Sarcoidosis is a multisystem inflammatory disease of unknown etiology characterized by the formation of non-caseating granulomas, most commonly in the lung tissue. It presents with two main forms: acute and chronic. Patients with chronic sarcoidosis tend to have a less favorable prognosis with a risk of developing lung fibrosis. Sarcoidosis development involves the activation of T cells, which release various chemokines and cytokines that stimulate the inflammatory process. The aim of our study was to investigate the role of the ratio between Th17 and Treg cells in the chronic course of sarcoidosis. We studied peripheral blood plasma samples from patients with chronic sarcoidosis (CS) (n = 101) and healthy individuals (HC) (n = 40). The diagnosis in CS patients was confirmed by histological methods. We determined the levels of Th17 and Treg (% of total lymphocytes) by flow cytometry. The concentration of cytokines (pg/ml) IL-17A and IL-10 was measured by multiplex analysis using Luminex xMap. Correlations between the Th17/Treg ratio and clinical parameters, including serum angiotensin-converting enzyme (sACE) activity level in the peripheral blood, forced expiratory volume in the first second (FEV1, %), fibrosis manifestations, and extrapulmonary manifestations were analyzed in CS patients. Our analysis revealed elevated levels of Th17 cells (p = 0.028) and decreased Treg levels (p = 0.026) in CS patients compared to healthy controls. This resulted in a significantly increased Th17/Treg ratio (p = 0.003) and IL-17A/IL-10 ratio (p < 0.001) in sarcoidosis patients. Furthermore, the Th17/Treg ratio positively correlated with sACE levels (p = 0.018), fibrosis manifestations (p = 0.019), and extrapulmonary manifestations (p = 0.016), and negatively correlated with FEV1% (p = 0.021). Our results indicate an increase in the Th17/Treg ratio, as well as the ratio of their main cytokines in patients with chronic sarcoidosis, which may emphasize their potential role as a diagnostic and prognostic biomarker of disease severity. At the molecular level, the balance between Treg and Th17 cells is maintained by the transcription factors Foxp3 and RORγt, which regulate the differentiation and function of these cells. Disruption of this balance in patients with chronic sarcoidosis may indicate a possible mechanism for disease progression.

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.

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.

Sarcoidosis is a multi-organ granulomatosis of unknown origin. Modern diagnostic methods allow detecting this disease at an early stage. The absence of specific markers requires a comprehensive approach to diagnosis based on comparison of radiation, clinical, morphological and functional data. The course of sarcoidosis without damage to the respiratory system presents significant difficulties. It is extremely important to understand the time and means of starting Sarcoidosis’s treatment to avoid the early initiation of hormones and cytostatics and, on the other hand, to timely respond to progression and threatening conditions. Methods. Clinical recommendations are based on the analysis of Russian and English publications of the latest sarcoidosis research. The target audience of these clinical guidelines are therapists, general practitioners, pulmonologists, TB doctors, rheumatologists, dermatologists, radiation diagnosticians, immunologists, and clinical pharmacologists. Each thesis-recommendation for diagnosis and treatment is evaluated on an 1 to 5 scale of levels of evidence and an A, B, C scale of the grades of recommendations. The clinical guidelines also contain comments and explanations for the theses-recommendations, diagnostic algorithms, treatment strategies, reference materials on the use of recommended drugs. Conclusion. Current information on epidemiology, clinical manifestations, diagnosis and management strategies for patients with sarcoidosis are covered in the presented clinical guidelines. Approved by the decision of the Scientific and Practical Council of the Ministry of Health of the Russian Federation (2022).

Various immune cells as well as related cytokines are involved in immunopathogenesis of sarcoidosis and mechanisms of granuloma development. Currently, a role for chemokines in sarcoidosis has been extensively investigated, which is paralleled with a search for key molecules necessary for recruiting immune cells to intrusion site and granuloma formation as well as affecting outcome of the latter. Our study was aimed for determining level of plasma CCL17/TARC and CCL22/MDC chemokines in patients with sarcoidosis who received no immunosuppressive therapy is of high priority for clarifying some aspects in underlying immunopathogenesis as well as seeking out for secure clinical and laboratory criteria for assessing activity and disease prognosis. We studied peripheral blood plasma samples of the patients with sarcoidosis (n = 52). In 37% (19/52), they exhibited acute clinical manifestations, and 63% (33/52) had chronic sarcoidosis. The control group included peripheral blood samples from healthy volunteers (n = 22). The chemokine concentrations (pg/ml) were determined by multiplex analysis using xMAP technology (Luminex), and Milliplex MAP test system (Millipore, USA). In the patients with sarcoidosis, significantly higher levels of chemokines were shown relative to healthy volunteers: CCL17 – 78.24 pg/ml vs 26.24 pg/ml, p < 0.001; CCL22 – 660.60 pg/ml vs 405.00 pg/ml, p < 0.001. Evaluation of clinical and laboratory diagnostic characteristics for plasma chemokine levels in sarcoidosis patients allowed to assess their sensitivity and specificity. The respective values were as follows: in acute sarcoidosis: for CCL17 – 63% and 78%, CCL22 – 63% and 91%; in chronic sarcoidosis: CCL17 – 58% and 83%, CCL22 – 67% and 86%, respectively. In chronic sarcoidosis the levels of this chemokine correlated with the activity of angiotensin-converting enzyme (ACE), for CCL17 (r = 0.530; p = 0.003), for CCL22 (r = 0.446; p = 0.014). Patients with systemic lesions vs no systemic lesions (sarcoidosis of the respiratory system only) had significantly elevated CCL17 level: 102.82 pg/ml vs 32.72 pg/ml, p = 0.011. The concentration of chemokine CCL17 was significantly increased in patients with vs without signs of hepatomegaly: 130.73 pg/ml vs 51.60 pg/ml, p = 0.022. Levels of chemokines was significantly increased in patients with vs without ultrasound signs of splenomegaly comprising: for CCL17 – 249.18 pg/ml vs 46.87 pg/ml, p = 0.002; for CCL22 – 1271.40 pg/ml vs 660.63 pg/ml, p = 0.003. Thus, it should be noted that the peripheral blood plasma level of chemokines CCL17 and CCL22 may be used as additional prognostic markers in chronic sarcoidosis with varying scoring of clinical signs including with/without systemic disease manifestations.

Sarcoidosis is a polysystemic inflammatory disease of unknown etiology, morphologically related to the group of granulomatosis, with heterogeneous clinical manifestations and outcomes. Immune cells, in particular T helper cells, are attracted to lung tissue and/or other organs by chemokine gradients and play an important role in the granuloma formation. T helper cells migrate from peripheral blood to the tissues due to expression of CXCR3 chemokine receptor on their surface. It interacts, e.g., with CXCL9/MIG, CXCL10/IP- 10, and CXCL11/I-TAC. Our study was aimed for determining the levels of CXCL9/MIG, CXCL10/IP-10, CXCL11/I-TAC chemokines in peripheral blood of the patients with sarcoidosis, depending on the features of their clinical course before administration of immunosuppressive therapy. We studied peripheral blood plasma samples of the patients with sarcoidosis (n = 52). In 37% (19/52), they exhibited acute clinical manifestations, and 63% (33/52) had chronic sarcoidosis. The control group included peripheral blood samples from healthy volunteers (n = 22). The chemokine concentrations (pg/ml) were determined by multiplex analysis using xMAP technology (Luminex), and Milliplex MAP test system (Millipore, USA). In the patients with sarcoidosis, significantly higher levels of chemokines were shown relative to healthy volunteers: CXCL9, 4013.00 pg/ml vs 1142.00 pg/ml (p < 0.001); CXCL10, 565.90 pg/ml vs 196.60 pg/ml (p < 0.001); CXCL11, 230.20 pg/ml vs 121.10 pg/ml (p = 0.018). Plasma concentrations of CXCL9 and CXCL10 were significantly increased both in blood samples from patients with acute and chronic sarcoidosis compared to healthy volunteers, p < 0.001. The level of CXCL11 chemokine was significantly increased only in the patients with chronic sarcoidosis, compared to the healthy volunteers: respectively, 251.50 pg/ml and 121.10 pg/ml (p = 0.044). The levels of this chemokine correlated with the activity of angiotensin-converting enzyme (ACE), with r = 0.374; p = 0.042. The ACE level in sarcoidosis is considered a clinical and laboratory index of the disease activity. In acute sarcoidosis, the level of CXCL11 chemokine was not significantly higher than in healthy individuals, whereas the CXCL9 chemokine content was significantly increased and correlated with ACE activity (r = 0.762; p = 0.037). The level of CXCL9 chemokine was significantly decreased in patients with signs of fibrosis as compared with fibrosis-free patients (1839.88 pg/ml vs 4375.52 pg/ml, p = 0.035). Significantly higher levels of CXCL9 were detected in cases of systemic sarcoidosis, i.e. 6036.84 pg/ml, as compared with 1927.44 pg/ml in the patients without these signs (p = 0.018). Evaluation of clinical and laboratory diagnostic characteristics for plasma chemokine levels in sarcoidosis patients allowed to assess their sensitivity and specificity. The respective values were as follows: in acute sarcoidosis: for CXCL9, 84% and 95%; for CXCL10, 84% and 95%; for CXCL11, 74% and 59%. In chronic sarcoidosis, the respective values for CXCL9 were 82% and 72%; for CXCL10, 91% and 77%; for CXCL11, 79% and 55%, respectively. Thus, the determination of plasma CXCL9, CXCL10, and CXCL11 chemokines in sarcoidosis allows of understanding their role in development of the disease, e.g., recruitment of T helper cells from peripheral blood to the lung tissue, and granuloma formation. Clinical and immunological comparisons of CXCL9 levels in the peripheral blood of patients and characteristics of the clinical course of sarcoidosis indicate to the role of this diagnostic parameter for assessing the disease activity, signs of lung fibrosis, and systemic manifestations in this disease.

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 is an inflammatory disease of unknown etiology with damage to the lungs and other organs characterized by development of necrosis-free epithelioid cell granulomas. Granulomatous inflammation characterized by the activation of different immune systems cells, in particular T lymphocytes, and the cytokines production. Our study was aimed at investigating the characteristics of the cytokine profile of blood plasma in patients with sarcoidosis. We studied peripheral blood plasma samples of patients with sarcoidosis (n = 52). The control blood samples were taken from healthy volunteers (n = 22). The level of 46 cytokines (pg/ml) was determined, as follows: IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL- 6, IL-7, IL-9, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A, IFNα2, IFNγ, TNFα, TNFβ, IL- 1ra, IL-10, EGF, FGF-2, Flt3 Ligand, G-CSF, GM-CSF, PDGF-AA, PDGF-AB / BB, TGFα, VEGF-A, sCD40L, CCL2, CCL3, CCL4, CCL5, CCL7, CCL11, CCL17, CCL20, CCL22, CXCL1, CXCL8, CXCL9, CXCL10, CXCL11, CXCL13, CX3CL1. Significantly higher levels of interleukins and some proinflammatory cytokines were found in the patients with sarcoidosis, i.e., IL-3, 0.70 vs 0.20, p = 0.003; IL-4, 14.37 vs 3.15, p = 0.009; IL-5, 1.06 vs 0.89, p < 0.001; IL-12 (p70), 1.27 vs 0.56, p = 0.028; IL-17A, 1.48 vs 0.43, p < 0.001; IFNα2, 41.79 vs 25.04, p = 0.003; IFNγ, 4.13 vs 1.14, p < 0.001; TNFα, 21.67 vs 6.70, p < 0.001; anti-inflammatory cytokine IL-10, 1.03 vs 0.45, p = 0.019; growth factors: FGF-2, 40.08 vs 30.58, p = 0.008, G-CSF, 24.18 vs 8.21, p = 0.006, and VEGF-A, 42.52 vs 26.76, p = 0.048; chemokines: CCL3, 3.86 vs 1.33, p < 0,001; CCL17, 78.24 vs 26.24, p < 0.001; CCL20, 7.19 vs 5.64, p = 0.021; CCL22, 660.60 vs 405.00, p < 0,001; CXCL9, 4013 vs 1142, p < 0,001; CXCL10, 565.90 vs 196.60, p < 0.001; CXCL11, 230.20 vs 121.10, p = 0.018; CX3CL1, 56.99 vs 5.16, p < 0.001. Peripheral blood chemokine CCL11 levels were significantly lower in patients compared to the group of healthy volunteers: 77.58 vs 124.70, p = 0.022. The features of the cytokine profile in patients with sarcoidosis may indicate their important role in the processes of formation and outcomes of granulomas. These issues require an additional detailed study, comparison with phenotypes, differential course and outcomes of the disease.

Myelopathy occurs in 1% of patients with sarcoidosis and is usually caused by the underlying disease. Comorbidity as its possible cause should be excluded, especially in a case of atypical neurosarcoidosis.Objective: to analyze the features of myelopathy in patients with systemic sarcoidosisPatients and methods. Twelve patients (7 women and 5 men) aged 41.5 [32.5; 45.3] years with systemic sarcoidosis and myelopathy were examined. The clinical and radiographic features of spinal cord (SC) injury and the nature of changes in laboratory parameters were analyzed.Results and discussion. The cause of myelopathy was sarcoidosis (neurosarcoidosis (NS)) in 7 (58%) patients (Group 1) and multiple sclerosis in 4 (33%) (Group 2). One more patient developed myopathy due to extradural lipomatosis (this case is described in the clinical observation section). In Group 1, myelopathy was the first manifestation of sarcoidosis in 4 (57%) of the 7 patients. Six (86%) patients were observed to have incomplete regression of symptoms; 5 (71%) showed a progressive course. Magnetic resonance imaging (MRI) revealed the signs of a lesion in the thoracic SC in 4 (57%) patients with NS, as well as damage to three or more of its segments in 5 (71%) and a radiological pattern of sarcoidosis-induced SC lesion in 6 (86%). MRI findings showed that all the 4 (100%) patients in Group 2 had cervical SC injury, no patterns typical of NS, as well as the signs of meningeal contrast agent accumulation. None of them displayed pleocytosis and low glucose levels in the cerebrospinal fluid. Extradural lipomatosis-induced myelopathy was compressive with positive changes after discontinuation of glucocorticoids.Conclusion. It is necessary to take into account the possibility of comorbidity as a cause of myelopathy in patients with sarcoidosis and the likelihood of SC lesion as a complication of therapy for the underlying disease.

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.

Страница 56 ЛУЧЕВАЯ ДИАГНОСТИКА ФИБРОЗИРУЮЩЕГО САРКОИДОЗА ОРГАНОВ ДЫХАНИЯ Амосов И.В., Сперанская А.А

Objective: to evaluate the clinical and radiological features of rare forms of sarcoidosis of the respiratory organs (SRO).Material and methods. In 2006 to 2016, the Research Institute of Interstitial and Orphan Lung Diseases followed up 599 patients with sarcoidosis. 36 patients (6.0%) of them had atypical clinical and radiation manifestations that did not correspond to the traditional radiation pattern and the existing X-ray classification of SRO. Stages 2, 3, and 4 pulmonary sarcoidosis was diagnosed in 26, 7, and 3 patients, respectively. The patients’ mean age was 38.2±7.4 years (the female/male ratio was 26:10). All the patients underwent traditional X-ray studies (radiography in two projections), high-resolution computed tomography (CT), complex external respiratory function examination, and echocardiography.Results. Analysis of the results of radiation examinations revealed the following rare forms of SRO: interstitial edematous, fibrous, and cavitary ones that had recognizable CT patterns. Each of these forms had clinical and functional features. In single cases, the CT pattern combined the features incompatible with the generally accepted classification (Stages 1 and 4 SRO); this was an offstage form. The features of the radiation pattern and clinical course required the differential diagnosis of these patients with more severe diseases (idiopathic pulmonary fibrosis, lymphogenic carcinomatosis, pulmonary edema, diffuse connective tissue diseases, pneumoconiosis, mycobacteriosis, and exogenous allergic alveolitis) and morphological verification.Conclusion. The accumulation of experience with clinical and radiological examination of patients with SRO revealed its rare forms that are difficult to diagnose and necessitate the development of new approaches to therapy policy.

Страница 85 КЛИНИКО-ЛУЧЕВАЯ ДИАГНОСТИКА ПРОЯВЛЕНИЙ ЛИМФАНГИОЛЕЙОМИОМАТОЗА ЛЕГКИХ (ЛАМ) Васильева М.А. 1 , Амосов В.И. 1 , Новикова Л.Н. 1 , Сперанская А.А. 1 , Баранова О.П. 1 , Амосов И.В. 1 , Фролова О

ДИНАМИКА КЛИНИКО-ЛУЧЕВЫХ ПРОЯВЛЕНИЙ ЛИМФАНГИОЛЕЙОМИОМАТОЗА ЛЕГКИХ (ЛАМ) ПРИ ДЛИТЕЛЬНОМ НАБЛЮДЕНИИАмосов В.И

The aim of the study was to estimate the contribution of angiotensinogen (AGT), transforming growth factor beta-1 (TGFB1), estrogen receptor alpha (ESR1), and vitamin D receptor (VDR) gene variants to IIP and PS development and course in residents of Russian Federation. Methods. This case-control study involved 104 IIP patients, 111 PS patients, and 113 controls. Seven single nucleotide polymorphisms were investigated using polymerase chain reaction followed by restriction analysis, namely rs5051 in AGT gene; rs1800469, rs1800470, and rs1800471 in TGFB1 gene; rs2234693 and rs9340799 in ESR1 gene; rs731236 in VDR gene. Results. We revealed associations of TGFB1 (rs1800469) and ESR1 (rs9340799) gene variants with IIP clinical outcomes, as well as AGT (rs5051) and VDR (rs731236) gene variants with PS stage. Unfavorable IIP outcomes, i.e. IIP progression or death, were associated with variants rs1800469 СС in TGFB1 gene (р = 0.021; odds ratio (OR) = 2.83; 95%CI: 1.16–6.94) and rs9340799 X (G) in ESR1 gene (р = 0.012; OR = 3.18; 95%CI: 1.27–8.00), as well as with their combination (р = 0.003; OR = 3.88; 95%CI: 1.55–9.71). PS stages II–IV were associated with variants rs5051 А in AGT gene (р = 0.010; OR = 3.22; 95%CI: 1.30–7.98) and rs731236 t (C) in VDR gene (р = 0.046; OR = 2.45; 95%CI: 1.00–6.02), as well as with their combination (р = 0.041; OR = 3.31; 95%CI: 1.14–9.60). Conclusion. Results of the study contribute to understanding genetic factors that influence IIP and PS courses.

Objective: to evaluate the clinical and radiological features of viral pneumonia caused by influenza A (H1N1) in 2015–2016. Material and methods. The study involved 22 patients (13 men, 9 women, 1 patient died) with viral pneumonia caused by influenza A (H1N1). The average age of patients was 39±14 years. All patients underwent conventional X-ray examinations (radiography in two projections), multi-spiral computed tomography (CT), high-resolution CT. Seven patients underwent CT angiography. Assessment of respiratory function was performed in 20 patients (except two severe patients that were unable to undergo the test). Results. The clinical course included rapid progression, with body temperature increase up to 39 °C or above, development of intoxication and respiratory failure. X-ray patterns were identical to the previous epidemic in 10 patients. Others showed rapid process progression leading to the formation of mixed infections (3 pts), development of respiratory distress syndrome (5 pts), complicated by pneumomediastinum and pneumothorax, pulmonary embolism accession (3 pts). Long-term retention of respiratory failure was caused by the formation of two types of lung pathology: severe constrictive bronchiolitis (in 5 patients receiving mechanical ventilation) and fibrotic changes in lung tissue resembling fibrosing alveolitis (6 patients without mechanical ventilation). Conclusion. The use of long-term mechanical ventilation in patients with severe viral lung lesions may complicate with constrictive bronchiolitis development. The formation of fibrotic changes in the lung tissue similar to idiopathic interstitial pneumonias may be the confirmation of their suspected viral nature. Development of pneumothorax and pneumomediastinum may be due to lung tissue changes caused by viral infection. Development of pulmonary embolism in viral lungs lesions requires inclusion of CT angiography in the diagnostic algorithm of complicated influenza.