies the increase in production in these patients of Th2-cytokines.    

A comparative analysis of protein oxidation in blood plasma revealed an increase in the intensity of oxidative modification of proteins in stroke patients.

  Investigation of glutathione content, activity of glutathione peroxidase enzymes, glutathione reductase in erythrocytes in stroke revealed a decrease in the content of glutathione and glutathione reductase and an increase in the activity of glutathione peroxidase.

The findings may be useful for a better understanding of the mechanisms of stroke.

At present, at least two phenotypically different subpopulations of blood monocytes have been identified: "classical" monocytes with the phenotype CD14⁺⁺/CD16^-  and "nonclassical" (pro-inflammatory) with the phenotype CD14⁺/CD16⁺. It has been established that monocytes CD14⁺/CD16⁺  participate in latent or so-called systemic non-infectious inflammation in the human body along with blood neutrophils and microglial cells of the brain, which are the analogue of monocyte/macrophage system in the brain. Monocyte function disorders are considered as one of the links in the neurodegenerative process underlying the neuroinflammatory hypothesis of the development of schizophrenia. In this connection, the aim of this research was to study in patients with juvenile depression the amount of pro-inflammatory monocytes in terms of the expression level of CD14⁺/CD16⁺  receptors as well as the activity of leukocyte elastase and a1-proteinase of elastase inhibitor. It was also interesting to determine the mechanisms of their interaction in the pathogenesis of immunosuppression, in particular, to identify a possible connection of pro-inflammatory monocytes with the activity of leukocyte elastase and a1-proteinase of elastase inhibitor in patients with juvenile depression at the early stage of disease. 27 male patients aged 17-23 years were examined. The disease diagnostics was carried out in accordance with the criteria of ICD-10 according to which all patients have depression with the syndrome of attenuated psychotic symptoms (Attenuated Psychotic Syndrome) in the structure of psychopathological disorders. 12 mentally healthy age- and gender-matched persons were examined as controls. Monocytes were obtained by the conventional method of adhesion to the plastic surface from mononuclear cells isolated from peripheral venous blood of patients and healthy controls by centrifugation in a ficoll-urographin density gradient (ρ = 1.077). In the blood of patients and healthy controls, the level of monocytes with the phenotype CD14⁺/CD16⁺, the enzymatic activity of leukocyte elastase and the functional activity of α1-proteinase inhibitor were studied. The clinical and laboratory study showed an increase of more than twofold in the level of the pro-inflammatory subpopulation of CD14⁺/CD16⁺ monocytes in patients compared with its level in healthy individuals. The increase was accompanied by an elevation of leukocyte elastase and a1-proteinase inhibitor activity. A positive correlation was found between the increase of surface receptors CD14⁺/CD16⁺ expression on monocytes and elevation of the leukocyte elastase activity.

These results confirm participation of CD14⁺/CD16⁺ monocytes in the development of latent or non-infectious immune inflammation, and determine the mechanisms of possible interaction between monocytes and neutrophils in the development of immune inflammation  in patients with juvenile depressions with the Attenuated Psychotic Syndrome.

The diagnostic of tuberculosis infection, including the use of immunological methods, evolved significant changes. The introduction of new diagnostic tests allowed to improve the diagnosis of latent tuberculosis infection (LTI). However, the positive results of immunological tests in both tuberculosis patients and in those with LTI do not allow to divide these conditions, which requires the development and implementation of new diagnostic approaches.

Materials and methods. A prospective study with a survey of two groups of patients was conducted: group I (n=50) - patients with verified pulmonary tuberculosis, MBT (+); group II (n =15) – subjects with LTI and control group – healthy subjects (n=14). The examination complex included clinical, radiological, bacteriological, immunological (Mantoux test with 2 TU, T-SPOT.TB, QFT and Diaskintest) methods. Immune complexes were determined in all patients and healthy individuals by the method of dynamic light scattering after the in vitro addition of specific antigens - peptides ESAT-6 and SFP-10.

Results. The obtained data demonstrate the low informativeness of the clinical method in the diagnostic of pulmonary tuberculosis. In the presence of characteristic X-ray changes, bacteriological verification of tuberculosis was obtained only in 46% of cases. The use of various immunological tests allows to obtain positive test results in 84-90% of cases simultaneously with the 100% of the positive results in subjects with LTI. Determination of specific immune complexes by the method of dynamic light scattering allows to determine the activity of tuberculosis infection in 100 % of cases and to identify a high-risk group for the development of active tuberculosis in people with latent tuberculosis infection.

Conclusions: the obtained data can be applied not only in the diagnosis of active tuberculosis in the absence of diagnosis verification, but also allow to identify a high-risk group for the development of the disease in people with latent tuberculosis infection.

We have studied HLA allogeneic interactions in short-term cultures of lymphocytes from the parents having children with congenital heart defects (CHD), or subject to early reproductive losses. Twentyone married couples (CHD as the main group) who had children with sporadic CHD (interventricular septal defect) without chromosomal diseases were observed. Fifty married couples (a comparison group) had two or more reproductive losses in early gestation (up to 9 weeks), denoted as PNPs (miscarriages, missed abortions, habitual miscarriages. Forty-one families with three or more healthy children represented a control group. Immune response in cell cultures was evaluated by increasing expression of HLA-DR in a mixed culture, as compared to spontaneous lymphocyte cultures. Initial labeling of female and male lymphocytes with monoclonal antibodies to CD45 conjugated to different fluorescent dyes (PC-5 and PC-7) allowed us to evaluate the immune response of female lymphocytes to males and vice versa. The suppressor effect of autologous female serum upon the mixed culture of the lymphocytes of the spouses was also evaluated. Results of the present study showed a difference in HLA allogeneic interactions in the short-term culture of lymphocytes registered for spouses with reproductive losses and children with congenital heart defects. Reproductive losses were associated with a low blocking effect of female auto-serum upon allogeneic HLA interactions in the short-term culture of the lymphocytes of the spouses. Congenital heart defects were associated with high activity of female B-lymphocytes (CD3-/HL-DR+) in short-term mixed culture of lymphocytes from the spouses.

One of the urgent problems of modern medicine is the search for genetic markers of chronic obstructive pulmonary disease (COPD).The aim of the study was to investigate the relationship between HLA haplotypes and COPD in individuals whose illness developed during the professional work in the workshop of organic-silicon production of PJSC "Khimprom" (Novocheboksarsk, Russia).The study included patients with COPD in remission, belonging to the Chuvash ethnic group of Russia - 36 women and 26 men (mean age 45.4±2.3 years). The work experience averaged 15.2±2.4 years, the duration of COPD - 12.3±2.4 years. Smokers made up 22.0±5.8% of the total number of patients. The comparison group was a group of non-patients with COPD workers of organic-silicon manufacture. This group was positioned as "stable" to the development of  COPD. Class I HLA antigens were typed in the standard microlymphocytotoxic test using histotyping anti-HLA sera to 8 HLA-A antigens of the locus A1, A2, A3, A9, A10, A11, A19, A28 and  to 18 HLA-B antigens of  the locus  В5, В7, В8, В12, В13, В14, В15, В16, В17, В18, В21, В22, В27, В35, В40, В41, В42, В53) (CJSC “Interregional Center of Immunogenetics and Histotyping Reagents “Gisans”, St. Petersburg). HLA genotyping of class II alleles was carried out by the multi-primer polymerase chain reaction method in DNA, obtained from nuclear cells of peripheral blood, using reagent sets of the firm “DNA-Technology” (Moscow), according to the reagent manufacturer's method. They were typified by 14 alleles of the DRB1 locus, 8 to the DQA1 alleles and 11 to the DQB1 alleles. The frequencies of two-locus haplotypes were calculated using the computer program "Arlequin v. 3.01 ". The association strength of HLA with COPD was determined by the relative risk (RR) of the formula J. Haldane. The statistical reliability of the difference between RR and 1 was determined by the exact two-sided Fisher test. As a result of the study, the positive association of COPD with haplotypes was established: HLA-A9-DQA1*0501,  A10-DQA1*0103, A28-DQA1*0102,  B7-DQA1* 0103. These haplotypes can be attributed to genetic markers of predisposition to the development of COPD. The negative association with the disease was established for haplotypic combinations of the alleles HLA-A2-B8, A19-DQB1*0502-04, B12-DQB1*0502-04, B27-DQA1*0103, DRB1*01-DQA1*0101, DRB1*07-DQA1*0201, DRB1*13-DQA1 * 0102. This series of haplotypes can be attributed to the category of protective genetic markers of COPD in conditions of organic-silicon manufacture. In continuation of our studies, further research is needed to identify "marker" HLA haplotypes in COPD in other ethnic populations, as well as under the influence of other aggressive air pollutants. The results of the study indicate the association of COPD with a number of specific HLA-haplotypes.

A large and diverse repertoire of antibodies encodes the history of past immunological experience, creating a global network of the body’s regulation system. In this article, we propose to use a peptide microarray (“immunosignature”) for evaluating global individual antibody patterns and bioinformatic data analysis for differential diagnosis of autism spectrum disorders. The peptide microarray consists of 124 000 antigen mimetics with random sequences covalently bound to the surface of the glass slide. A drop of plasma is tested for the presence of antibodies of distinct specificity, by measuring their binding to each antigen mimetic in the microarray detectable by fluorescent staining with secondary IgG antibodies, and this reaction is registered by laser activation assay. For bioinformatic analysis, we used the files of digitalized fluorescence intensity data, which presented the reactivity of plasma antibodies bound to antigen mimetics. Data processing was carried out by packages of the Bioconductor project for the R software environment to perform statistical evaluation. At the stage of primary data processing, the quantile normalization was used in order to equalize the distributions of antibodies’ reactivity. The sample data and other necessary information were combined into the discrete ExpessionSet container files. To compare the control and experimental groups, the Welch’s one-way ANOVA (for unequal variances) was used. The obtained estimates of the mean value differences and statistical significance of P levels were used further for constructing a volcano diagram, in order of ranking and selecting the most promising antibody reactivity parameters.
For differential diagnosis of autism, and evaluation of diagnostic significance of the immunosignature method, a heatmap was constructed. The standardized values of the logarithms of antibody reactivity, and the results of the hierarchical cluster analysis performed by the Ward method using Pearson correlation, as a measure of similarity were used in constructing the heatmap. As a result of the bioinformatiс analysis of the data, 73 antibodies were selected whose reactivity had statistically significant differences in groups of children with autism and normally developing children. These antibodies were used for differential diagnosis, the value of which was determined in the heatmap construction. It was found that the group of children with autism spectrum disorders by the antibody reactivity exhibits marked heterogeneity, and consists of at least two subgroups. In addition, 60 antibodies in children with autism showed predominantly medium and low reactivity, i.e. these antibodies had a weak binding power with antigenic mimetics, and only 13 antibodies showed high reactivity. In general, diagnostic specificity of the autism spectrum disorders using immunosignature approach was 96.0% (95% CI 82.8 to 99.6%), sensitivity was 78.3% (95% CI 64.9 to 88.2%), and diagnostic efficiency was 82.7%. Our pilot study allows us to propose a method of immunosignature for differential diagnosis of autism and, possibly, to expand our understanding of autism spectrum disorders.

There are some data about various immunopathology effects of food dyes. Their use in food and medicines may induce hypersensitivity, which is regarded as a side effect of drugs or intolerance to food substances. Evaluation of the effect caused by food and drugs colorants on the immunity was conducted in 68 patients with chronic allergic diseases without the exacerbation and 23 healthy individuals. The provocative oral test was supplied with 2 mg of titanium dioxide (TiO₂) in powder or 2 mg of tartrazine in wheat flour processed at a cooking temperature or in a gelatin capsule containing 0.2 mg of titanium dioxide. The oral fluid and/or venous blood were taken up on an empty stomach and 40 minutes after the test. The peroxidase activity of oral fluid and the expression of CD203c and IgE markers on blood basophils were studied. The blood of 20 patients with allergopathology was incubated for 3 and 24 hours with 0.001% and 0.01% mixture of tartrazine, carmoazine, ponso, sanset, TiO₂ solutions with the determination interleukin 17 (IL17) level in the supernatants. Peroxidase activity of oral fluid increased on 30% or more in 30% of cases after tartrazine and wheat flour provocation in patients with allergies (12.5% in healthy persons), 44% - after TiO₂ in patients with allergies (22% of cases in healthy individuals), 63% - after tartrazine and TiO₂ in the white gelatin capsule in patients with allergies (in healthy individuals, p = 0.047). The number of IgE⁺CD203c⁺ basophils increased in 44% cases and decreased in 50% cases after provocation with TiO₂ in the group of allergic patients, compared with 22% increasing and 22% decreasing in healthy (p = 0.007). A lower concentration of the dye mixture (0.001%) induced IL17 secretion in the supernatant in all 20 patients with allergic diseases, the maximum permissible concentration (0.01%) of the dyes solution - less often in 40% of the examined (p = 0.0002). Secretion of IL17 under the influence of the both concentrations was higher than in the control samples (p <0.05). Thus, the dyes of food and drugs show immunomodulatory activity in patients with allergic diseases (more often) and in healthy individuals. The connection of a positive provocation test with food dyes tartrazine and titanium dioxide with oral fluid peroxidase activity increasing and the number of IgE⁺CD203c⁺ basophils and IgE^bright basophils increasing and IL17 secretion under the influence of these dyes was found.

The paper presents the results of the study of the effectiveness and safety of the use of systemic enzyme therapy with Wobenzym in the complex treatment of patients with hormone-dependent severe bronchial asthma. It was found that the inclusion in the complex basic therapy of severe hormone-dependent bronchial asthma systemic enzyme Wobenzyme accompanied by improving the parameters of the functional state of the bronchi, reducing circulating immune complexes, a steady increase in cortisol levels. The data obtained convince of the safety of the inclusion of the preparation of systemic enzyme therapy in the complex treatment of patients with severe hormone-dependent bronchial asthma, improving the effectiveness of basic therapy, improving control over the course of the disease, allow to develop indications for the appointment of Wobenzyme patients with severe bronchial asthma.

Rheumatoid arthritis (RA) is a most common autoimmune inflammatory arthritis in adults. Serological marker of RA are rheumatoid factor (RF) and antibodies to cyclic citrullinated peptide (ACCP). The main genetic factor that determine predisposition to RA is HLA-DRB1 alleles. The HLA-DRB1 locus alleles may encode a common 5-amino acid sequence called ‘shared epitope’ (SE).
The aim of our study is to assess the clinical significance and occurrence of SE and HLA-DRB1 genes and to analyze the prognostic significance of these factors for RA patients.
We collected a serum and DNA samples from 72 patients with RA. For genotyping of HLA-DRB1 locus “DNA-Technology” kits (Moscow, Russia) were used. HLA-DRB1 SE sequences were genotyped by real-time PCR with specific primers. Determination of ACCP in serum was performed by ELISA (Euroimmun AG, Lübeck, Germany), RF detection, by turbidimetric method. Clinical status of the disease was assessed using the RA DAS-28 Activity Index.
We have obtained the following results: determination of HLA-DRB1 gene frequency in the North-West region of Russia showed that the HLA-DRB1*04 gene variant occurred at 11.4%, HLA-DRB1*01, 14.2%. HLA-DRB1*10 and HLA- DRB1*14 occured, respectively, in 0,8% and 2% of the cases. The DRB1*04 and DRB1*01 allelic variants were found in 73.6% of patients with RA, and in 43.9% of the control group. Among patients with RA, the SE gene frequency was 66.6%. SE is associated with ACCP detection and higher DAS28 index. Conclusions: The allelic variations of HLA-DRB encoding SE are associated with ACCP-positive RA in the population of the North-West region of the Russian Federation. Identification of HLA-DRB1 allelic gene variants and SE sequences in this locus serve as an additional test to specify serological diagnosis in rheumatoid arthritis.

We performed clinical observations and laboratory examination of 22 patients with chronic pyelonephritis (chronic renal failure, CRF) and 30 healthy individuals. The patients with CRF were examined twice. The first group (Group I) included patients with exacerbation of the disease. The comparison series (Group II) was represented by the same patients who were examined 1.5-3 months after completion of treatment, without clinical exacerbation of chronic pyelonephritis (CPN). Laboratory signs of acute renal damage were not detectable in all the patients examined. Concentrations of VEGF, MCP-1, IL-8 and IL-18 were determined in urine samples of all examined persons by ELISA technique. Protein spectrum of urine was assessed in six patients from Group I, and in six cases of Group II by means of mass spectrometry, using Agilent 1100 chromatographic device, and LTQ-FT Ultra hybrid mass spectrometer. The results of parallel determination of urine proteins by the two methods have shown that the evolving CPN exacerbation is associated with local secondary immune deficiency at the level of renal tubular urothelium. Determination of urine proteome by means of mass spectrometry in exacerbating disease allows identify the proteins associated with damage to epithelial lining of renal tubules and development of local immune response.

Objective of study: refining immune diagnostics of systemic scleroderma through determining ceruloplasmin antibodies, its amount and enzymatic activity, as well as control of effectiveness of therapy with ceruloplasmin-based immobilized magnetocontrollable immunosorbents.

Materials and methods. 30 apparently healthy individuals and 68 patients with systemic scleroderma were examined. The study included patients with referral diagnosis of systemic scleroderma who signed an informed consent. The study was performed in accordance with the principles of World Medical Association Declaration of Helsinki rev. 2013 (ACR/EULAR). All participants had their blood tested with the method of immunoenzymatic determination of antibodies to ceruloplasmin upon admission to hospital and prior to discharge.Results. It was established that patients with systemic scleroderma show reduced oxidase activity of ceruloplasmin, increased ceruloplasmin levels, as well as elevated antibodies to ceruloplasmin compared with the control group. A link between the amount of antibodies to the studied enzyme, and the activity, nature, course and stage of the disease was established. It was found that there is a reliable negative correlation between the level of ceruloplasmin antibodies, and the amount of RBCs, the hemoglobin level. For the first time a complex assessment of three parameters was employed, the parameters being the enzymatic activity, ceruloplasmin amount, and antibodies to ceruloplasmin. It was established that autoantibodies to ceruloplasmin are more often found in systemic scleroderma patients who show a high disease activity, subacute course with involvement of the liver, lungs, and with anemia. It was found that antibodies to ceruloplasmin are detected at early stages of systemic scleroderma development and can be used in timely diagnosis of the condition. It was shown that the change of parameters under study over time can serve as a basis on which to evaluate the effectiveness of administered therapy.

Conclusion. Decreased enzymatic activity of ceruloplasmin, its elevated amount and increased antibodies to ceruloplasmin can be taken as additional diagnostic tools in evaluation of systemic scleroderma activity. These parameters promote a more accurate assessment of the disease activity and of the nature of the pathologic process; they can serve as an indication of a variety of clinical forms of the disease. Employing these parameters for monitoring of administered therapy in hospital settings permits a more accurate assessment of its effectiveness and making adjustments. Studying ceruloplasmin antibody formation, amount of ceruloplasmin and its biochemical activity extends the existing concept of rheumatic disease pathogeny, outlines a way forward for further research and reflects the involvement of antioxidant system in immune disorders.