Peripheral blood T helper cell subsets in Löfgren’s and non-Löfgren’s syndrome patients

Sarcoidosis is a multisystemic granulomatous disorder of unknown cause, characterized by formation of immune granulomas in various organs, mainly in lungs. Currently, two main phenotypes of pulmonary sarcoidosis are described, i.e., Lofgren’s syndrome (LS) is an acute form with favorable outcome, and non-Lofgren’s syndrome (nLS) is a chronic type of disease with a high risk of pulmonary fibrosis. Our study was aimed to investigate the balance of main “polarized” CD4+ central and effector memory T cells from treatment-naive patients with pulmonary sarcoidosis (LS (n = 19) and nLS (n = 63)) compared to healthy volunteers (HC, n = 48). This marker might be used as immunological markers for predicting severity of this disorder. Multicolor flow cytometry analysis demonstrated that the patients with nLS showed significantly low levels of relative and absolute numbers of CD3+CD4+ lymphocytes if compared to patients with LS and control group (38.94% (31.33-44.24) versus 48.96% (43.34-53.54) and 47.63% (43.82-52.73), p < 0.001 in both cases). Moreover, patients with nLS had reduced frequencies and absolute numbers of “naive”, CM and EM Th cells if compared with healthy controls. Furthermore, the patients with LS showed increased relative and absolute numbers of peripheral blood EM Th cells, capable for migration to peripheral inflamed tissues, when compared with nLS. Finally, patients with LS had increased frequencies and absolute numbers of effector TEMRA Th cells as compared to HC and nLS. Next, significant differences Th1 and Th2 cells frequencies were shown between the patients with nLS and HC (9.64% (7.06-13.65) versus 13.80% (11.24-18.03) with p < 0.001, and 11.96% (9.86-14.78) versus 10.67% (9.13-12.98) with p = 0.048, respectively). But there were no significant differences in the relative numbers of CXCR5-CCR6+Th17 and CXCR5+ follicular T helper cells (Tfh) between the groups. Finally, both groups of patients with pulmonary sarcoidosis contained low proportions of “non-classical” Th17 and DN Th17 cell, but increased levels of DP Th17 cells within total CXCR5-CCR6+ CM Th if compared with HC. Nevertheless, patients with nLS had increased frequency of “classical” Th17 in comparison with healthy controls. A very similar imbalance between different Th17 cell subsets was observed within total CXCR5CCR6+ effector memory Th, that were able to migrate from the bloodstream to the sites of infection, or tissue injury. Taken together, the data suggest that the proportions of Th17 cell subsets in pulmonary sarcoidosis can be evaluated as a diagnostic and/or prognostic marker in clinical practice and these cells could serve as a new therapeutic target

Peripheral blood B cell subsets from patients with various activity of chronic sarcoidosis

Sarcoidosis is an inflammatory disease of unknown etiology, characterized by development of necrosis-free epithelioid cell granulomas, resulting in hyperactivation of various cells of the immune system. The role of humoral mechanisms in the pathogenesis of sarcoidosis is less studied than cell-mediated. It is necessary to study the role of activation or the anergy of the B cell development of immunity in sarcoidosis, the degree of its activity and the characteristics of the clinical course of the disease. Our study was aimed at investigating the characteristics of the B cells subsets in the peripheral blood of patients with chronic sarcoidosis (n = 41), depending on the activity of the disease. The control was peripheral blood samples from healthy volunteers (n = 43). Objective clinical and instrumental criteria, angiotensin converting enzyme (ACE) were used to determine the activity of the disease. Using flow cytometry analysis of peripheral blood cell B cells were determined based on two approaches: expression of IgD/CD38 (“Bm1-Bm5” classification) and IgD/CD27. In patients with sarcoidosis there was a significantly higher relative number of Bm2 "activated" naive cells" (IgD+CD38+) than in conditionally healthy volunteers, 65.38% versus 55,66% (p < 0.001). The relative and absolute contents of eBm5 (IgD-CD38+) and Bm5 (IgD-CD38+) memory cells were significantly lower in the group of patients with sarcoidosis relative to the control group. Relative values: 6.59% versus 13.31%, (p < 0.001), and 3.43% versus 8.49%, (p < 0.001), respectively. It was shown that with an increased level of ACE in the peripheral blood of patients, the number of naive Bm1 cells (IgD+CD38-) was significantly reduced, r = -0.557, p < 0.001. The relative content of memory B cells that did not switch the class of synthesized antibodies (IgD+CD27+) in the group of patients was reduced to 6,25%, and in the control group — 12,95% (p<0.001). The number of memory cells that switched the class of synthesized antibodies (IgD-CD27+) was also significantly reduced in patients with sarcoidosis and amounted to 6.75% versus 16.50% in the control group (p < 0.001). In patients with high levels of ACE, there was an increase in the relative content of naive B cells (IgD+CD27-), r = 0.532, p < 0.001. An inverse relationship was established between the number of memory B cells (IgD+CD27+) and ACE levels, r = -0.565, p < 0.001. These results indicate the important role of the B cell immune response in the pathogenesis of sarcoidosis and make it possible to evaluate the characteristics of the humoral response with various degrees of disease activity

Sarcoidosis clinical picture governs alterations in type 17 T helper cell subset composition and cytokine profile

Immune cell hyperactivation along with cytokines they overproduce plays an important role in sarcoidosis and related disease pathogenesis. A central place in the immunopathogenesis of sarcoidosis is held by diverse cell-mediated reactions governed by T helper (Th) cell populations including Th17 subsets and relevant signature cytokines. We studied peripheral blood plasma samples of the patients with sarcoidosis (n = 123): 18% with acute and 82% with chronic course. The control group — samples from healthy volunteers (n = 43). T cell subset composition was assessed by flow cytometry. Cytokine concentrations (pg/mL) were measured by multiplex analysis using xMAP technology (Luminex). The level of “classical” Th17 turned out to be significantly reduced in acute vs chronic sarcoidosis: 28.3% vs 33.3% (p = 0.046). The level of “double-positive” Th17 (DP Th17) was significantly increased in chronic and acute vs control group: 31.7% and 34.2% vs 26.2% (p < 0.001 in both cases), without differences patient inter-group; “non-classical” Th17.1 were shown to have significantly reduced level only in chronic vs healthy subjects: 27.9% and 35.9% (p < 0.001). Clinical and laboratory diagnostic characteristics for blood DP Th17 levels in CD45RA-negative Th effector memory cells in sarcoidosis: in acute sarcoidosis vs healthy subjects, they were characterized by sensitivity — 82%; specificity — 71%, whereas in chronic: 67% and 56%, respectively. In patients with sarcoidosis vs healthy subjects were found to have significantly increased level of IL-12 (p70) — 1.3 vs 0.56, p = 0.028; IL-17A — 1.5 vs 0.43, p < 0.001; IFNγ — 4.1 vs 1.1, p < 0.001; TNFα — 21.7 vs 6.7, p < 0.001. Thus, CCR6+ Th17 and DP Th17 subsets and relevant signature cytokines are important in diagnostics of sarcoidosis of varying clinical course: a direct correlation was shown between the level of angiotensin-converting enzyme activity and percentage of memory DP Th17; disease progression vs regression had significantly reduced absolute number of total CD45RA- memory and CM Th17; extrapulmonary manifestations had a significantly increased percentage of DP Th17 CD45RA- and EM DP Th17; in chronic sarcoidosis are significantly increased concentration of IL-17A, IFNγ, IL-12 and positively correlation between IFNγ and the activity of angiotensin-converting enzyme

Elastic properties of mono- and polycrystalline hexagonal AlB2-like diborides of s, p and d metals from first-principles calculations

We have performed accurate ab initio total energy calculations using the full-potential linearized augmented plane wave (FP-LAPW) method with the generalized gradient approximation (GGA) for the exchange-correlation potential to systematically investigate elastic properties of 18 stable, meta-stable and hypothetical hexagonal (AlB2-like) metal diborides MB2, where M = Na, Be, Mg, Ca, Al, Sc, Y, Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W, Ag and Au. For monocrystalline MB2 the optimized lattice parameters, independent elastic constants (Cij), bulk modules (B), shear modules (G) are obtained and analyzed in comparison with the available theoretical and experimental data. For the first time numerical estimates of a set of elastic parameters of the polycrystalline MB2 ceramics (in the framework of the Voigt-Reuss-Hill approximation), namely bulk and shear modules, compressibility, Young's modules, Poisson's ratio, Lame's coefficients are performed.Comment: 24 pages, 3 figure

Features of self-concept of adolescents who are brought up in the conditions of paternal deprivation

Introduction: this article deals with the problem of personal development of adolescents who are brought up in the conditions of paternal deprivation, on the example of the content aspects of the main components of their Self-concept. On the basis of the analysis of the actual data presented in modern studies, the trend of growth in the number of incomplete (maternal) families and the specifics of the development of children and adolescents from such families is stated. The author gives a general assessment of the degree of study of the problem of Self-concept in adolescence and shows its lack of development in relation to adolescents raised in conditions of paternal deprivation.Materials and Methods: a comparative analysis of the features of the content aspects of the main structural components of the Self-concept of adolescents from full and maternal families, a total of 170 people was carried out. The content characteristics of the cognitive component of the Self-concept –Self-image and the manifestations of the emotional component – Self-rating, including the general self-acceptance of adolescents are studied.Results: data of some specificity of the formation of Self-concept of adolescents who are brought up in the conditions of paternal deprivation were received. In particular, the study confirmed the hypothesis that paternal deprivation has a significant impact on the content of the adolescent’s Self-image, which is reflected in both quantitative and qualitative features of their Self-descriptions. In addition, the results of comparative analysis it was determined that the presence of adolescents who are brought up mothers to lower performance in most of the parameters of the Self-rating, except in the area of romantic relationships.Discussion and Conclusions: in general, the results of the study allowed identifying the predominant Self-representation of adolescents from full and maternal families, as well as the nature of their Self-rating in the most important parameters for this age

Psychological well-being of boys high school students with different variants of development of male identity

Introduction. This article is devoted to the problem of psychological well-being of the individual in the context of the formation of male identity, which has a socio-cultural character and is derived from the canons of masculinity adopted by the subject. The initial setting of the authors is the idea of multi-variant development of the male identity and consequently the availability of different types of this phenomenon. Some of the existing typologies of masculinity and masculine identity are considered. The arguments exposing the traditional standards of masculinity and the corresponding male identity are given. On the basis of the analysis of scientific primary sources the fragmentary nature of the study of certain aspects of psychological well-being of representatives of traditional variants of development of male identity is shown and the relevance of the study of this phenomenon in subjects with other variants of male identity is substantiated.Materials and Methods. In the logic of the typology of male identity N.K.Radina and A.A.Nikitina and from the standpoint of the concept of psychological well-being K.Riff in line with the emic-approach studied the specificity of the manifestation of the General level and the main components of psychological well-being in representatives of different options for the development of male identity in relation to early adolescence. A comparative analysis of the types of male identity in high school boys from full and incomplete (maternal) families is also carried out.Results. The data confirmed the validity of the assumption that the majority of young men from incomplete (maternal) families are characterized by Patriarchal and hybrid types of male identity, while their peers from full families, along with Patriarchal and hybrid order of magnitude more common alternative options for the development of male identity. It is stated that there are statistically significant differences in the majority of components of psychological well-being in young men with different types of male identity, most of which are recorded in favor of the subjects with alternative and less – Patriarchal options for the development of male identity. In addition, it was found that the highest rates of overall psychological well-being observed in young men – representatives of alternative types of male identity.Discussion and Conclusions. According to the results of the study, it is concluded that it is necessary to soften the traditional norms of masculinity and to give a legitimate status to alternative standards and models of male behavior

CD39⁺ EXPRESSION BY REGULATORY T CELLS IN PULMONARY SARCOIDOSIS AND LOFGREN’S SYNDROME

Sarcoidosis is a disorder of unknown etiology characterized by development of necrosis-free epithelioid cell granulomas in various tissues. There are two main phenotypes of pulmonary sarcoidosis (PS): Lofgren’s syndrome (LS) is an acute form with favorable outcome, while non-Lofgren’s syndrome (nLS) is a chronic type of disease that can lead to pulmonary fibrosis in 20% of cases.Our study was aimed at investigating changes in the main cell-surface differentiation antigens on peripheral blood regulatory T cells (Tregs) from the patients with first diagnosed PS without treatment (LS, n = 11) and nLS (n = 46) compared to healthy volunteers (HC, n = 26).These indexes might be used as immunological markers for predicting severity of this disorder. Flow cytometry analysis of peripheral blood cell samples demonstrated that the nLS patients had decreased relative numbers of CD3+ cells vs healthy controls, as well as diminished CD3+CD4+ cells vs HC and LS patients. Furthermore, the relative and absolute Treg numbers were also decreased in nLS group vs HC (2.83% (2.47; 3.36) vs 3.33% (2.79; 3.84), p = 0.021), and 37 (29; 52) cells vs 50 (42; 65), p = 0.004, respectively) per one microliter of peripheral blood. Relative number of CD39-positive Тregs in chronic vs acute sarcoidosis patients was associated with 51.02% (38.20; 61.62) vs 48.64% (41.46; 63.72) that was significantly (p < 0.001 and p = 0.007, respectively) higher than in HC (39.52% (11.55; 46.34). We have found that “naïve” (CD45R0-CD62L+) Тregs did not significantly differ in percentage of CD39- and CD73-positive cells in all the groups tested. Moreover, CD45R0+CD62L+ Тregs in LS and nLS patients contained significantly more CD39-positive cells (69.66% (61.92; 79.34) and 67.62% (61.92; 79.34), respectively, compared to 47.55% (15.74; 65.32) in HC (p < 0.001 and p = 0.004, respectively). In case of CD45R0 + CD62LTregs able to exit from the circulation and migrate to the site of inflammation, an increased percentage of CD39-positive subset was noted only in patients with chronic sarcoidosis and HC (61.79% (55.12; 73.09) and 57.27% (16.03; 66.98), p = 0.006). Enhanced CD39 expression on Tregs seems to be related to chronic immune response, so that antigen elimination becomes impossible due to Treg overactivation, as shown in patients with sarcoidosis and some other chronic autoimmune and infectious disorders