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Levels of TREC and KREC molecules significance determining in peripheral blood for predicting the outcome of COVID-19 disease in the acute period 外周血TREC和KREC分子水平对预测COVID-19急性期预后的意义
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-14714-lot
Maria A. Saitgalina, Yu. V. Ostankova, N. A. Arsentieva, Z. R. Korobova, N. E. Liubimova, V. A. Kashchenko, A. N. Kulikov, D. E. Pevtsov, O. V. Stanevich, E. I. Chernykh, Areg A. Totolian
The disease caused by the highly contagious SARS-CoV-2 virus novel coronavirus infection (COVID-19) had killed more than 6.5 million people at the end of December 2022. The severity of the manifestation of the infectious process varies from asymptomatic forms to rapid progression to life-threatening conditions requiring emergency measures. One of the factors, the severity of which affects the outcome of the disease, is lymphopenia, the cause of which may be a violation of lymphopoiesis. The identification of laboratory markers of a high risk of mortality in patients with COVID-19 plays an important role in improving patient care algorithms and increasing their survival. Levels of TREC and KREC molecules in peripheral blood, respectively, can serve as molecular markers of the severity of T and B lymphopenias. The aim of our work was a comparative analysis of the levels of TREC and KREC molecules in the peripheral blood of surviving and deceased patients with COVID-19. The material was whole blood samples obtained from 1745 people, including: 1028 patients diagnosed with novel coronavirus infection (COVID-19) (ICD-10 code U07.1), of which 937 patients recovered and 91 died; 717 apparently healthy individuals (control group). The levels of TREC and KREC molecules were assessed by quantitative multiplex Real-time PCR using the TREC/KREC-AMP PS reagent kit (Federal Scientific Research Institute Pasteur, St. Petersburg). Statistically significant differences in the levels of KREC and TREC molecules between the control group and patients, both surviving and deceased, were established. A significant decrease in median concentrations of KREC molecules was shown in patients with a lethal outcome compared with survivors (p = 0.0019, 95% CI). Among the deceased patients, in 63.7% of cases, the levels of TREC or KREC molecules were reduced relative to the corresponding age norms. Of these, in 20.9% of cases, both analytes were reduced in patients. When assessing the diagnostic significance of the levels of the analytes under study for predicting the outcome of the disease, the area under the AUC curve for KREC was 0.630.029, which indicates the average strength of the prognostic model of the patient's death depending on the level of KREC in the blood. The constructed model is statistically significant (p = 0.002). Monitoring laboratory parameters of patients with COVID-19, including those who died, allows you to determine the prognostic factors that are most significant for assessing the outcome of the disease. Based on the assessment of the KREC level, a predictive model with high specificity reflects the risk of death in patients with COVID-19. Thus, the quantitative determination of the level of KREC molecules in the peripheral blood can be attributed to the methods of preventive personalized diagnostics aimed at improving the survival of patients.
截至2022年12月底,由高度传染性的SARS-CoV-2病毒引起的新型冠状病毒感染(COVID-19)已造成650多万人死亡。感染过程表现的严重程度各不相同,从无症状形式到迅速进展到需要采取紧急措施的危及生命的情况。其中一个因素是淋巴细胞减少,其严重程度影响疾病的结果,其原因可能是淋巴细胞生成的破坏。识别COVID-19患者死亡高风险的实验室标志物对改进患者护理算法和提高患者生存率具有重要作用。外周血中TREC和KREC分子水平分别可作为T淋巴细胞减少症和B淋巴细胞减少症严重程度的分子标志物。我们的工作目的是比较分析存活和死亡的COVID-19患者外周血中TREC和KREC分子的水平。材料为取自1745人的全血样本,包括:确诊为新型冠状病毒感染(COVID-19) (ICD-10代码U07.1)的患者1028例,其中937例康复,91例死亡;717例明显健康个体(对照组)。采用TREC/KREC- amp PS试剂盒(圣彼得堡巴斯德联邦科学研究所),采用多重实时荧光定量PCR检测TREC和KREC分子水平。在对照组和患者(包括存活患者和死亡患者)之间,KREC和TREC分子水平的差异具有统计学意义。与幸存者相比,致命结局患者的KREC分子中位浓度显著降低(p = 0.0019, 95% CI)。在死亡患者中,63.7%的病例TREC或KREC分子水平相对于相应的年龄标准降低。其中,在20.9%的病例中,两种分析物在患者中都减少了。在评估所研究的分析物水平对预测疾病结局的诊断意义时,KREC的AUC曲线下面积为0.630.029,这表明患者死亡预测模型依赖于血液中KREC水平的平均强度。构建的模型具有统计学意义(p = 0.002)。监测COVID-19患者(包括已死亡患者)的实验室参数,可使您确定对评估疾病结果最重要的预后因素。基于对KREC水平的评估,一个高特异性的预测模型可以反映COVID-19患者的死亡风险。因此,外周血中KREC分子水平的定量测定可归因于旨在提高患者生存率的预防性个性化诊断方法。
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引用次数: 1
Indices of cellular and humoral immunity in a patient with a history of central precocious puberty in anamnesis 失忆症中枢性性早熟患者的细胞和体液免疫指标
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13906-ioc
Diliara R. Khisamutdinova, Ya. I. Kozlova, E. B. Башнина, E. V. Frolova, A. E. Uchevatkina, L. V. Filippova, N. V. Vasilyeva
The etiology of precocious puberty includes organic anomalies, genetic mutations, but the primary cause remains unclear in the vast majority of cases. Gonadotropin-releasing hormone (GRH) agonists are used as a treatment of gonadotropin-dependent precocious puberty. Blocking the secretion of gonadotropin-releasing hormone, these drugs stop the premature development of sexual features, prevent premature closure of ossification zones, thereby increasing the childs expected adult height. The interest in the effects of this group of drugs beyond the hypothalamic-pituitary-gonadal axis has been recently increased. A series of clinical cases have been reported on the development of autoimmune diseases, e.g., autoimmune thyroiditis, Graves disease and type 1 diabetes. The article presents a clinical observation of a patient with central form of premature development who exhibited satisfactory response to treatment with a GRH agonist drug. Further follow-up did not show any reproductive dysfunction. Upon immunological examination, a disturbance was revealed only in the cellular component of immunity. An increased metabolic activity of neutrophils was found, thus, probably, indicating a nonspecific inflammatory process. The levels of immunoglobulins A, M, G matched the reference values. Thus, the therapy with a drug from the group of GRH agonists was effective and safe in terms of influencing the patients immune system. The role of hormonal disorders and effects of GRH agonists on the development of immunopathological conditions require further research.
性早熟的病因包括器质性异常、基因突变,但绝大多数病例的主要病因尚不清楚。促性腺激素释放激素(GRH)激动剂被用作治疗促性腺激素依赖性性早熟。这些药物阻断促性腺激素释放激素的分泌,阻止性特征的过早发育,防止骨化区过早闭合,从而增加孩子成年后的预期身高。对这组药物在下丘脑-垂体-性腺轴以外的作用的兴趣最近有所增加。已报道了一系列自身免疫性疾病的临床病例,如自身免疫性甲状腺炎、Graves病和1型糖尿病。这篇文章提出了一个临床观察的病人与中心形式的过早发展,谁表现出满意的反应与治疗的GRH激动剂药物。进一步随访未发现任何生殖功能障碍。经免疫学检查,只发现免疫的细胞成分受到干扰。发现中性粒细胞代谢活性增加,因此,可能表明非特异性炎症过程。免疫球蛋白A、M、G与参考值相符。因此,就影响患者的免疫系统而言,使用GRH激动剂组中的一种药物治疗是有效和安全的。激素紊乱和GRH激动剂在免疫病理条件发展中的作用有待进一步研究。
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引用次数: 0
Mucosal humoral immune response of respiratory tract in medical workers during the post-COVID-19 period 新冠肺炎疫情后医务人员呼吸道黏膜体液免疫反应
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13921-mhi
N. O. Kryukova, Albina А. Khasanova, I. A. Baranova, M. P. Kostinov, O. A. Svitich, A. G. Chuchalin
Currently, the role of local respiratory tract immunoglobulins in COVID-19 and rearrangement of mucosal immune response in the post-COVID period have not been sufficiently studied. Our aim was to evaluate long-term effects of novel coronavirus infection on the mucosal immunity in healthcare workers over the post-infection period. A total of 180 healthcare workers, ranging in age from 18 to 65 years, were enrolled in a one-stage, cross-sectional study. The subjects with a history of COVID-19 were divided into three groups, depending on the severity of their disease. The control group consisted of 44 healthcare workers who had no history of novel coronavirus infection. Secretory immunoglobulin A (sIgA) and total immunoglobulin G (IgG) levels were quantified in saliva samples, induced sputum samples, naso- and oropharyngeal scrapings by ELISA technique. Specific anti-SARS-CoV-2 IgG antibodies were quantified in the serum by chemiluminescence immunoassay. Numerous shifts in adaptive immune response were detected for different mucosal compartments, i.e., in subjects who suffered from severe or moderate-to-severe COVID-19, salivary sIgA levels were significantly higher than those in the control group (p 0.05 and p 0.005, respectively). An inverse correlation was demonstrated between the levels of total sIgA in all mucosal sites, and the number of days from the onset of disease to the start of study (r = 0.278, р 0.05). When compared to the control subjects, all the patients with prior COVID-19 had significantly higher levels of total IgG in the induced sputum samples. Total IgG in saliva was also higher in the group of patients who had severe infection (p 0.05). By contrast, IgG levels in nasopharyngeal samples were decreased in severe and moderately severe groups compared to the control group, thus, probably, indicating an immunodeficiency state in these cases. A direct significant correlation was also detected between the levels of total IgG in all studied samples and the levels of specific IgG antibodies against SARS-CoV-2 in the serum. Long-term changes in the humoral mucosal immune response were most pronounced in the healthcare workers with a history of severe or moderate-to-severe COVID-19.
目前,局部呼吸道免疫球蛋白在COVID-19中的作用以及COVID-19后黏膜免疫应答重排的研究尚不充分。我们的目的是评估新型冠状病毒感染对医护人员感染后黏膜免疫的长期影响。共有180名年龄在18岁至65岁之间的卫生保健工作者参加了一项单阶段横断面研究。有COVID-19病史的受试者根据疾病的严重程度分为三组。对照组为44名无新型冠状病毒感染史的医护人员。采用ELISA法定量测定唾液、诱导痰、鼻咽刮痕中分泌性免疫球蛋白A (sIgA)和总免疫球蛋白G (IgG)水平。化学发光免疫法测定血清中特异性抗sars - cov -2 IgG抗体。 在不同的粘膜区室中检测到许多适应性免疫反应的变化,即在患有严重或中重度COVID-19的受试者中,唾液sIgA水平显著高于对照组(分别为p 0.05和p 0.005)。所有粘膜部位的总sIgA水平与发病至研究开始的天数呈负相关(r = 0.278, 0.05)。与对照组相比,所有既往感染COVID-19的患者诱导痰样本中总IgG水平均显著升高。严重感染组唾液中IgG总含量明显高于对照组(p < 0.05)。相比之下,与对照组相比,严重和中度严重组鼻咽样本中的IgG水平降低,因此,可能表明这些病例存在免疫缺陷状态。所有研究样本中总IgG水平与血清中抗SARS-CoV-2特异性IgG抗体水平之间也存在直接显著相关。 在有严重或中重度COVID-19病史的医护人员中,体液粘膜免疫反应的长期变化最为明显。
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引用次数: 0
Single nucleotide polymorphism of osteoprotegerin as a possible biomarker of rheumatoid arthritis in Bashkir population of Chelyabinsk region 车里雅宾斯克地区巴什基尔人群中骨保护素单核苷酸多态性作为类风湿关节炎可能的生物标志物
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13964-snp
Yu. V. Chumacheva, Darya S. Stashkevich, I. V. Devald, T. A. Suslova
Rheumatoid arthritis (RA) is a multifactorial autoimmune rheumatic disease of unknown etiology characterized by chronic erosive arthritis. The protein osteoprotegerin (OPG) is a member of bone tissue homeostasis (RANK/RANKL/OPG) which is responsible for the regulation of osteoclast differentiation and osteolysis. The altered binding of RANKL and OPG is one of the causes of many diseases with increased production of pro-inflammatory cytokines, including rheumatoid arthritis. Polymorphic variants of the genes that control protective reactions could affect the level of production for encoded proteins and, thus, changing the course of immune response in RA. G1181C SNP in osteoprotegerin gene leads to disruption of its transcriptional activity and conformation of the protein itself, which can lead to an imbalance of pro- and anti-inflammatory cytokines. We analyzed the relationship between the TNFRSF11B gene polymorphism at the 1181 G C position and the risk of developing RA in the Bashkir population. The analysis was based on a molecular genetic study of single nucleotide polymorphism in groups of patients with rheumatoid arthritis and conditionally healthy individuals of the Bashkir population of the Chelyabinsk Region. Statistical evaluation was carried out using standard criteria generally accepted in immunogenetics. The 1181*GC polymorphism of the osteoprotegerin gene is characterized by interpopulation differences, which confirms the importance of using an ethnically identical comparison group to assess the association with a predisposition to multifactorial pathology. We showed that the carriage of genotype 1181 G/C was increased in the group of Bashkirs with rheumatoid arthritis. This genotype could be considered a biomarker of susceptibility to RA. No differences in the SNP allelic frequencies and genotypes were found among women with RA. Our research is a part of comprehensive assessment of the interaction of cytokines and their receptors from the TNFsuperfamily as an immunogenetic component of RA genesis.
类风湿性关节炎(RA)是一种病因不明的多因素自身免疫性风湿性疾病,以慢性糜烂性关节炎为特征。骨保护蛋白(OPG)是骨组织稳态(RANK/RANKL/OPG)的一员,负责调节破骨细胞分化和骨溶解。RANKL和OPG结合的改变是许多促炎细胞因子产生增加的疾病的原因之一,包括类风湿性关节炎。控制保护反应的基因的多态性变异可能影响编码蛋白的产生水平,从而改变类风湿关节炎的免疫反应过程。骨保护素基因中的G1181C SNP导致其转录活性和蛋白质本身构象的破坏,从而导致促炎和抗炎细胞因子的失衡。我们分析了巴什基尔人群中1181 G C位点TNFRSF11B基因多态性与RA发病风险之间的关系。该分析是基于对车里雅宾斯克地区巴什基尔人群中类风湿关节炎患者和条件健康个体的单核苷酸多态性的分子遗传学研究。采用免疫遗传学普遍接受的标准进行统计评价。骨保护素基因的1181*GC多态性具有种群间差异的特征,这证实了使用种族相同的对照组来评估其与多因素病理易感性的相关性的重要性。我们发现基因型1181 G/C的携带在类风湿关节炎的巴什基尔人组中增加。该基因型可被认为是RA易感性的生物标志物。在类风湿关节炎女性患者中,SNP等位基因频率和基因型没有差异。我们的研究是对tnf超家族细胞因子及其受体相互作用作为RA发生的免疫遗传成分的综合评估的一部分。
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引用次数: 0
Immunological and biochemical markers of adverse outcome in COVID-19 and arterial hypertension COVID-19与动脉性高血压不良结局的免疫学和生化指标
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13945-iab
Anna V. Mordyk, N. V. Bagisheva, M. V. Moiseeva, E. P. Antipova, V. V. Streltsova
Coronavirus is able to affect various organs and systems including the immune system. At the same time, the state of the immune system may be initially changed in patients with pre-existing comorbid non-infectious disorders. The aim of our study was to evaluate biochemical and immunological markers of adverse outcomes in the patients with new coronavirus infection with underlying arterial hypertension. The retrospective study included 47 patients with COVID-19 and arterial hypertension, who underwent a study of C-reactive protein (CRP), interleukin-6 (IL-6), assessing the increased values of these markers and the outcomes of the disease. The study group included 23 male and 24 female patients at the median age of 54 (for men), and 57 years old (for women). Upon admittance of the patients with COVID-19 and hypertension to the hospital, a parallel increase in both CRP and IL-6 was registered in these cases. Statistically significant differences were found in the levels of CRP and IL-6 in patients with a favorable versus unfavorable clinical outcomes. The levels of CRP and IL-6 in deceased patients were higher and did not tend to decrease. Thus, the simultaneous increase in CRP and IL-6 in patients with COVID-19 and hypertension is considered an unfavorable prognostic parameter for patients survival.
冠状病毒能够影响包括免疫系统在内的各种器官和系统。与此同时,免疫系统的状态可能会在已有合并症的非感染性疾病患者中发生最初的改变。本研究的目的是评价新型冠状病毒感染合并潜在动脉高血压患者不良结局的生化和免疫学指标。这项回顾性研究包括47例COVID-19合并动脉性高血压患者,他们接受了c反应蛋白(CRP)、白细胞介素-6 (IL-6)的研究,评估这些标志物的升高值和疾病的结局。研究组包括23名男性和24名女性患者,中位年龄为54岁(男性),中位年龄为57岁(女性)。在新冠肺炎合并高血压患者入院时,这些病例的CRP和IL-6均平行升高。在临床结果良好与不良的患者中,CRP和IL-6水平存在统计学上的显著差异。死亡患者CRP和IL-6水平较高且无下降趋势。因此,COVID-19合并高血压患者CRP和IL-6同时升高被认为是患者生存的不利预后参数。
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引用次数: 0
Therapeutic effect of a new immunotropic composition tested in the model of periodontitis in experimental animals 一种新的免疫组合物在实验动物牙周炎模型上的治疗效果
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13532-teo
K. A. Khlystova, N. S. Chumakov, N. G. Sarkisyan, Natalia N. Kataeva, L. I. Drozdova, I. A. Tuzankina
The article deals with usage of a novel immunotropic drug composition in experimental model of periodontitis. The composition contains silicoorganic glycerogel, exhibits broad spectrum of action upon the etiological pathogen. A good therapeutic effect was revealed by clinical, laboratory and histological criteria. Histology showed absence of osteoclasts, reduced lacunas, higher density and normalization of tissue structures, recovery of microcirculation, angiogenesis and formation of granulation tissues. However, the phosphorus-to-calcium ratio in the group supplied with peroral vitamin D treatment, was characterized by significant decrease in alkaline phosphatase and inorganic phosphorus thus confirming efficiency of complex topical effect of the given composition and vitamin D.
本文讨论了一种新型免疫药物组合物在牙周炎实验模型中的应用。该组合物含有有机硅甘油凝胶,对病原菌具有广谱作用。临床、实验室及组织学指标均显示治疗效果良好。组织学显示破骨细胞缺失,腔隙缩小,组织结构密度增大,组织结构正常化,微循环恢复,血管新生,肉芽组织形成。然而,在口服维生素D治疗组,磷钙比的特点是碱性磷酸酶和无机磷显著降低,从而证实了给定组合物和维生素D的复合局部作用的效率。
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引用次数: 0
Clinical and immunological efficacy of the immunomodulating hexapeptide arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine in the complex postoperative treatment of children with acute osteomyelitis 免疫调节六肽精氨酸- α -天冬氨酸-赖氨酸-缬氨酸-酪氨酸-精氨酸在小儿急性骨髓炎术后复杂治疗中的临床及免疫学疗效
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13763-cai
Galina A. Chudilova, E. A. Chicherev, Yu. V. Teterin, V. N. Chapurina, V. A. Tarakanov, N. K. Barova, I. V. Nesterova
The recurrent and persistent nature of osteomyelitis, like as associated high morbidity of patients, prolonged hospitalization and expensive treatment require development of new approaches in therapy and pathogenetic justification of the immunotropic drugs usage in complex etiopathogenetic treatment of this disorder. Our objective was to evaluate the clinical and immunological efficacy of hexapeptide (HP), arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine implemented in the complex treatment of acute osteomyelitis in children during the postoperative period. 19 children aged 8-15 years with acute osteomyelitis (AOM) were studied: the study group 1 (SG1, n = 11) received a standard treatment at all the disease stages; in study group 2 (SG2, n = 8), the standard therapy was supplemented with a medical drug Imunofan, containing hexapeptide (НP) as the active substance. Prior and after the course of drug treatment, we determined the following parameters: the contents of T cells (CD3+CD19-, CD3+CD4+, CD3+CD8+, CD3+CD4+/CD3+CD8+) and B cells (CD3-CD19+), NK (CD3-CD16+CD56+) by means of Cytomics FC-500 (Веckman Coulter, USA), the levels of serum IgA, IgM, IgG (ELISA tests), assessment of phagocytic activity of neutrophil granulocytes (NG) with determining the ratio of actively phagocytic NG (%PhAN), capture processes (PhN, PhI) and the completeness of phagocytosis (%D, DI) tested with S. aureus (strain No. 209). In the studied groups with AOM, a decreased content of T lymphocytes, T helper cells, T lymphocytes, NK cells was revealed, along with unchanged content of B lymphocytes. In SG2, the increased IgA and IgG levesl have been shown. We have also revealed a deficiency of phagocytic function associated with the processes of phagocytosis completion. The use of immunomodulatory therapy with an HP-containing pharmaceutical drug in combination with standard treatment was associated with restoration of immunological parameters to the reference values of healthy children, thus leading to shorter febrile period, milder manifestations of intoxication, earlier periods of reconvalescence from purulent-inflammatory process, and reduced hospital stay. The obtained positive clinical and immunological effects demonstrate the expediency of targeted immunomodulatory therapy including a pharmaceutical HP-containing drug as the active substance in the complex postoperative treatment of children with AOM. Restoration of the disturbed mechanisms of anti-infectious immunity in AOM under usage of immunomodulating HP contributes to more effective elimination of pathogens and, as a result, improvement of the clinical course of the disease, as well as prevention of chronic inflammatory processes and aggravation of immune system dysfunction.
骨髓炎的复发性和持续性,如相关患者的高发病率、长期住院和昂贵的治疗,需要开发新的治疗方法和在复杂的病因学治疗中使用免疫药物的病理合理性。我们的目的是评估六肽(HP),精氨酸- α -天冬氨酸-赖氨酸-缬氨酸-酪氨酸-精氨酸在儿童术后急性骨髓炎综合治疗中的临床和免疫学疗效。研究了19名8-15岁急性骨髓炎(AOM)儿童:研究组1 (SG1, n = 11)在所有疾病阶段接受标准治疗;研究2组(SG2, n = 8)在标准治疗的基础上加用含六肽(НP)为活性物质的医用药物免疫凡。在药物治疗前后,我们确定了以下参数:利用流式细胞仪FC-500 (Веckman Coulter, USA)检测T细胞(CD3+CD19-、CD3+CD4+、CD3+CD8+、CD3+CD4+/CD3+CD8+)和B细胞(CD3-CD19+)、NK细胞(CD3- cd16 +CD56+)的含量,ELISA检测血清IgA、IgM、IgG的水平,用金黄色葡萄球菌(菌株209)检测中性粒细胞(NG)的吞噬活性,测定活性吞噬NG的比例(%PhAN)、捕获过程(PhN、PhI)和吞噬的完整性(%D、DI)。AOM组T淋巴细胞、T辅助细胞、T淋巴细胞、NK细胞含量降低,B淋巴细胞含量不变。在SG2中,IgA和IgG水平升高。我们还揭示了与吞噬完成过程相关的吞噬功能缺陷。采用含hp药物的免疫调节治疗联合标准治疗,可使健康儿童的免疫参数恢复到参考值,从而缩短发热期,减轻中毒症状,提前从脓性炎症过程中恢复,缩短住院时间。所获得的积极的临床和免疫学效果表明,包括含hp药物作为活性物质的靶向免疫调节治疗在AOM患儿复杂的术后治疗中的便宜性。在免疫调节HP的作用下,恢复AOM中被干扰的抗感染免疫机制,有助于更有效地消除病原体,从而改善疾病的临床病程,并预防慢性炎症过程和免疫系统功能障碍的加重。
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引用次数: 0
Time-dependent changes of platelet and D-dimer parameters in vaccinated <i>versus</i> non-immunized COVID-19 patients 免疫组血小板和d -二聚体参数随时间变化的变化&lt;i&gt;未接种COVID-19疫苗的患者
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13983-tdc
M. P. Kostinov, Chen Zhang, I. A. Khrapunova, A. S. Pechenik, V. A. Utkin, M. N. Loktionova, K. V. Mashilov, Irina L. Soloveva
There are increasing data concerning changes in hematological (clinical) and biochemical blood tests in patients with COVID-19 infection, which indicate the severity of the manifestations of the infectious process. Coagulopathy often correlates with the severity of COVID-19 disease and the risk of death. In this regard, prediction of developing coagulopathy and its prevention remain quite relevant. The aim of our study was to identify differences in the content of platelets and D-dimer in patients with COVID-19. The study included cohorts of patients vaccinated against SARS-CoV-2, and those not immunized against this infection. A prospective, randomized, observational study of the patients response was performed in cohorts of 588/52.2% vaccinated (vaccinated) and 588/52.2% non-immunized (non-vaccinated) patients with diagnosed COVID-19 over the period from 23.06.2021 to 01.05.2022. The levels of blood platelets and D-dimer, as well as clinical outcomes of the disease in patients with COVID-19, were studied in dynamics on days 1-2, 5-6 and 10-12 of hospitalization. Upon admission, the normal value of the blood platelet counts did not differ between the compared groups, being 206.58 109 in vaccinated group and 204.85 109 in the unvaccinated group, respectively. a moderate increase in the concentration of D-dimer was noted in both groups upon admission, i.e., 2838.60 ng/mL in the group of vaccinated patients and 3242.08 ng/mL among the unvaccinated patients. In the course of the study, we have shown that the dynamics of D-dimer index in vaccinated versus non-immunized persons was similar according to the days of disease, showing an increase from the first day and a trend towards an higher values, starting from 5-6 days. At the same time, the dynamics in the vaccinated patients was somewhat less favorable than that of the non-immunized subjects. In the patients who were not immunized throughout the entire observation period, the platelet count exceeds the levels found in vaccinated subjects, thus suggesting higher risk of thrombosis and cytokine storm. The data obtained show that the dynamics of D-dimer and platelet counts in vaccinated and non-immunized people is similar on appropriate terms of the illness. However, the changes are more pronounced in vaccinated cohort, but it does not indicate a greater risk of adverse outcomes.
越来越多的数据显示,COVID-19感染患者的血液学(临床)和生化血液检测结果发生了变化,这表明感染过程的表现非常严重。凝血功能障碍通常与COVID-19疾病的严重程度和死亡风险相关。在这方面,预测发展凝血病及其预防仍然是相当相关的。我们研究的目的是确定COVID-19患者血小板和d -二聚体含量的差异。该研究包括接种过SARS-CoV-2疫苗的患者和未接种过这种感染疫苗的患者。在2021年6月23日至2022年1月5日期间,对588/52.2%接种疫苗(已接种)和588/52.2%未接种疫苗(未接种)的确诊COVID-19患者进行了一项前瞻性、随机、观察性研究。动态观察新冠肺炎患者住院后1-2天、5-6天、10-12天的血小板、d -二聚体水平及临床预后。入院时,两组间血小板计数正常值无差异,接种组为206.58 109,未接种组为204.85 109。两组患者入院时d -二聚体浓度均有中度升高,接种组为2838.60 ng/mL,未接种组为3242.08 ng/mL。在研究过程中,我们发现接种疫苗的人与未接种疫苗的人d -二聚体指数的动态根据发病天数是相似的,从第一天开始增加,从5-6天开始有更高的趋势。与此同时,接种疫苗的患者的动态比未接种疫苗的患者稍差。在整个观察期间未接种疫苗的患者中,血小板计数超过接种疫苗的患者,提示血栓形成和细胞因子风暴的风险更高。 所获得的数据表明,在适当的疾病条件下,接种疫苗和未接种疫苗的人的d -二聚体和血小板计数的动态相似。然而,这些变化在接种疫苗的队列中更为明显,但并不表明不良后果的风险更大。
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引用次数: 0
Approaches to correction of immune system disturbances in post-COVID patients 新冠肺炎后患者免疫系统紊乱的纠正方法
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13492-atc
Maria A. Dobrynina, A. V. Zurochka, V. A. Zurochka, L. V. Ryabova, A. P. Sarapultsev
SARS-CoV-2 virus can induce immune system disorders in post-COVID patients, which may persist for an extended period beyond the acute phase of the disease. Therefore, the search for immunocorrection approaches to address the detected disorders is a significant challenge in clinical immunology. This study aimed to investigate the impact of a synthetic peptide derived from the active center of GM-CSF on the immune system of patients with post-COVID immunopathological syndrome. A total of 21 patients who previously suffered with SARS-CoV-2 infection were included in the study. Flow cytometry was used to analyze various immune cell populations, including panleukocyte markers for gated lymphocytes (CD45+ and CD46+), T lymphocytes (CD3+), helper inducers (CD3+, CD4+), cytotoxic T lymphocytes (CD3+, CD8+), TNK cells (CD3+, CD56+), natural killer cells (CD3-, CD56+), B lymphocytes (CD3-, CD19+), activated helper cells (CD3+, CD4+, CD25+), and activated T lymphocytes (CD3+, HLA-DR). Moreover, IgA, IgM, IgG antibodies specific to SARS-CoV-2, phagocytosis and NBT activity of neutrophils, and complement fragments C1q, C3a, and C5a were assessed. The results demonstrated that topical application of the synthetic peptide derived from the active center of GM-CSF (Acegram-spray) upon mucous membranes significantly influenced the functional bactericidal activity of neutrophils (NBT-activity), increased the percentage of T helper cells, and elevated the C3a complement fragment. These findings indicate that the synthetic peptide primarily affects innate immunity factors. However, no significant differences were observed in other immune system parameters. Therefore, the development of therapeutic approaches for post-COVID patients with impaired immune systems may require a search for additional immunomodulators that target T, B, and NK cells. Further research is needed to explore the effects of various immunomodulators on the immune system of post-COVID patients.
SARS-CoV-2病毒可在covid后患者中诱发免疫系统紊乱,这种紊乱可能在疾病急性期之后持续较长时间。因此,寻找免疫矫正方法来解决检测到的疾病是临床免疫学的一个重大挑战。本研究旨在探讨GM-CSF活性中心衍生的合成肽对covid - 19后免疫病理综合征患者免疫系统的影响。共有21名先前患有SARS-CoV-2感染的患者被纳入该研究。用流式细胞术分析各种免疫细胞群,包括门控淋巴细胞(CD45+和CD46+)、T淋巴细胞(CD3+)、辅助诱导剂(CD3+、CD4+)、细胞毒性T淋巴细胞(CD3+、CD8+)、TNK细胞(CD3+、CD56+)、自然杀伤细胞(CD3-、CD56+)、B淋巴细胞(CD3-、CD19+)、活化辅助细胞(CD3+、CD4+、CD25+)和活化T淋巴细胞(CD3+、HLA-DR)的泛白细胞标记物。此外,还评估了SARS-CoV-2特异性IgA、IgM、IgG抗体、中性粒细胞的吞噬和NBT活性以及补体片段C1q、C3a和C5a。结果表明,GM-CSF活性中心衍生的合成肽(Acegram-spray)局部应用于粘膜可显著影响中性粒细胞的功能性杀菌活性(nbt活性),增加T辅助细胞的百分比,并升高C3a补体片段。这些发现表明,合成肽主要影响先天免疫因子。然而,在其他免疫系统参数中没有观察到显著差异。因此,开发针对免疫系统受损的covid后患者的治疗方法可能需要寻找针对T、B和NK细胞的额外免疫调节剂。各种免疫调节剂对新冠肺炎后患者免疫系统的影响有待进一步研究。
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引用次数: 0
<i>In vitro</i> immunomodulatory effect of siRNA complexes in the influenza infection & lt; i&gt vitro&lt; / i&gt;siRNA复合物在流感感染中的免疫调节作用
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13984-ivi
Evgeny A. Pashkov, R. V. Samoilikov, G. A. Pryanikov, A. S. Bykov, E. P. Pashkov, A. V. Poddubikov, O. A. Svitich, V. V. Zverev
About 1.2 billion cases of influenza infection with up to 5 million cases of severe disease and up to 650,000 deaths from influenza and its complications are registered annually worldwide. High rates of morbidity and mortality are attributed to immunomodulatory properties of some proteins produced by the influenza viruses. Among these proteins, NS-1 is the most studied. One of its main functions is to disrupt the functioning of interferon-mediated defense mechanisms of the body thus causing suppressed production of different components of humoral immunity, which leads to an insufficiency of the immune response. It is known that miRNAs directed to cellular genes, which are involved in the process of viral reproduction, showing a pronounced antiviral activity. At the same time, only few studies have been focused on evaluation of their immunotropic effects. Therefore, the aim of our study was to quantify the concentrations of IFN, IFN, TNF and IL-10 cytokines as a result of complex suppression of the cellular FLT4, Nup98 and Nup205 gene activity, whose expression products play an important role in the reproduction of the influenza virus. We have shown that the use of siRNA complexes also leads to an increase in the IFN, IFN, TNF and IL-10 concentrations. IL-10 production is absent on the first day after infection, but begins to increase on the second and third days. Moreover, in some cases, there is an increase in IFN and IFN concentration on the first day after infection followed by decrease in their concentrations by the third day. This finding indicates that, upon supplement of the siRNA complexes, the cytokine profile is normalized under the influence of IL-10.
全世界每年登记的流感感染病例约为12亿例,其中多达500万例严重疾病和多达65万人死于流感及其并发症。高发病率和高死亡率归因于流感病毒产生的某些蛋白质的免疫调节特性。在这些蛋白中,NS-1是研究最多的。其主要功能之一是破坏干扰素介导的机体防御机制的功能,从而抑制体液免疫不同成分的产生,从而导致免疫应答不足。众所周知,mirna指向参与病毒繁殖过程的细胞基因,显示出明显的抗病毒活性。同时,对其免疫效应的评价研究较少。因此,我们的研究目的是量化IFN、IFN、TNF和IL-10细胞因子的浓度,这是复杂抑制细胞FLT4、Nup98和Nup205基因活性的结果,这些基因的表达产物在流感病毒的繁殖中起重要作用。 我们已经证明,siRNA复合物的使用也会导致IFN、IFN、TNF和IL-10浓度的增加。IL-10在感染后第一天不产生,但在第2天和第3天开始增加。此外,在某些情况下,感染后第一天IFN和IFN浓度升高,然后在第三天浓度下降。这一发现表明,在补充siRNA复合物后,细胞因子谱在IL-10的影响下正常化。
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引用次数: 0
期刊
Russian journal of immunology : RJI : official journal of Russian Society of Immunology
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