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Dynamics of the level of transforming growth factors in blood serum in acute kidney injury in patients after coronary artery bypass grafting 冠状动脉旁路移植术后急性肾损伤患者血清转化生长因子水平的动态变化
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13544-dot
E. V. Markelova, V. G. Fisenko, Aleksandra A. Zenina, A. A. Silaev, M. Z. Yermolitskaya, V. B. Shumatov
Acute kidney injury (AKI) is among most dangerous and common complications after oper-heart cardiosurgical operations. Therefore, a search is carried out for biological markers which could timely detect this condition. The article presents dynamics of TGF-1, TGF-2, TGF-3 in blood serum prior and after a coronary artery bypass (CAB). The study included 120 patients with multivascular affection of coronary blood flow , and 50 conventionally healthy persons of similar age. The 1st group included 50 patients without evidence of AKI, the 2nd group consisted of 70 patients with AKI. Serum TGF-1, TGF-2, TGF-3 was determined by ELISA technique in the main groups before (1) and after surgery (2) as well as on day 2 after operation (3), on day 7 after surgery (4), and once tested in the control group.. The results were expressed in ng/mL or pg/mL, as median values, upper and lower quartiles. Significance levels were determined by the Wilcoxon criterion. We have revealed dynamic changes of TGF- levels in serum of the patients before and after CAB. Initially, before operation, we have found normal TGF-1 levels and low TGF-3 levels in the both main groups. Meanwhile, increased TGF-2 levels are found only in the subgroup with subsequent AKI development. The dynamics of TGF-1 showed a decrease just after surgery and 2 days later, being increased over initial level on day 7, and there were no significant differences for the groups with versus without complications. No dynamic differences were revealed for TGF-2 in the patients of group 1 after surgery. Meanwhile, the group 2 after CAB displayed higher TGF-2 values compared with controls during the entire follow-up period, neing, however, higher that in the group on the 2nd day following surgery. The TGF-3 levels were increased just after surgery in both groups followed by subsequent decrease in group 1. In the 2nd group after CAB, the initial deficiency of TGF-3 was changes in wave-like mode, over 2nd and 3rd period of monitoring. It was increased on day 7, becoming higher than in group1 but did not reach reference values. Further studies in the AKI group after CAB which depend on their severity and outcomes may detect new features of TGF- system in the patients with this disorder.
急性肾损伤(AKI)是心内直视手术后最危险和最常见的并发症之一。因此,寻找能够及时发现这种情况的生物标志物。本文介绍了冠状动脉搭桥术(CAB)前后血清TGF-1、TGF-2、TGF-3的动态变化。该研究包括120例冠状动脉血流受多血管影响的患者和50名年龄相仿的常规健康人。第一组50例无AKI证据,第二组70例有AKI。采用ELISA技术检测各组患者术前(1)、术后(2)、术后第2天(3)、术后第7天(4)血清TGF-1、TGF-2、TGF-3水平,对照组检测1次。结果以ng/mL或pg/mL表示,作为中位数,上、下四分位数。显著性水平由Wilcoxon标准确定。我们观察了CAB前后患者血清TGF-水平的动态变化。最初,在手术前,我们发现两组患者TGF-1水平正常,TGF-3水平低。同时,TGF-2水平升高仅在随后发生AKI的亚组中发现。术后和术后2天TGF-1动态下降,术后第7天较初始水平升高,有并发症组和无并发症组之间无显著差异。1组患者术后TGF-2无动态差异。同时,CAB后2组在整个随访期内TGF-2值均高于对照组,但术后第2天的TGF-2值高于对照组。两组术后TGF-3水平均升高,组1术后TGF-3水平下降。在CAB后的第二组中,TGF-3的初始缺乏在监测的第2和第3期呈波浪形变化。在第7天有所增加,高于第1组,但未达到参考值。对CAB后AKI组的进一步研究,取决于其严重程度和预后,可能会发现该疾病患者TGF-系统的新特征。
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引用次数: 0
<i>In vitro</> effects of recombinant IFNα2B on the content of antigen-presenting CD66b<sup>+</sup>CD16<sup>+</sup>CD33<sup>+</sup>HLA<sup>-</sup>DR<sup>+</sup> subset of neutrophils in children with acute osteomyelitis & lt; i&gt vitro&lt; /比;重组IFNα2B对呈递抗原cd66 &lt;sup&gt;+&lt;/sup&gt;CD16&lt;sup&gt;+&lt;/sup&gt;CD33&lt;sup&gt;+&lt;/sup&gt;HLA&lt;sup&gt;-&lt;/sup&gt;DR&lt;sup&gt;+&lt;/sup&gt;急性骨髓炎患儿中性粒细胞亚群
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13769-ive
I. V. Nesterova, Galina A. Chudilova, Yu. V. Teterin, E. A. Chicherev, V. N. Chapurina, V. A. Tarakanov, N. K. Barova
Negative impact of S. aureus, seems to be a sufficient condition for the spread of the infectious process in the bone in acute osteomyelitis (AOM) due to its altered elimination caused by dysfunction of the immune system (IS), in particular, of neutrophilic granulocytes (NG). Correction of NG dysfunction in AOM under the influence of immunotropic substances and cytokines via modulation of the NG phenotypic subsets is of sufficient interest. Our aim was to evaluate the in vitro effects of recombinant IFN2b on the number and phenotype of CD66b+CD16+CD33+HLA-DR-, CD66b+CD16+CD33+HLA-DR+ subsets and on phagocytic function of neutrophilic granulocytes in acute osteomyelitis in children. The study of peripheral blood (PB) samples from children aged 8-15 years was carried out as follows: patients with АOM (n = 24) comprised study group 1 (SG1), healthy children (n = 13) were included into comparison group (CG). PB samples of children with AOM were incubated with recIFN2b (50 IU/L, 60 min, 37 C.) in the study group 1a (SG1a). Before and after incubation with recIFN2b, the number of NG subsets CD66b+CD16+CD33+HLA-DR-, CD66b+CD16+CD33+HLA-DR+ and the density values of receptor expression by fluorescence intensity (MFI) were also determined (FC 500, Beckman Coulter, США). Phagocytic activity of NCs was evaluated as the contents of actively phagocytic NCs (%PhAN), volume of the engulfed S. aureus (strain 209) by assessing their phagocytic number (PhN), phagocytic index (PhI). Bacterial killing was determined as the percentages of microbe digestion (%D), digestion index (DI). The cells from AOM patients revealed a subset expressing the HLA-DR receptor СD66b+CD16+CD33+HLA-DR+NG, which is absent in the PB of CG children. The cells with primed phenotype exhibited an increased expression density of activation receptors CD16 and CD66b. Incubation of PB in AOM with recIFN2b led to an increased proportion of CD66b+CD16+CD33+HLA-DR+ NG subset which showed active phagocytosis and improved digestion processes. The present study shows the emergence of activated subset of long-lived CD66b+CD16+CD33+HLA-DR+ NCs in children with AOM. This subpopulation has APC features, by presenting AG to T lymphocytes, with preserved effector properties. In an in vitro experimental system, a positive effect of recIFN2b was demonstrated, leading to an increased number of NGs of the CD66b+CD16+CD33+HLA-DR+ subset and recovery of S. aureus phagocytosis by NGs, thus being promising in the future for development of new approaches to optimization of complex therapy in the postoperative period of AOM treatment, prevention of complications and the opportunity to alleviate the disorders in the immune system.
金黄色葡萄球菌的负面影响似乎是急性骨髓炎(AOM)中感染过程传播的充分条件,这是由于免疫系统(IS),特别是中性粒细胞(NG)的功能障碍导致其消除改变。在免疫亲性物质和细胞因子的影响下,通过调节NG表型亚群来纠正AOM中NG功能障碍是值得关注的。我们的目的是评估重组IFN2b在体外对急性骨髓炎儿童中CD66b+CD16+CD33+HLA-DR-、CD66b+CD16+CD33+HLA-DR+亚群数量和表型的影响,以及对中性粒细胞吞噬功能的影响。8-15岁儿童外周血(PB)样本的研究如下:研究1组(SG1)为АOM患者(n = 24),对照组(CG)为健康儿童(n = 13)。实验组1a (SG1a)中,AOM患儿PB样本与recIFN2b (50 IU/L, 60 min, 37℃)孵育。用recIFN2b孵化前后,测定NG亚群CD66b+CD16+CD33+HLA-DR-、CD66b+CD16+CD33+HLA-DR+的数量,荧光强度(MFI)测定受体表达密度值(FC 500, Beckman Coulter, США)。通过对吞噬数(PhN)、吞噬指数(PhI)的测定,以活性吞噬细胞的含量(%PhAN)、吞噬金黄色葡萄球菌(菌株209)的体积来评价吞噬细胞的吞噬活性。细菌杀灭测定为微生物消化百分比(%D)、消化指数(DI)。 AOM患者的细胞中有一个表达HLA-DR受体СD66b+CD16+CD33+HLA-DR+NG的亚群,而CG患儿的PB中不存在该亚群。激活受体CD16和CD66b的表达密度增加。用recIFN2b在AOM中培养PB,导致CD66b+CD16+CD33+HLA-DR+ NG亚群比例增加,表现出活跃的吞噬和改善的消化过程。目前的研究表明,AOM儿童中出现了活化的长寿命CD66b+CD16+CD33+HLA-DR+ nc亚群。该亚群具有APC特征,通过向T淋巴细胞呈递AG,保留了效应特性。在体外实验系统中,证实了recIFN2b的积极作用,导致CD66b+CD16+CD33+HLA-DR+亚群的ng数量增加,并恢复了金黄色葡萄球菌的吞噬作用,从而为AOM治疗术后优化复合治疗的新方法的开发,预防并发症和缓解免疫系统紊乱提供了机会。
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引用次数: 0
A clinical case of secondary eosinophilia in a child 儿童继发性嗜酸性粒细胞增多症1例
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13828-acc
V. G. Mukhametzyanova, Olga G. Rybakova, P. M. Palchenko, S. Y. Петрунина
A couple of decades ago, the diagnostic search for the cause of blood eosinophilia concerned, mainly, the three major allergic diseases (bronchial asthma, allergic rhinitis, atopic dermatitis), or parasitic invasion. In recent years, more and more complex clinical syndromes, from reactive (secondary) eosinophilia to eosinophilic leukemia are increasingly considered by the doctors of different specialties. The aim of our work was to present a clinical case of secondary eosinophilia in a child with minimal clinical manifestations. Highlights: Sometimes blood eosinophilia in a patient is an unexpected finding for a physician, especially if the complaints are scanty, nonspecific, and objective examination does not reveal any significant health abnormalities. In the presented case, secondary (reactive) peripheral blood eosinophilia was diagnosed due to intestinal damage induced by food allergens. This clinical case is of practical interest to physicians, presenting a diagnostic search for the cause of blood eosinophilia, which eventually proved to be a mixed IgE/ non-IgE mediated food allergy manifesting as allergic enterocolitis. The IgE-mediated mechanism of food allergy is evidenced by a high level of IgE and its decrease with administered elimination diet; delayed-type response and low severity of clinical manifestations of food allergy, as well as blood eosinophilia suggest a non-IgE mediated food allergy. In this particular case, the severity of laboratory changes (blood eosinophilia, a significant increase in the levels of specific IgE) was associated with scarce intestinal symptoms. An opposite situation is observed, especially, in young children where the disease manifests with a pronounced clinical pattern of enterocolitis in the absence of laboratory changes.
几十年前,对血嗜酸性粒细胞增多病因的诊断研究关注的,主要是三大过敏性疾病(支气管哮喘、变应性鼻炎、特应性皮炎)或寄生虫侵袭。近年来,越来越多复杂的临床综合征,从反应性(继发性)嗜酸性粒细胞增多到嗜酸性粒细胞白血病,越来越多地被不同专业的医生所重视。我们的工作的目的是提出继发性嗜酸性粒细胞增多症的临床病例在一个孩子最小的临床表现。要点:有时患者嗜酸性血友病对医生来说是一个意外的发现,特别是如果主诉很少,非特异性,客观检查没有发现任何重大的健康异常。在本病例中,继发性(反应性)外周血嗜酸性粒细胞增多被诊断为由食物过敏原引起的肠道损伤。本临床病例对医生具有实际意义,对血液嗜酸性粒细胞增多症的病因进行了诊断,最终证明是IgE/非IgE介导的混合食物过敏,表现为过敏性小肠结肠炎。IgE介导的食物过敏机制可以通过高水平的IgE和给药消除饮食的降低来证明;食物过敏的临床表现为延迟型反应、低严重程度以及血嗜酸性粒细胞增多,提示非ige介导的食物过敏。在这一特殊病例中,实验室变化的严重程度(血嗜酸性粒细胞增多,特异性IgE水平显著升高)与罕见的肠道症状相关。观察到相反的情况,特别是在幼儿中,在没有实验室变化的情况下,疾病表现为小肠结肠炎的明显临床模式。
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引用次数: 0
Coordination of the NF-κB signaling pathway and lymphocyte metabolism in children with autoimmune diseases 自身免疫性疾病儿童NF-κB信号通路与淋巴细胞代谢的协调
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13800-cot
Olga V. Kurbatova, T. V. Radygina, D. G. Kuptsova, S. V. Petrichuk, G. B. Movsisyan, A. S. Potapov, N. N. Murashkin, L. M. Abdullaeva, A. P. Fisenko
Metabolic aberrations underlie many chronic diseases, including autoimmune diseases (AUD). Immune metabolism is an area of immunological research that is actively developing and studying the processes of metabolic reprogramming in immune cells. The regulation of the nuclear factor kappa B (NF-B) activity, which is involved in the coordination of innate and adaptive immunity, inflammatory reactions and other processes, is being actively studied. The studies on immune metabolism and regulation of NF-B is a promising direction in searching for new therapeutic approaches in the AUD treatment. The aim of the present study was to evaluate the informative value of NF-B and the activity of intracellular lymphocyte succinate dehydrogenase (SDH) and glycero-3-phosphate dehydrogenase (GPDH) determined in children with immune-dependent disorders. 350 children with autoimmune diseases were examined: 97 patients with IBD, 72 children with relapsing-remitting multiple sclerosis (MS), 83 pediatric patients with psoriasis vulgaris (PS), and 97 children with autoimmune hepatitis (AIH). The comparison group consisted of 100 conditionally healthy children. Activity of mitochondrial dehydrogenases, i.e., SDH and GPDH, was evaluated by immunocytochemical method. The levels of NF-B translocation (per cent of cells with NF-B translocation from cytoplasm to cell nucleus) was determined by flow cytometry, with visualization. Statistical evaluation and plotting were carried out using the Statistica 13.0 software. The highest activity of SDH and GPDH was detected in the population of cytotoxic T lymphocytes and T helper cells, and the lowest activity of the enzymes was registered in the population of B lymphocytes, both in children with AUD and in comparison group. In children with AUD, there was a significant decrease in SDH activity in T lymphocytes, cytotoxic T lymphocytes, B lymphocytes and NK cells against the comparison group (p 0.01). In children with PS, AIH and IBD, a decrease in SDH activity was revealed in Treg and Th17 cells. The most pronounced decrease in GPDH was characteristic of patients with AH (in T cells, cytotoxic T lymphocytes, B cells, NK cells and Tregs against the comparison group). In children with PS, the activity of GPDH was reduced only in Tregs (p 0.05). For children with multiple sclerosis, a decrease in GPDH was revealed in populations of T lymphocytes, B lymphocytes and activated T helpers (p 0.01). In the group of patients with IBD, there were no significant differences in the activity of GPDG relative to the comparison group. A significant increase in the level of NF-B translocation in T helpers was revealed in all children with AUD relative to the comparison group. In children with AIH and PS, a significant increase in the level of NF-B translocation was revealed in Treg, Thact and Th17 cells, in children with MS it was found in Treg cells, in patients with IBD, it was registered in Thact against the comparison group (p 0.05). An inverse
代谢异常是许多慢性疾病的基础,包括自身免疫性疾病(AUD)。免疫代谢是免疫学研究的一个领域,正在积极发展和研究免疫细胞的代谢重编程过程。核因子κ B (NF-B)活性的调节参与先天免疫和适应性免疫、炎症反应等过程的协调,目前正在积极研究中。研究NF-B的免疫代谢和调控是寻找AUD治疗新途径的一个有希望的方向。本研究的目的是评估NF-B和免疫依赖性疾病儿童细胞内淋巴细胞琥珀酸脱氢酶(SDH)和甘油-3-磷酸脱氢酶(GPDH)活性测定的信息价值。350名患有自身免疫性疾病的儿童接受了检查:97名IBD患者,72名复发-缓解型多发性硬化症(MS)儿童,83名寻常性牛皮癣(PS)儿童和97名自身免疫性肝炎(AIH)儿童。对照组由100名条件健康儿童组成。免疫细胞化学法测定线粒体脱氢酶SDH和GPDH的活性。流式细胞术显示NF-B易位水平(NF-B从细胞质易位到细胞核的细胞百分比)。采用Statistica 13.0软件进行统计评价和绘图。在AUD患儿和对照组中,SDH和GPDH在细胞毒性T淋巴细胞和T辅助细胞群体中活性最高,在B淋巴细胞群体中活性最低。与对照组相比,AUD患儿T淋巴细胞、细胞毒性T淋巴细胞、B淋巴细胞和NK细胞中SDH活性显著降低(p < 0.01)。在患有PS、AIH和IBD的儿童中,Treg和Th17细胞中SDH活性下降。与对照组相比,AH患者的GPDH下降最为明显(T细胞、细胞毒性T淋巴细胞、B细胞、NK细胞和Tregs)。在PS患儿中,GPDH活性仅在Tregs中降低(p 0.05)。在多发性硬化儿童中,GPDH在T淋巴细胞、B淋巴细胞和活化T辅助细胞群中下降(p < 0.01)。在IBD患者组中,GPDG的活性与对照组相比没有显著差异。与对照组相比,所有AUD患儿的辅助T细胞中NF-B易位水平显著升高。在AIH和PS患儿中,NF-B易位水平在Treg、Thact和Th17细胞中显著升高,在MS患儿中,在Treg细胞中发现NF-B易位水平,在IBD患儿中,在Thact中与对照组比较,差异有统计学意义(p < 0.05)。淋巴细胞群中NF-B易位水平与淋巴细胞中线粒体脱氢酶活性呈负相关。最显著的依赖性是NK细胞和T细胞群的特征,这些相关性对所有AUD患者组都有效。在体外代谢作用药物实验过程中,观察到NF-B易位细胞数量减少,SDH活性增加;SDH的激活程度取决于细胞群类型,其中T淋巴细胞(61%)、B淋巴细胞(30%)和NK细胞(19%)的变化最大。淋巴细胞代谢活性和NF-B信号通路的研究使我们能够评估各种病因的自身免疫性疾病儿童免疫病理过程的一般机制。基于淋巴细胞中NF-B易位水平与SDH活性之间的负相关关系,人们可以考虑使用一种可用的免疫细胞化学方法作为评估NF-B转录因子活性的类似物。研究免疫活性细胞的免疫代谢校正是AUD治疗的一个有前景的方向。
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引用次数: 0
Features of immune status in patients with acute coronary syndrome with and without COVID-19, depending on the level of B1 lymphocytes 伴有和不伴有COVID-19的急性冠状动脉综合征患者免疫状态特征与B1淋巴细胞水平的关系
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13989-foi
Eleanora A. Safronova, L. V. Ryabova, A. V. Zurochka
The aim of our study was to evaluate the blood cell indices and phagocytic activity of neutrophils in persons with acute coronary syndrome, depending on their history of COVID-19 infection. The study involved 65 males aged 35 to 65 years with acute coronary syndrome (acute myocardial infarction and unstable angina pectoris). All patients underwent coronary angiography and stenting of the coronary arteries within 3 days from the terms of admission to the hospital. The following clinical examination were carried out: a general blood test by a standardized method on a hematological analyzer Medonic M20 (Sweden). Of immunological indices, the phagocytic activity of neutrophils was assessed. Spontaneous and induced NBT test of neutrophils was determined by light microscopy using light microscopy (Olimpus, Japan). The phagocytic activity of neutrophils was recorded by their ability to absorb latex particles. B1 lymphocytes were determined using flow cytometry. All patients, depending on the content of B1 lymphocytes and the presence or absence of COVID-19 in previous history, were divided into 6 groups: patients with COVID-19 and those with reduced (group 1), normal (group 2), or elevated number of B1 lymphocytes (group 3). The patients who did not have COVID-19 were also classified into those with low (group 4), normal (group 5), or elevated B1 lymphocytes (group 6). The numbers of leukocytes in routine blood test were significantly higher, and the average corpuscular volume of hemoglobin was lower in the patients who have undergone COVID-19. Platelet counts were higher in post-COVID-19 patients, being maximal at normal B1 lymphocytes. The largest number of monocytes was recorded in patients with COVID-19 and normal B1 lymphocytes, and the minimal content of monocytes was registered in patients of group 4. The highest number of granulocytes was observed in individuals who did not have COVID-19, with reduced B1 lymphocytes. Thrombocytocrit was the highest in group 2 patients. The activity and intensity of neutrophil phagocytosis was lower in individuals with a history of COVID-19 and elevated B1 lymphocytes. The phagocytic number of neutrophils was minimal in those patients without COVID-19 who had low B1 lymphocytes. The maximal spontaneous HBT activity was recorded in individuals with high B1 lymphocytes and a history of COVID-19, and the minimal values have been recorded in those with low B1 lymphocytes and previous COVID-19. NBT spontaneous index was also the highest in patients of the 3rd group. The minimal NBT-induced activity and index were noted in group 1. The most severe patients were in groups 1 and 2. In group 1, 50% were diagnosed with acute myocardial infarction, stent thrombosis was diagnosed in 2 patients, four patients deceased. Among patients with normal B1 cell contents and a history of COVID-19, 2 patients died, 2 patients had stent thrombosis, 65% had acute myocardial infarction. These groups had higher platelet levels
我们的研究目的是评估急性冠状动脉综合征患者的血细胞指数和中性粒细胞的吞噬活性,这取决于他们的COVID-19感染史。该研究涉及65名患有急性冠状动脉综合征(急性心肌梗死和不稳定型心绞痛)的男性,年龄在35至65岁之间。所有患者均在入院后3天内行冠状动脉造影和冠状动脉支架置入术。进行了以下临床检查:在Medonic M20(瑞典)血液分析仪上采用标准化方法进行一般血液检查。在免疫学指标方面,评价了中性粒细胞的吞噬活性。用光学显微镜(Olimpus, Japan)测定中性粒细胞自发和诱导的NBT试验。中性粒细胞的吞噬活性是通过它们吸收乳胶颗粒的能力来记录的。流式细胞术检测B1淋巴细胞。 所有患者根据B1淋巴细胞含量及既往有无COVID-19病史分为6组:新冠肺炎患者和B1淋巴细胞降低(1组)、正常(2组)、升高(3组)。未感染新冠肺炎的患者又分为B1淋巴细胞低(4组)、正常(5组)、升高(6组)。新冠肺炎患者血常规白细胞数量明显升高,血红蛋白平均红细胞体积明显降低。新冠肺炎后患者血小板计数较高,在B1淋巴细胞正常时最高。新冠肺炎患者和正常B1淋巴细胞中单核细胞数量最多,第4组患者单核细胞含量最少。在未感染COVID-19的个体中观察到的粒细胞数量最多,B1淋巴细胞减少。2组患者血小板密度最高。有COVID-19病史和B1淋巴细胞升高的个体嗜中性粒细胞吞噬活性和强度较低。无COVID-19的患者B1淋巴细胞低,嗜中性粒细胞的吞噬数量最少。自发性HBT活性在B1淋巴细胞高且有COVID-19病史的个体中最高,在B1淋巴细胞低且有COVID-19病史的个体中最低。NBT自发指数也以第三组患者最高。第1组观察到nbt诱导的最小活性和指数。1组和2组患者最为严重。1组50%患者诊断为急性心肌梗死,2例患者诊断为支架血栓形成,4例患者死亡。在B1细胞含量正常且有COVID-19病史的患者中,2例死亡,2例发生支架血栓,65%发生急性心肌梗死。这些组自发和诱导的血小板水平较高,HBT活性较低。 在急性冠状动脉综合征合并COVID-19病史的患者中,与无COVID-19病史的患者相比,白细胞、血小板数量增加,中性粒细胞吞噬活性和强度下降,自发和受刺激的NBT活性下降,其中以B1淋巴细胞低的患者最为明显。临床重症患者以感染COVID-19且B1淋巴细胞低的人群最多。
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引用次数: 0
Clinical and immunological efficacy of intranasal interferon in the post-vaccination period in patients vaccinated against SARS-CoV-2 coronavirus 鼻内干扰素在SARS-CoV-2冠状病毒疫苗接种后的临床和免疫效果
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-14715-cai
T. V. Savin, T. O. Tyurina, A. M. Milichkina, I. V. Drozd, Raisa N. Kuznetsova, A. S. Simbirtsev, Areg A. Totolyan
The COVID-19 pandemic, caused by SARS-CoV-2, remains one of the actual medico-social issues of today's world. Novel coronavirus infection officially listed in dangerous infections. When an ingress of coronavirus infection in the background of intensive production of inflammatory inducers comes with decreased levels of type I interferon that cause loss of protective abilities of the body against the background of the destruction of its own tissues. Herd immunity development via vaccination increases the proportion of people with protective immunity against SARS-CoV-2 is an important factor in stopping the spread of the infection. However, during the first days after vaccination, patients remain susceptible to possible infection. A promising prophylactic agent is interferon-containing drugs widely used in Russia and CIS countries for the prevention and treatment of viral infectious diseases, in particular SARS and influenza. Our study showed that intranasal recombinant IFN-2b has clinical and immunological efficacy after two courses of the drug (within 5 days after V1 and after V2 vaccination with the EpiVacCorona vaccine).
由SARS-CoV-2引起的COVID-19大流行仍然是当今世界现实的医学社会问题之一。新型冠状病毒感染被正式列入危险感染。在炎症诱导剂大量产生的背景下,冠状病毒感染的进入伴随着I型干扰素水平的下降,导致身体在自身组织破坏的背景下失去保护能力。通过接种疫苗形成的群体免疫增加了对SARS-CoV-2具有保护性免疫的人群比例,这是阻止感染传播的一个重要因素。然而,在接种疫苗后的头几天,患者仍然容易受到可能的感染。含有干扰素的药物是一种很有前景的预防剂,在俄罗斯和独联体国家广泛用于预防和治疗病毒性传染病,特别是非典型肺炎和流感。我们的研究表明,经2个疗程(V1疫苗接种后5天内和V2疫苗接种后5天内)鼻内重组IFN-2b具有临床和免疫效果。
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引用次数: 0
Differences in the skin microbiota spectrum and parameters of local immunity in the areas of inflammation in skin diseases and healthy people 皮肤病和健康人炎症区皮肤微生物群谱和局部免疫参数的差异
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13086-dit
S. V. Sennikova, Anna P. Toptygina, E. A. Voropaeva
Alteration of microbiota composition is a trigger, and, sometimes, an etiological factor in the development of chronic skin diseases, e.g., psoriasis or eczema. Recognition of microflora by keratinocytes and immune cells leads to the production of antimicrobial peptides, chemokines and growth factors, which contribute to the differentiation of T lymphocytes to autoaggressive effector cells of Th1, Th17 and Th22 types that implement autoimmune inflammation in the psoriatic plaque. The aim of our work was to study the differences in the skin microbiota spectrum and the parameters of local immunity in capillary blood taken near the focus of inflammation in patients with autoimmune (psoriasis) and allergic (eczema) diseases compared with the parameters of healthy people. 24 patients with psoriasis (group 1), 20 patients with eczema (group 2) and 20 healthy adults (group 3) were examined. Biological materials were taken, i.e., the smears taken with sterile dry swab to the Amies transport medium with activated carbon, and capillary blood was taken in 2 microvets, 200 L each) from the foci of inflammation on affected skin from the hands of patients, or from the fingers of healthy people. Inoculations of diagnostic media, microscopy with Gram staining and microbial identification were performed in a microbiological analyzer. Immunophenotyping of 22 subsets of mononuclear cells was performed by four-color staining of capillary blood with erythrocyte lysis and evaluation of subsets by a flow cytometer. Cytokines in blood plasma were determined by multiplex method. The spectrum of hand skin microflora of the group 3 was more diverse in the species composition. In patients with psoriasis and eczema, the coccal flora dominated, with a shift towards pathobionts in the microbiota spectrum. Activation of T and B cells, production of pro-inflammatory cytokines, IL-23/IL-17/IL-22 axis cytokines and cytokines markers of epithelial cell damage (IL-25 and IL-33), as well as anti-inflammatory factors insufficiency were detected. Differences in changing parameters of the local immune status in patients with autoimmune (psoriasis) and allergic (eczema) diseases were revealed, thus reflecting the distinct features of immunopathogenesis in these diseases.
微生物群组成的改变是慢性皮肤病(如牛皮癣或湿疹)发生的触发因素,有时也是病因学因素。角质形成细胞和免疫细胞对微生物菌群的识别导致抗菌肽、趋化因子和生长因子的产生,这有助于T淋巴细胞分化为Th1、Th17和Th22型的自身攻击效应细胞,在银屑病斑块中实施自身免疫性炎症。我们的工作目的是研究自身免疫性(牛皮癣)和过敏性(湿疹)疾病患者在炎症病灶附近采集的毛细血管血液中皮肤微生物群谱和局部免疫参数与健康人群参数的差异。选取银屑病患者24例(第一组),湿疹患者20例(第二组),健康成人20例(第三组)。取生物材料,即用无菌干拭子将涂片取到带活性炭的Amies运输介质中,并从患者的手上或健康人的手指患处皮肤的炎症灶上取毛细血管血(2个微皿,每个200 L)。在微生物分析仪中接种诊断培养基,革兰氏染色显微镜和微生物鉴定。采用毛细管血红细胞溶解四色染色和流式细胞仪对22个单核细胞亚群进行免疫分型。采用多元法测定血浆细胞因子。3组手皮肤菌群的种类组成更为多样化。在牛皮癣和湿疹患者中,球菌菌群占主导地位,在微生物群谱中向病原体转移。检测T细胞和B细胞的活化,促炎细胞因子、IL-23/IL-17/IL-22轴细胞因子和上皮细胞损伤细胞因子标志物(IL-25和IL-33)的产生,以及抗炎因子的不足。揭示了自身免疫性疾病(银屑病)和变应性疾病(湿疹)患者局部免疫状态变化参数的差异,从而反映了这两种疾病免疫发病机制的不同特点。
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引用次数: 0
Analysis of regulatory T lymphocytes in patients with traumatic brain injury 外伤性脑损伤患者调节性T淋巴细胞的分析
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13981-aor
Anna O. Norka, S. V. Vorobyev, R. N. Kuznetsova, M. K. Serebriakova, I V. Kudryavtsev, S. N. Kovalenko, D. N. Monashenko
In recent years, traumatic brain injury (TBI) has been one of the most urgent medical and social problems due to its prevalence, predominantly affecting young people of working age, causing high mortality, disability and economic costs for treatment and subsequent rehabilitation of patients. At present, the role of patients immune system in evolving neuroinflammation after traumatic brain injury has been proven. Treg cell populations represent an important factor determining the outcome of the disease due to promoting induction of immunological tolerance, being a significant component of immunoregulation. As a result of our study, we found a decrease in the relative content of Treg within the total lymphocyte pool of peripheral blood, which has the CD3+CD4+CD25bright phenotype in patients of the 3rd and 4th groups, in comparison with the data from control group. Moreover, a decreased relative content of Tregs (CD4+CD25+T cells) was revealed which is due to the degree of brain tissue damage and, as a result, their migration to suppress inflammation due to production of anti-inflammatory cytokines (TGF-, IL-10). The Treg population is heterogeneous, thus prompting us for analysis of the Treg subpopulations profile based on the expression of CD45R0 and CD62L. When assessing subpopulations of regulatory T lymphocytes within CD45Ro and CD62L, significant changes were found only in patients with brain contusion. The changes were revealed within the pool of naive T regulatory lymphocytes with the CD3+CD4+CD25brightCD39+ Treg phenotype, capable of producing a wide range of cytokines specific for Th1, Th2, Th17, in patients with mild, moderate and severe TBI. Meanwhile, the level of highly active CD3+CD4+CD25brightCD73+ Tregs was significantly reduced in patients with moderate and severe TBI. These changes indicate an imbalance in immunoregulatory processes resulting from extensive damage to brain tissues.
近年来,创伤性脑损伤(TBI)因其普遍性而成为最紧迫的医疗和社会问题之一,主要影响到工作年龄的年轻人,造成高死亡率、残疾和患者治疗和随后康复的经济成本。目前,患者免疫系统在创伤性脑损伤后神经炎症发展中的作用已经得到证实。Treg细胞群是决定疾病结局的重要因素,因为它促进了免疫耐受的诱导,是免疫调节的重要组成部分。我们的研究发现,与对照组相比,第3组和第4组患者外周血中CD3+CD4+CD25bright表型的总淋巴细胞池中Treg的相对含量有所下降。此外,我们还发现Tregs (CD4+CD25+T细胞)的相对含量降低,这是由于脑组织损伤程度所致,因此它们通过产生抗炎细胞因子(TGF-, IL-10)而迁移到抑制炎症。Treg群体是异质的,因此促使我们基于CD45R0和CD62L的表达分析Treg亚群体的概况。当评估CD45Ro和CD62L内调节性T淋巴细胞亚群时,仅在脑挫伤患者中发现显著变化。在轻度、中度和重度TBI患者中,CD3+CD4+CD25brightCD39+ Treg表型的幼稚T调节性淋巴细胞池中发现了这些变化,这些淋巴细胞能够产生广泛的Th1、Th2、Th17特异性细胞因子。同时,中重度TBI患者的高活性CD3+CD4+CD25brightCD73+ Tregs水平显著降低。这些变化表明免疫调节过程的不平衡是由脑组织的广泛损伤引起的。
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引用次数: 0
Expression of “non-classical” molecules of the main histocompatibility complex in rheumatoid arthritis and bronchial asthma 主要组织相容性复合体“非经典”分子在类风湿关节炎和支气管哮喘中的表达
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13919-eon
Olga S. Boeva, V. I. Borisevich, V. A. Kozlov, D. V. Vladimirovna, A. E. Sizikov, E. A. Pashkina
HLA-E is a minor understudied non-classical HLA genes. HLA-E transcription is revealed in many cell types, especially, in immune cells, e.g., T and B cells monocytes, macrophages. In this work, we evaluated expression of HLA-E on CD8+, CD4+ and CD14+ cells in conditionallу healthy donors and in the patients with bronchial asthma (BA) and rheumatoid arthritis (RA). Peripheral blood mononuclears (PBMNC) were used as initial biomaterial. PBMNC from RA patients (n = 15), BA (n = 11) and healthy donors were separated from peripheral blood in Ficoll-Urographin density gradient (1.077 g/mL). The cells were then stained with fluorochrome-conjugated monoclonal antibodies: anti-CD3-APC, anti-CD4-APC-Cy7, anti-CD-14-FITC, and anti-HLA-E-PerCP/Cy5. The cell phenotype was analyzed by flow cytometry with FACS Canto II (BD Biosciences, USA). We have found an increased expression of HLA-E on CD8+, CD4+Т cells, like as on CD14+ cells (monocytes) in the RA patients, when compared with BA patients. We have also shown significant differences of HLA-E expression on CD8+Т cells between the conditionally healthy donors and RA patients.
HLA- e是一个次要的未被充分研究的非经典HLA基因。HLA-E转录在许多细胞类型中发现,特别是在免疫细胞中,如T细胞和B细胞、单核细胞、巨噬细胞。在这项工作中,我们评估了HLA-E在条件健康供体和支气管哮喘(BA)和类风湿性关节炎(RA)患者的CD8+、CD4+和CD14+细胞上的表达。外周血单核细胞(PBMNC)作为初始生物材料。以Ficoll-Urographin密度梯度(1.077 g/mL)从外周血中分离RA患者(15例)、BA患者(11例)和健康献血者的PBMNC。然后用荧光染料偶联的单克隆抗体:抗cd3 - apc、抗cd4 - apc - cy7、抗cd -14- fitc和抗hla - e- percp /Cy5对细胞进行染色。流式细胞术分析细胞表型,使用FACS Canto II (BD Biosciences, USA)。我们发现,与BA患者相比,RA患者的CD8+、CD4+Т细胞上的HLA-E表达增加,与CD14+细胞(单核细胞)上的表达一样。我们还发现,在条件健康供者和RA患者之间,CD8+Т细胞上HLA-E的表达有显著差异。
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引用次数: 0
Role of NLRP3 in the immunopathogenesis of neurodegenerative eye diseases NLRP3在神经退行性眼病免疫发病机制中的作用
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13985-ron
N. V. Balatskaya, T. V. Gavrilova, Aliya R. Kinkulkina, A. S. Avagyan, O. A. Svitich
Neurodegenerative eye pathology is one of the leading causes of visual impairment and blindness worldwide. Primary open-angle glaucoma (POAG) belongs to the group of neurodegenerative ophthalmic diseases and is characterized by a permanent or periodic increase in intraocular pressure, followed by development of typical visual field defects, decreased visual acuity and optic nerve atrophy. Recent studies show that local inflammation, triggered by the innate immune system is the first line of defense against the pathogens and tissue destruction products, playing an important role in the POAG pathogenesis. The aim was to study the neurodegenerative ophthalmic disorder in a rabbit model, and to compare the data on distribution of alleles and genotypes of the polymorphic marker rs7525979 of NLRP3 gene in the patients with POAG. At the first stage, we studied the complex tissue samples of the retina/retinal pigment epithelium (TCS/RPE) isolated from the eyes of 14 experimental animals and 7 intact rabbits without eye damage. Neurodegenerative pathology of the eye in rabbits was carried out in the Experimental Center at the Helmholtz National Medical Research Center by a single subretinal injection of 0.01 ml of 0.9% sodium chloride solution. NLRP3 gene expression levels in TCS/RPE samples were evaluated by real-time polymerase chain reaction (PCR-RV). At the second stage, peripheral blood samples were examined in patients who were diagnosed with POAG of various stages, as well as without glaucoma. DNA was isolated from blood samples, which was subsequently analyzed for the polymorphic markers study using PCR-RT technique. According to the results of the study, we noted an increased expression of the NLRP3 gene in the TCS/RPE samples from experimental animals with simulated retinal degeneration. Moreover, an association of alleles and genotypes of the NLRP3 gene was revealed in patients with POAG. The data obtained may be indicative for involvement of NLRP3 inflammasome components in development of neurodegenerative retinal lesions in POAG.
神经退行性眼病理是世界范围内视力损害和失明的主要原因之一。原发性开角型青光眼(POAG)属于眼神经退行性疾病,其特点是眼压永久性或周期性升高,随后发展为典型的视野缺损、视力下降和视神经萎缩。近年来的研究表明,先天免疫系统引发的局部炎症是抵御病原体和组织破坏产物的第一道防线,在POAG的发病机制中起着重要作用。目的研究兔神经退行性眼病模型,比较POAG患者NLRP3基因多态性标记rs7525979等位基因分布和基因型数据。在第一阶段,我们研究了从14只实验动物和7只眼睛未损伤的完整兔子的眼睛中分离的视网膜/视网膜色素上皮(TCS/RPE)的复杂组织样本。在Helmholtz国家医学研究中心实验中心,通过单次在视网膜下注射0.01 ml 0.9%氯化钠溶液进行家兔眼部神经退行性病理研究。采用实时聚合酶链反应(real-time polymerase chain reaction, PCR-RV)检测NLRP3基因在TCS/RPE中的表达水平。在第二阶段,检查了诊断为不同阶段POAG的患者的外周血样本,以及没有青光眼的患者。从血液样本中分离DNA,随后使用PCR-RT技术对其进行多态性标记研究分析。根据研究结果,我们注意到在模拟视网膜变性实验动物的TCS/RPE样本中NLRP3基因的表达增加。此外,在POAG患者中发现了NLRP3基因的等位基因和基因型的关联。所获得的数据可能指示NLRP3炎性体成分参与POAG神经退行性视网膜病变的发展。
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Russian journal of immunology : RJI : official journal of Russian Society of Immunology
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