Abstract. Incidence of allergic diseases is increased over last years. House dust is considered a major risk factor of allergic sensitization which plays an important role in development of allergic rhinitis, bronchial asthma, atopic dermatitis. Dust mites in the home comprise a large part of domestic allergens. Dermatophagoides pteronyssinus, Dermatophagoides farinae, Euroglyphus maynei, Lepidoglyphus destructor, Blomia tropicalis are most important in this respect. Der p 1 and Der p 2 are regarded as major house dust mite allergens. Recent studies concerned induction of IgE responses against mite tropomyosin (Der p 10), an allergen occurring in mites which exhibits high cross-reactivity with tropomyosins from a variety of sea foods (e.g. shrimps), as well as human tropomyosins. Allergen-specific immunotherapy (ASIT) represents the only causative approach to allergy treatment in such cases. From this viewpoint, a quantitation of specific IgЕ against major house dust mite allergens would be necessary to predict ASIT efficiency. Treatment by house dust mites allergen extracts is effective in management of allergic rhinitis and mild asthma. A component-resolved diagnostic (CRD) with purified house-dust mites allergens allows to discriminate patients who were mostly sensitized to the major house dust mites allergens (e.g. Der p 10, tropomyosin). The component-resolved diagnostics could be performed before starting the allergen-specific immunotherapy by mite allergens, in order to avoid unresponsiveness to this mode of therapy.

Abstract. Expression characteristics of transcription factor PAX-5 (paired box 5) are considered for different clinical variants of bronchial asthma (BA). Low levels of PAX-5 expression may be a reason for progression into a severe allergic asthma, whereas higher levels of PAX-5 expression may represent a significant factor leading to development of non-allergic bronchial asthma. Initiation of IgE production is supposed to be a less important PAX-5 function in BA pathogenesis, than prevention of B-cell-to-plasmocyte differentiation. Further investigations of PAX-5 properties and its co-operations with other transcription factors may provide a promising path in further research of BA pathogenesis.

Abstract. We have observed thirty-six patients with coronary artery disease (CAD) who have undergone coronary artery bypass graft (CABG) surgery. In patients with uncomplicated clinical course post-CABG, total lymphocyte counts, T-, B- and NK-cell contents did not significantly differ from baseline levels. Meanwhile, the numbers of CD14HIGH and CD14LOW monocyte subpopulations showed significant differences from initial levels at day 1 and day 7 after surgery. The changes in monocyte subsets in blood of patients with and absence of post-surgical septic complications reflected severity of inflammatory response, and development of systemic inflammatory syndrome. In such a case, further studies of peripheral blood monocytes can be both a useful tool for studying the mechanisms of systemic inflammation, as well as a good diagnostic system, in order to assess the patient’s condition and to predict post-surgical clinical outcomes.

Abstract. We have studied cellular immune state in patients with progressive fibrous cavernous tuberculosis (FCT) with varying severity of lung destructive changes. It was found that increasing number of specific cytotoxic lymphocytes, NK-, NKT-, CD95-cells and activated T-lymphocytes, accompanied by a significant decrease of T-helper cells, B cells, CD25-cells, is a sign of destruction, along with inhibition of antigen-specific cellular response and functional insufficiency of T-helper and cytotoxic lymphocytes. Increased severity of the disease is consistent with activation of B cell compartment and weaker phagocytic function of neutrophils.

Significant differences were revealed in spontaneous and induced production of IFNγ, IL-2 and IL-8 between various groups of patients with FCT. The alterations of immune and cytokine status in a certain clinical subgroup with progressing FCT were indicative for depletion of immune system potential. As based on these data, we have established some criteria in order to assess severity of immune pathology in the patients with progressing FCT which may be of predictive value for evaluating trends in development of the specific process and feasibility of immune correction therapy.

Abstract. Multiple parameters of immune system were studied in patients with various clinical forms of tickborne encephalitis (TBE). The patients were examined in acute phase of the infection. It is shown that early immunopathogenesis of TBE, in its feverish form, corresponds to general immunological mechanisms of viral infection. Meanwhile, in focal clinical forms of TBE with favorable outcome, we revealed a deficiency of T-cell immunity, disimmunoglobulinemia, and low Th1-cytokine production. In a focal form with fatal outcome, an early hyperproduction of Th1-cytokines and complement components, as well as increased numbers of activated T-lymphocytes have been noted, along with reduced levels of cytotoxic lymphocytes. The changes observed may be considered as early prognostic criteria of a severe infection.

Abstract. A group of 266 patients with spondyloarthritidis and 69 healthy persons were included in our study. IgG preparations were isolated from blood sera by a combined rivanol/affine chromatography technique. Homogeneity of IgGs was tested by means of SDS-PAGE. Serum samples from patients and healthy persons, and IgG subclasses 1, 2 and 4 were tested for DNAse activity. A method of DNAse activity measurement was based on rivanol capacity to form a clot with DNA. We have found highly significant differences between the levels of DNAse activity associated with IgG preparations and in blood sera from patients with spondyloarthritidis, and healthy donors (p < 0,0001). DNAse activity of IgG and sera in patients with psoriatic arthritis was higher than in patients with reactive arthritis and ankylosing spondylitis (p < 0,0001). Multiple correlations were revealed between DNAse activity of IgG, blood serum, clinical signs of psoriatic arthritis, reactive arthritis, ankylosing spondylitis, and laboratory findings. We have developed novel tests for differential diagnosis between various disorders, e.g., spondyloarthritidis, based on IgG and serum-associated DNAse activity, corresponding to the criteris of useful and very useful diagnostic tests in rheumatology.

Abstract. Pathogenesis of acute post-streptococcal glomerulonephritis (APSGN), a major complication of group A streptococcal (GAS) throat or skin disease, remains unclear. Over years, various theories were based on distinct streptococcal extracellular factors, as well as immunological mimicry of streptococci for renal tissue antigens was considered. Previously we reported that a lot of clinical GAS isolates with proven nephritogenic ability show a non-immune binding of monomeric or aggregated IgG. Moreover, using a rabbit model of APSGN, we obtained evidence for important causative role of streptococcal IgG Fc-binding proteins (IgG FcBPs) belonging to the M family surface proteins. I.e., rabbits injected by whole IgG FcBP-positive streptococci showed induction of renal glomerular changes, with deposition of IgG and complement C3, resembling the picture recorded in human APSGN. These typical renal changes were always preceded by development of circulating anti-IgG antibodies. Present study was performed in the same rabbit model. Both purified IgG FcBPs isolated from type M22 GAS were found to elicit glomerular degenerative damage of renal glomeruli comparable to those caused by whole bacteria, as well as induce anti-IgG antibodies, deposition of IgG and C3 complement and production of proinflammatory cytokines (IL-1β, TNFα, IL-6) by glomerular mesangial and endothelial cells. By contrast, rabbits injected with proteins A or G, IgG FcBPs of S. aureus and group G streptococci, respectively, exhibited only low levels of circulating anti-IgG and reversible glomerular changes. In these settings, we have not observed any features of membranousproliferative glomerulonephritis (GN) resembling morphological traits of acute post-streptococcal GN in humans. These data correlated with results obtained after injection of intact Staphylococcus aureus (Cowan 1 strain) or group G streptococci (G148 strain). Both microbial types are known to harbor IgG Fc-binding proteins (А and G, respectively). These results support the idea that GAS IgG FcBPs are unique in their ability to initiate strong post-streptococcal glomerular changes and could be considered as important factors in pathogenesis of APSGN similar to acute post-streptococcal GN in humans.

Abstract. An intracellular staining technique of marker cytokines was applied for evaluation of quantitative distribution of T-lymphocyte effector subsets in children and adults. The results of this study have shown that the numbers of Th2 lymphocytes in infants (7 to 12 months old) correspond to appropriate normal values in adults, being accompanied by decreased Th1 and Тс1cell contents, whereas absolute amounts of Tc2 lymphocytes proved to be higher than in all other age groups. Absolute counts of Th17 and Tnc17 subsets in infants of 7 to 12 months were higher than in adults. Hence, these infants exhibited a shift of immune response towards Th2 (Tc2) and Th17 (Tnc17), thus presenting a potential factor of Th2-mediated allergic disorders in the children under one year. In children over 1 year, absolute amounts of Th1 and Тс1, as well as Th2 and Тс2 lymphocyte counts did not significantly differ from adult values. Th2 lymphocyte counts among adolescents (15 to 18 years) were decreased, along with relative increase of IL-17А-positive lymphocyte scores, thus reflecting a probable predisposition for autoimmune disorders induced at this age. The age-dependent increase in Th1 and Тс1 counts in children may immediately correlate with formation of T-cell memory pool.

Abstract. Time dynamics of CD14 and СD16 antigen expression on the surface of peripheral blood monocytes and serum cytokine contents was evaluated at different terms after surgical intervention in patients undergoing on-pump coronary artery bypass graft surgery. An association has been shown between severity of organ dysfunctions, as assessed by SOFA scores, and concentrations of IL-6 and IL-10 during early postoperative terms. On day +1 after surgery, the monocyte subpopulation profile was changed, due to relative decrease in CD14hiCD16– and increase in CD14hiCD16+. Expression of CD14 on the surface of CD14hiCD16–is reduced, along with increased expression of CD16 receptor. The observed association between relative CD14hiCD16– contents, CD16 expression level on CD14hiCD16+ monocyte subpopulation, and SOFA scores suggest a significant contribution of above-mentioned subpopulations to clinical course at early terms after surgical intervention.

Abstract. Present study defines clinical, hormonal and immunological factors allowing to predict outcomes of IVF cycles in patients with combined forms of infertility at their reproductive age. Indices of gonadotrophic ovarian stimulation in IVF cycles in patients of reproductive age with combined forms of infertility depend on their age and cytokine contents in follicular fluid. Effectiveness of gonadotropin-induced ovarian stimulation is inversely dependent on the patients’ age, its increase is related to increased contents of pro-inflammatory cytokines in follicular fluid and increased expression of CCR1, along with decreased expression of CCR3 chemokine receptors in endometrium. Effectiveness of gonadotropin-induced ovarian stimulation depends on concentration of cytokines in the follicular fluid, which is argued by presence of a significant direct correlation between the number of growing follicles, oocytes and local contents of IL-10, IL-15, eotaxin, MIP-1β, RANTES, TNFα, IFNγ, and GMCSF. Free testosterone levels show a positive correlation with numbers of oocytes obtained from the ovarian punctate, and CXCR2 and CCR3 expression in endometrium, as well as a negative correlation was found with IL-4 contents in follicular fluid. In patients with negative IVF cycle outcomes, levels of IL-13 in follicular fluid upon ovarian stimulation proved to be twofold higher than those in patients with successful pregnancy after IVF. Prognosis for pregnancy in a cycle of treatment in patients with combined forms of infertility of reproductive age is determined by a patients’ story, and a variety of clinical, hormonal and embryological factors which can increase predictive accuracy of the IVF outcomes. To determine a probability of successful pregnancy after IVF cycle, an appropriate prognostic index is recommended, with a sensitivity levels of 93% and specificity of 89%.

Abstract. The aim of this study was to evaluate some immunopathogenic features of autoimmune thyropathies (autoimmune thyroiditis and Graves’ disease), in terms of IL-2 and IL-4 production and expression of specific surface receptors on blood lymphocytes. We have revealed some relationships and peculiarities of the immune state deviations in these clinical disorders. We evaluated interrelations between some indexes of IL-2 and IL-4 production/reception, and functional parameters of thyroid gland in the patients. Multi-directional effects of interleukin-2 upon thyroid function were revealed, e.g., reduced cell proliferation levels and decreased functional activity of thyrocytes in autoimmune Hashimoto’s thyroiditis, as well as stimulation of proliferation and hormone production by thyrocytes in Graves’ disease.

Abstract. The study included 154 cases of acute myocardial infarction (MI) with ST segment elevation. Cytokine levels were determined in all the patients at days +1 and +10 after hospital admission, using quantitative ELISA assays. On day +1, a more that 2-fold increase was revealed for TNFα and IL-1α, as compared with healthy individuals. On day +10, we found a more than twofold increase in TNFα and IL-8 in blood plasma, whereas IL-1α and IL-10 levels became significantly reduced by the day +10, as compared to median values at day +1 of the study. Moreover, dynamics of the cytokines was compared between clinical subgroups of MI patients classified by gender, age, or presence of early complications. It was noted that the patients with complicated course of myocardial infarction exhibited high levels of IL-1α both on the day 1, and on day +10 of the disease. In female patients, the levels of both IL-8 and IL-10 were not significantly changed by day +10 after MI. Among younger patients (<56 years old), a significant reduction of IL-10 plasma levels was shown by day +10 of myocardial infarction, as compared with absence of significant IL-10 dynamics in older patients.

Abstract. This study demonstrates ability of carbon monoxide to trigger mitochondrial pathway of apoptosis induction of Jurcat cells. We have shown that proapoptotic action of carbon monoxide is coupled to permeabilization of cellular mitochondrial membranes. Imbalance in Bcl-2 family of regulatory proteins may be considered among possible reasons of the membrane pore formation. We have shown downregulated cl-2 and Bcl-xl mRNA expression and decreased levels of antiapoptotic proteins, along wih decreased mRNA expression and increase of Bad proapototic protein level in Jurkat cells following incubation with 50 μm of CORM-2, a carbon monoxide donor.

Abstract. Placental cell populations produce a great variety of angiogenic factors and cytokines than control angiogenesis in placenta. Functional regulation of endothelial cells proceeds via modulation of endothelial cell receptors for endogenous angiogenic and apoptotic signals. Endothelial phenotype alteration during normal pregnancy and in cases of preclampsia is not well understood. The goal of this investigation was to evaluate altered expression of angiogenic and cytokine receptors at EA.hy926 endothelial cells under the influence of placental tissue supernatants. Normal placental tissue supernatants from 1st and 3rd trimesters, and pre-eclamptic placental tissue supernatants (3rd trimester) stimulated angiogenic and cytokine receptors expression by the cultured endothelial cells, as compared with their background expression. Tissue supernatants from placental samples of 3rd trimester caused a decreased expression of angiogenic and cytokine receptors by endothelial cells, thus reflecting maturation of placental vascular system at these terms. Supernatants from preeclamptic placental tissue induced an increase of CD119 expression, in comparison with normal placental supernatants from the 3rd trimester. This finding suggests that IFNγ may be a factor of endothelial activation in pre-eclampsia. The study was supported by grants ГК №02.740.11.0711, НШ-3594.2010.7., and МД-150.2011.7.

Abstract. Age dynamics of humoral immunity was studied in healthy children, i.e., 11 newborns, 33 infants of 4 to 8 months, 32 children of 1 to 2 years old,, 17 children of 4 to 5 years old, 25 children of 6 to 8 years old, 15 children of 9 to 11 years old, and 28 adolescents of 14 to 16 years old. Evaluation of membrane receptors on B cells was performed by means of three-colour fluorescent label and allowed of characterizing B1 subpopulations (CD19+CD5+CD27-), naпve B2 cells (CD19+CD5-CD27-), and B2 memory cells (CD19+CD5-CD27+). B1 cells have been shown to dominate in blood of newborns and younger children (up to 5 years old). By the contrary, B2 memory cells were nearly undetectable in newborns, and exceeded 20% in adolescents (by 15 years old). Meanwhile, it has been revealed that the amounts of IgG1 and IgG3 subclasses did progressively increase with age, whereas IgG2 remained decreased to 50% of adult values for a long time, and reached them by 11 years and later. We suggest that the age dynamics of IgG subclasses is connected with age-dependent changes in B cell subpopulations.

Abstract. Employing an in vitro cellular system, we have studied effects of estriol at physiological concentrations corresponding to the 1st, 2nd , and 3rd trimesters of pregnancy upon phagocytic, bactericidal activity of monocytes, and their ability to form extracellular traps. This steroid hormone does not significantly affect phagocytic function of monocytes at concentrations corresponding to the 1st, 2nd , and 3rd trimesters of pregnancy, however, leads to increased formation of extracellular traps and increase of oxygen-dependent bactericidal effects.

Abstract. We have observed eighty-nine patients with chronic recurrent infections of upper respiratory tract. Multiple immune parameters were evaluated during remissions of the disease. Increase in relative and absolute CD3+CD4+CD25+, CD3+HLA-DR+, CD3+CD16/CD56+ counts of blood lymphocytes, as well as higher concentrations of circulating immune complexes (CIC), along with decreased serum IgM and IgG levels were observed among the patients, as compared with appropriate parameters of control group. However, the major lymphocyte subsets did not differ between patients and controls. Hence, a content of CD3+CD16/CD56+ lymphocytes proved to be the most informative immunological parameter in the patients, since their levels directly correlate with duration of the disease and exacerbation rates. Meanwhile, CD3+СD16/СD56+cell counts show a negative correlation with the total numbers of B-lymphocytes and IgM concentrations in peripheral blood.

Abstract. Clinical course and outcomes in chronic hepatitis C (CHC) depend on the state of cellular immunity in the patients. We have analyzed some indexes bearing on absolute and relative contents of NK-cells (CD3-CD16+CD56+), and their activated forms (CD3-CD16+CD56+CD107+a), as estimated by the LAMP-protein (CD107a) expression in peripheral blood of seventy patients with verified diagnosis of CHC. A significant reduction in cytotoxic potential of NK cells was revealed in patients with chronic hepatitis C, in spite of normal absolute amounts of total NK-cells. It was revealed that the levels of NK-cells and their activated forms did not did not depend on HCV genotype (1 vs 3). Likewise, they did not differ between the patients with higher and lower viral load. When analyzing relationships between the contents of activated NK cells and levels of biochemical markers of cytolytic and cholestatic syndromes, we have found a direct correlation with AST activity, and an inverse correlation with the of GGT and alkaline phosphatase activities. The data suggest a possible role of altered NK cell activation in pathogenesis of chronic hepatitis C.

Abstract. This work presents immunological data of one-hundred patients with severe pyoinflammatory diseases of face and neck area. Upon laboratory evaluation of patients with such pathology, it was shown that production of IL-1β, IL-2, IL-6, IL-8, IL-10, Rа-IL-1β is induced in this cohort. A clinically unfavorable pattern of cytokine profile was specified in patients with severe pyoinflammatory diseases of face and neck region. Its common feature is an imbalance in cytokine network associated with overproduction of immunosuppressive cytokines.

Abstract. Supervision over 70 patients with acute no lymphoblastic leukemia and 65 patients with acute lymphoblastic leukemia, admitted in hematological department of Regional clinical hospital of № 1 of Krasnoyarsk city were made. It was established, that at a combination of G6PDG activity in blood lymphocytes in limits from 10,02 to 32,74 mkU and NADPMDG in limits from 8,29 to 15,37 mkU the development of infectious complications in patients with acute leukemia after chemotherapy is predicted.