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Role of cytokines, neuropeptids and matrix metalloproteinases in the immunopathogenesis of retinal neurodegeneration in diabetic retinopathy 细胞因子、神经肽和基质金属蛋白酶在糖尿病视网膜病变视网膜神经变性免疫发病机制中的作用
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1157-roc
M. P. Ruchkin, E. Markelova, G. A. Fedyashev, V. N. Yuschyuk
Currently, diabetic retinopathy (DR) is considered both a vascular lesion, as well as a neurodegenerative disease. The normal functioning of the glia and retinal neurons depends on the balance between the cytokine system, neurotrophic factors and matrix metalloproteinases. The disorders that occur in these systems are assigned an important role in many neurodegenerative processes. The purpose of the present study was to determine the levels of IL-1, IL-17A, TNF, IFN, IL-10, TGF-1, TGF-2, TGF-3, MMP- 2, MMP-7, MMP-9, TIMP-1, TIMP-2, S100b protein, BDNF and NGF in the serum of patients with type 2 diabetes mellitus with signs of retinal neurodegeneration, and to identify additional immunological markers for diagnosis and prediction of their clinical course. The study included 80 patients with endocrinogically verified diagnosis of type 2 diabetes. All subjects were examined at an optical coherent tomograph RTVue-100 (USA), and the volume of focal loss of retinal ganglion cells (FLV) was determined. According to its results, the patients of the main group were divided into 2 subgroups. The first group included 22 persons in whom the FLV indexes did not show significant differences from the controls. The second group included 58 patients with a significantly larger FLV volume. In the subgroup of patients with high level of focal GCS loss, a significant increase in the level of IL-1 and IL-10 deficiency was revealed in comparison with the controls, and the subgroup without significant losses of GCS over the entire observation period. TGF-3 deficiency was found in patients of subgroup 2 versus controls and subgroup 1. An imbalance in the tissue proteolysis system was revealed, MMP-9 and TIMP-2 levels were elevated, and MMP-7 levels were decreased in both subgroups compared to controls. When analyzing serum contents of neurospecific proteins in the group of patients with OCT signs of retinal neurodegeneration, high levels of the S100b protein and NGF were revealed, in contrast to the control group and subgroup 1.
目前,糖尿病视网膜病变(DR)被认为既是一种血管病变,也是一种神经退行性疾病。神经胶质和视网膜神经元的正常功能依赖于细胞因子系统、神经营养因子和基质金属蛋白酶之间的平衡。在这些系统中发生的疾病在许多神经退行性过程中起着重要作用。本研究的目的是检测伴有视网膜神经退行性变体征的2型糖尿病患者血清中IL-1、IL-17A、TNF、IFN、IL-10、TGF-1、TGF-2、TGF-3、MMP- 2、MMP-7、MMP-9、TIMP-1、TIMP-2、S100b蛋白、BDNF和NGF的水平,并寻找用于诊断和预测其临床病程的其他免疫学标志物。该研究包括80名经内分泌学证实诊断为2型糖尿病的患者。所有受试者在RTVue-100(美国)光学相干断层扫描仪上进行检查,并测定视网膜神经节细胞(FLV)的局灶性损失体积。根据结果将主组患者分为2个亚组。第一组包括22人,其中FLV指数与对照组没有显着差异。第二组包括58例FLV容量明显较大的患者。在局灶性GCS高水平丢失患者亚组中,与对照组相比,IL-1和IL-10缺乏症水平显著升高,而在整个观察期内,GCS无明显丢失亚组。与对照组和亚组1相比,在亚组2患者中发现TGF-3缺乏。组织蛋白水解系统失衡,与对照组相比,两个亚组的MMP-9和TIMP-2水平升高,MMP-7水平降低。在分析视网膜神经退行性变OCT体征患者血清中神经特异性蛋白的含量时,与对照组和亚组1相比,S100b蛋白和NGF水平较高。
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引用次数: 0
Population immunity in residents of the Kaliningrad region to current antigenic variants of influenza viruses over 2018-2021 2018-2021年加里宁格勒地区居民对当前流感病毒抗原变异的人口免疫力
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1170-pii
A. Goncharov, O. A. Egorenkova, V. Shupletsova
The article presents the results of population immunity assessment in residents of the Kaliningrad region to current antigenic variants of influenza viruses over the period of 2018 to 2021. To assess spectrum of influenza types circulating in Kaliningrad region, the real-time PCR method was used using AmpliSense reagent kits. The biological material for the study was obtained from oropharyngeal swabs from the persons who applied to polyclinics with inflammatory diseases of upper respiratory tract, or underwent treatment at the out- or inpatient basis in a healthcare facilities of Kaliningrad region. Humoral immunity was assessed by testing blood sera obtained from healthy residents of Kaliningrad region during periodic prophylactic examinations at the city and regional polyclinics. The study of residents covered all age groups. For the period of 2018-2021, more than 14,000 studies have been carried out. Determination of specific serum antibody titers was carried out by staging the hemagglutination suppression reaction using local influenza antigens (LLC PPDP, St. Petersburg). Antibody titers of 1/40 and higher were considered sufficient to reduce the risk of disease by 50%. During the study period, 2165 cases of influenza were confirmed in the region by laboratory tests. Over the study period, the A(H1N1) pdm serotype proved to be the major strain causing influenza, its proportion reached 57.5%. However, along with A(H1N1) pdm, a significant contribution was also made the A(H3N2) strain to the epidemic process, being the etiological cause of influenza infection in 2019 (42.2%), type B influenza strains being actual in 2020 (42.5%). Over the period of 2018-2021, 420 samples of blood sera from vaccinated and non-vaccinated individuals were tested for specific antibodies. The sera were taken 1-2 months after vaccination and between epidemic rises of influenza (April-May). In vaccinated individuals, the antibody titer was protective in 58.3-64.5%. In this group of persons, the titer sufficient to produce immunity was maintained over the spring/summer period. Among those persons who refused vaccination, a protective antibody titer in the pre-epidemic period was noted in 41.2% of the examined, and during the off-season it was detected in 37.4% of the volunteers. Thus, the A(H1N1) pdm strain was the main etiological factor of influenza in Kaliningrad Region in 2018-2021. The protective level of antibodies in vaccinated population over the period preceding the epidemic peak, was observed 30% more often than in unvaccinated individuals. High incidence of influenza B strains noted in 2020 appears to require a change of specific vaccine preparation.
本文介绍了2018年至2021年期间加里宁格勒地区居民对当前流感病毒抗原变异的人群免疫评估结果。为了评估加里宁格勒地区流行的流感类型谱,采用实时荧光定量PCR方法,使用AmpliSense试剂盒。该研究的生物材料是从加里宁格勒地区医疗机构门诊或住院治疗的上呼吸道炎症性疾病患者的口咽拭子中获得的。体液免疫是通过检测加里宁格勒地区健康居民在城市和地区综合诊所定期预防性检查期间采集的血清来评估的。对居民的研究涵盖了所有年龄组。在2018年至2021年期间,开展了14000多项研究。采用当地流感抗原(LLC PPDP, St. Petersburg)分期进行血凝抑制反应,测定特异性血清抗体滴度。抗体滴度为1/40或更高被认为足以降低50%的疾病风险。在研究期间,该区域通过实验室检测确认了2165例流感病例。在研究期间,A(H1N1) pdm血清型被证明是引起流感的主要菌株,其比例达到57.5%。然而,除了甲型H1N1流感,甲型H3N2流感毒株对流感流行过程也有重要贡献,是2019年流感感染的病因(42.2%),乙型流感毒株是2020年的实际病因(42.5%)。在2018-2021年期间,对接种疫苗和未接种疫苗的人的420份血清样本进行了特异性抗体检测。在接种疫苗后1-2个月和流感流行上升期间(4 - 5月)采集血清。在接种者中,抗体效价为58.3-64.5%。在这组人中,在春夏期间维持了足以产生免疫力的滴度。在拒绝接种疫苗的人群中,41.2%的被检查者在流行前检测到保护性抗体滴度,37.4%的被检查者在淡季检测到保护性抗体滴度。因此,甲型H1N1 pdm毒株是2018-2021年加里宁格勒地区流感的主要病原。在流行高峰之前的一段时间内,接种疫苗的人群中抗体的保护水平比未接种疫苗的人群高30%。注意到2020年乙型流感毒株的高发病率似乎需要改变特定的疫苗制备。
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引用次数: 0
Cytokines of the IL-6 family, adiponectin and leptin levels in patients with metabolic syndrome during the post-COVID period 新冠肺炎后代谢综合征患者IL-6家族细胞因子、脂联素和瘦素水平的变化
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1174-cot
O. Radaeva, A. Simbirtsev, Y. Kostina, E. Negodnova, D. D. Besheynov, S. V. Mashnina, V. Eremeev
COVID-19 is a multisystem disease, but the extent of its consequences is currently poorly understood, especially in the persons with metabolic disorders. The aim of the present study was to evaluate the special changes in the cytokines of IL-6 family (IL-6 and sIL-6, LIF and sLIFr), adiponectin and leptin within 360 days after SARS-CoV-2 infection in the patients with metabolic syndrome (MetS), to discern features of immunopathogenesis depending on previous vaccination against COVID-19. We have classified the patients in two groups: (1) patients with MetS who underwent COVID-19 6-12 months after full-course vaccination with a vector vaccine (n = 32); (2) patients with MetS who underwent COVID-19 without story of vaccination (n = 29). Control group included conditionally healthy individuals without MetS: (3) vaccinated, and (4) non-vaccinated, who also had COVID-19. The levels of IL-6 and sIL-6, LIF and sLIFr, leptin and adiponectin, NO, ADMA, SDMA were determined by ELISA technique. In patients with MetS, changes in cytokine regulation towards proinflammatory reactions were revealed (an increase in blood IL-6 and leptin levels), which was most pronounced in MetS within first 30 days post-COVID, but with a number of changes which remained for 12 months (e.g., increased leptin concentration in blood). Vaccination against COVID-19 reduced the severity of pro-inflammatory changes in the sIL- 6r/ IL-6 and leptin/adiponectin systems towards protective adiponectin. However, the persistent increase in leptin was not canceled. When interpreting these results, no negative differences were revealed in the group of once vaccinated individuals with MetS, concerning the mentioned cytokine regulations of MetS over 1 year after COVID-19. The univariate, and then multifactorial correlation analysis between serum contents of sIL- 6r/ IL- 6, LIF/ sLIFr, adiponectin and leptin and the levels of vasoactive substances (NO, ADMA and SDMA), glycated hemoglobin, LDL has shown that the increased ratio of sIL-6r/IL-6 is an independent factor for the NO reduction of (r = 0.74, p 0.01); an increase in sLIFr positively correlates with increase in glycated hemoglobin (r = 0.69, p 0.01), and an association with increase of ADMA (r = 0.82, p 0.001), leptin (in this model) are shown to be an independent factor of LDL increase (r = 0.69, p 0.05). Influence of pre-COVID modifiable factors, in particular, vaccination, is relevant in terms of reducing the likelihood of progression of pre-existing chronic diseases (hypertension, atherosclerosis, diabetes mellitus) in the persons with MetS after COVID-19 and has prospects for implementation into clinical practice.
COVID-19是一种多系统疾病,但目前对其后果的程度知之甚少,特别是对代谢紊乱患者。本研究旨在评价代谢综合征(MetS)患者感染SARS-CoV-2后360天内IL-6家族细胞因子(IL-6和sIL-6、LIF和sLIFr)、脂联素和瘦素的特殊变化,以了解与既往接种COVID-19相关的免疫发病特征。我们将患者分为两组:(1)在全程接种载体疫苗后6-12个月感染COVID-19的MetS患者(n = 32);(2)接受COVID-19治疗但未接种疫苗的MetS患者(n = 29)。对照组包括没有MetS的条件健康个体:(3)接种疫苗,(4)未接种疫苗,同时患有COVID-19。ELISA法检测各组血清IL-6、sIL-6、LIF、sLIFr、瘦素、脂联素、NO、ADMA、SDMA水平。在MetS患者中,细胞因子对促炎反应的调节发生了变化(血液IL-6和瘦素水平升高),这在MetS患者中在covid后的前30天内最为明显,但在12个月内仍有一些变化(例如血液中瘦素浓度升高)。针对COVID-19的疫苗接种降低了sIL- 6r/ IL-6和瘦素/脂联素系统对保护性脂联素的促炎变化的严重程度。然而,瘦素的持续增加并没有被取消。在解释这些结果时,在接种过MetS的人群中,关于上述细胞因子在COVID-19后1年内对MetS的调节,没有发现负性差异。血清sIL-6r/IL-6、LIF/ sLIFr、脂联素和瘦素含量与血管活性物质(NO、ADMA和SDMA)、糖化血红蛋白、LDL水平的单因素及多因素相关分析表明,sIL-6r/IL-6比值升高是NO降低的独立因素(r = 0.74, p 0.01);sLIFr的增加与糖化血红蛋白的增加呈正相关(r = 0.69, p 0.01),与ADMA的增加相关(r = 0.82, p 0.001),瘦素(在该模型中)被证明是LDL增加的独立因素(r = 0.69, p 0.05)。COVID-19前可改变因素的影响,特别是疫苗接种,在降低COVID-19后MetS患者原有慢性疾病(高血压、动脉粥样硬化、糖尿病)进展的可能性方面具有相关性,并且具有应用于临床实践的前景。
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引用次数: 0
Experimental in vitro phenotype reprogramming of two subsets of neutrophilic granulocytes in children with acute destructive pneumonia by means of a synthetic hexapeptide 利用合成六肽对急性破坏性肺炎患儿中性粒细胞两个亚群的实验性体外表型重编程
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1175-eiv
I. Nesterova, V. N. Chapurina, G. Chudilova, V. Tarakanov
Effector dysfunctions of neutrophil granulocytes are often associated with the occurrence of dysregulatory processes in the antibacterial immune defense. Acute destructive pneumonia is a severe purulent-inflammatory disease associated with discordant functions of effector mechanisms of neutrophil granulocytes and emergence of negatively transformed cell subsets. Therefore, the search for new experimental approaches aimed at re-orientation of negatively altered phenotype of distinct subsets of neutrophilic granulocytes in the children with acute destructive pneumonia by means of various immunotropic substances is quite relevant. The aim of the study was to evaluate the modulating effects of synthetic hexapeptide (Arginyl-alpha-Aspartyl-Lysyl-Valyl-Tyrosyl-Arginine) on the contents and phenotype of 2 functionally significant subsets of major (CD16+CD64-CD32+CD11b+) and minor (CD16+CD64+CD32+CD11b+) subpopulations of neutrophils in a closed in vitro experimental system sampled in the children with atypical acute destructive pneumonia. We have examined twenty peripheral blood samples from 10 children with acute destructive pneumonia, and 40 blood samples of 20 healthy children 2-4 years old. Immunophenotyping of neutrophil granulocytes classified in 2 subsets was performed on the basis of expression density of membrane receptors, according to MFI criteria. Phenotypic features of neutrophil granulocyte subsets were evaluated in the in vitro system before and after incubation of peripheral blood with Hexapeptide (10-6 g/L; 37 C, 60 min). In children with acute destructive pneumonia, compared with conditionally healthy children, the following variants of negative transformation of the neutrophil subsets were established: a significant decrease in the ratios of the major subset, i.e., from 98.0 (96.9-98.7) % o 55.8 (35.3-74.8) %, with a decreased CD16 and CD11b density expression according to MFI, and a significantly increase ratio of the minor neutrophil subset: from 1.3 (0.4-1.6) % to 52.6 (41.8-54.9) %, with increased expression of CD11b receptor, and a decrease in CD64 expression. Immunomodulatory effects of Hexapeptide upon neutrophil granulocytes of children with acute destructive pneumonia have been demonstrated in the closed in vitro system showing positive phenotype remodeling of both cell subsets in the absence of significant quantitative changes. Thus, upon treatment with the hexapeptide, we have found a significantly increased expression of activation receptors CD16, CD11b in the major subset, and a significant decrease in their expression for the minor subset to the levels typical to healthy children. At the same time, hexapeptide did not affect the studied subsets of neutrophils from healthy children, except of increased CD64 expression in the minor subset. The obtained data can be used in future to develop new approaches to the targeted immunotherapy aimed at correcting the phenotype of neutrophil granulocyte subsets in acute destructive p
中性粒细胞的效应功能障碍通常与抗菌免疫防御中失调过程的发生有关。急性破坏性肺炎是一种严重的脓性炎症性疾病,与中性粒细胞效应机制的功能失调和负转化细胞亚群的出现有关。因此,寻找新的实验方法,旨在通过各种免疫物质重新定位急性破坏性肺炎儿童中性粒细胞不同亚群的负性表型改变是非常重要的。本研究的目的是评估人工合成六肽(精氨酸- α -天冬氨酸-赖氨酸-缬氨酸-酪氨酸-精氨酸)对非典型急性破坏性肺炎患儿中性粒细胞主要亚群(CD16+CD64-CD32+CD11b+)和次要亚群(CD16+CD64+CD32+CD11b+)的含量和表型的调节作用。我们检测了10例急性破坏性肺炎患儿的20份外周血样本和20例2-4岁健康儿童的40份血液样本。根据膜受体的表达密度,按照MFI标准,将中性粒细胞分为2个亚群进行免疫分型。用Hexapeptide (10-6 g/L;37℃,60分钟)。在急性破坏性肺炎患儿中,与有条件健康儿童相比,中性粒细胞亚群的阴性转化存在以下变异:主要亚群的比例显著下降,即从98.0%(96.9-98.7)%降至55.8% (35.3-74.8)%,MFI显示CD16和CD11b密度表达降低,次要中性粒细胞亚群的比例显著增加。从1.3(0.4-1.6)%增加到52.6 (41.8-54.9)%,CD11b受体表达增加,CD64表达减少。六肽对急性破坏性肺炎儿童中性粒细胞的免疫调节作用已在封闭的体外系统中得到证实,在没有显著定量变化的情况下,两种细胞亚群的表型重塑均呈阳性。因此,在用六肽治疗后,我们发现激活受体CD16、CD11b在主要亚群中的表达显著增加,而在次要亚群中的表达显著降低至健康儿童的典型水平。同时,六肽不影响健康儿童中性粒细胞亚群的研究,除了在小亚群中CD64表达增加。获得的数据可用于未来开发靶向免疫治疗的新方法,旨在纠正儿童急性破坏性肺炎中性粒细胞亚群的表型。
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引用次数: 0
Prognosis of COVID-19 outcomes and risk prediction for the development of post-COVID syndrome COVID-19结局的预后及发生后综合征的风险预测
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1199-poc
M. G. Atazhakhova, G. Chudilova, I. Nesterova
At the present time, the new laboratory diagnostic markers are required which may predict complications over the post-COVID period, as well as improve diagnostics of post-COVID syndrome in the patients who underwent COVID-19. Despite the fact that changes in respiratory system are the most common manifestations of COVID-19, extrapulmonary manifestations followed by the wide range of persistent symptoms and/or delayed complications may lead to multiple organ lesions of varying severity: from symptomless to fatal forms. A number of symptoms in the developed post-COVID syndrome may persist for 3 weeks, or to be prolonged up to 6 months and later. The purpose of the study was to investigate the informativity of an early integrative diagnostic index developed by us, enabling prediction of the COVID-19 outcome, and potential development of early post-COVID syndrome. Peripheral blood samples were examined in 60 patients (38-82 years old) diagnosed with COVID-19 of moderate severity (CT-2.3) during their inpatient treatment; 30 patients (38-62 years old) in the early post-COVID period and 34 patients (38-65 years old) with early post-COVID syndrome. The comparison group consisted of 100 healthy sex- and age-matched volunteers. The IDP, an integrative diagnostic index, was calculated as a marker including the ratio of the relative neutrophil-to-lymphocyte numbers, as well as the levels of C-reactive protein (CRP), by the following formule: IDP = (% neutrophilic granulocytes CRP) / % lymphocytes. We have found that, during the inpatient treatment, upon acute clinical manifestations, IDP in study group 1 was increased 12.5 times against the comparison group. It should be noted that all patients were discharged from the hospital in compliance with official criteria, according to Temporary Guidelines. In the study group 2, during early postcovid period, IDP remained 3.4-fold elevated against the comparison group. According to the chest CT data, the patients had signs of a fibrous component, organizing stage of pneumonia and consolidation foci in the lung tissue. Among the group 3 patients (early post-COVID syndrome), IDP was increased three-fold against the comparison group, accompanied by the documented signs of chronic fatigue syndrome and cognitive impairment. The IDP can be used as a marker for the prognosis of clinical outcome and a predictor of the evolving complications during the early post-COVID period and upon development of early post-COVID syndrome in the patients who have undergone COVID-19.
目前,需要新的实验室诊断标志物来预测COVID-19后的并发症,并提高对COVID-19患者后综合征的诊断。尽管呼吸系统的变化是COVID-19最常见的表现,但肺外表现随后出现广泛的持续症状和/或延迟并发症,可能导致不同严重程度的多器官病变:从无症状到致命形式。出现后冠状病毒综合征的一些症状可能持续3周,或延长至6个月或更长时间。该研究的目的是研究由我们开发的早期综合诊断指数的信息性,该指数能够预测COVID-19的结局,以及早期后covid综合征的潜在发展。对60例(38 ~ 82岁)诊断为COVID-19中度严重程度(CT-2.3)的患者在住院治疗期间进行外周血检测;术后早期30例(38 ~ 62岁),早期34例(38 ~ 65岁)。对照组由100名性别和年龄相匹配的健康志愿者组成。IDP是一种综合诊断指数,作为一种标志物,包括中性粒细胞与淋巴细胞的相对数量之比,以及c反应蛋白(CRP)水平,计算公式如下:IDP =(中性粒细胞CRP %) /淋巴细胞%。我们发现,在住院治疗期间,一旦出现急性临床表现,研究1组的IDP比对照组增加了12.5倍。应当指出的是,根据《临时准则》,所有患者均按照官方标准出院。在研究组2中,在covid后早期,IDP仍比对照组高3.4倍。胸部CT资料显示,患者有纤维成分、肺炎组织期及肺组织实变灶征象。在第3组患者(早期后冠状病毒综合征)中,IDP比对照组增加了3倍,并伴有慢性疲劳综合征和认知障碍的记录迹象。IDP可作为临床预后的标志,并可作为COVID-19后早期并发症发展的预测指标,以及COVID-19后早期综合征的发展。
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引用次数: 0
Evaluation of anti-TNF treatment efficiency in children with immune-dependent diseases by means of testing the NF-κB activity in lymphocyte populations 通过检测淋巴细胞群中NF-κB活性评价儿童免疫依赖性疾病抗tnf治疗效果
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1191-eoa
S. Petrichuk, T. Radygina, D. Kuptsova, O. Kurbatova, E. Semikina, N. Murashkin, A. Potapov, A. Fisenko
Nuclear transcription factor B (NF-B) regulates innate and adaptive immunity functions and mediates inflammatory responses by activating proinflammatory cytokine gene transcription. TNF inhibitors block the NF-B signaling pathway, thus reducing inflammatory activity. The aim of the study was to evaluate the informativity of NF-kB transcription factor determination in the lymphocyte populations in children with inflammatory bowel disease (IBD) and psoriasis to assess the efficacy of anti-TNF therapy. We have examined 124 children with IBD and 55 children with psoriasis vulgaris administered maintenance anti-TNF therapy, and 30 healthy children. Stratification into the study groups was carried out according to PCDIA, PUCAI, PASI indices ( 10, remission). The number of cells with NF-B translocation was determined by flow cytometry with vusualization (Amnis ImageStreamX Mk II). Statistical evaluation was performed using Statistica 10.0 and SPSS 16.0. The highest number of cells with NF-B translocation was detected in B-lymphocytes and NK cells, thus being significantly higher than in T helper cells and cytotoxic T lymphocytes (p = 0.000). The percentage of cells with translocation of NF-B in populations of NK cells, T helper, cytotoxic T lymphocytes, Th17 lymphocytes, cytotoxic Th17 lymphocytes (Tc17) and Treg was increased in the patients at the acute disease stage against the comparison group. In the remission state, NF-B activity in lymphocyte populations was lower than in acute stage. In remission of psoriasis, NF-B activity in B lymphocytes, NK cells, and cytotoxic T lymphocytes was significantly lower than in comparison group. In IBD remission state, the NF-B activity was elevated only in T-helper cells. The level of NF-B translocation in the NK-cell population differed in children with IBD and psoriasis, both in acute phase (IBD, 46.2% (34-58); psoriasis, 36.5% (29-48), p = 0.041), and remission of disease (IBD, 25.4% (22-35); psoriasis, 19.1% (17-22), p = 0.000). ROC analysis of the data from exacerbation/remission states assessed as the NK cell numbers with NF-B translocation showed a good quality of the stratification model (AUC 0.8): The cut-off value in IBD was 41% (Se = 65.4; Sp = 89.1), and in psoriasis it was 23% (Se = 85.2; Sp = 94.7). The informativity of NF-B translocation level in lymphocyte populations in children with IBD and psoriasis was shown to correlate with efficacy of anti-TNF therapy. Exacerbation the disease with decreased therapeutic response is characterized by NF-B activation in lymphocyte populations in the children with IBD and psoriasis.
核转录因子B (NF-B)通过激活促炎细胞因子基因转录,调节先天免疫和适应性免疫功能,介导炎症反应。TNF抑制剂阻断NF-B信号通路,从而降低炎症活性。该研究的目的是评估NF-kB转录因子测定在炎症性肠病(IBD)和牛皮癣儿童淋巴细胞群中的信息性,以评估抗tnf治疗的疗效。我们对124名IBD患儿和55名寻常型牛皮癣患儿进行了维持抗tnf治疗,并对30名健康儿童进行了检查。根据PCDIA、PUCAI、PASI指数(10,缓解)进行分组。流式细胞术(Amnis ImageStreamX Mk II)检测NF-B易位细胞数。统计学评价采用Statistica 10.0和SPSS 16.0进行。发生NF-B易位的细胞以b淋巴细胞和NK细胞最多,显著高于T辅助细胞和细胞毒性T淋巴细胞(p = 0.000)。急性期患者NK细胞、辅助T细胞、细胞毒性T淋巴细胞、Th17淋巴细胞、细胞毒性Th17淋巴细胞(Tc17)和Treg细胞中NF-B易位细胞的比例较对照组升高。缓解期淋巴细胞群NF-B活性低于急性期。银屑病缓解后,B淋巴细胞、NK细胞和细胞毒性T淋巴细胞的NF-B活性明显低于对照组。在IBD缓解状态下,NF-B活性仅在t辅助细胞中升高。IBD和牛皮癣患儿nk细胞群中NF-B易位水平不同,均在急性期(IBD, 46.2% (34-58);牛皮癣,36.5% (29-48),p = 0.041),疾病缓解(IBD, 25.4% (22-35);银屑病,19.1% (17-22),p = 0.000)。以NF-B易位的NK细胞数量评估加重/缓解状态数据的ROC分析显示,分层模型质量良好(AUC为0.8):IBD的临界值为41% (Se = 65.4;Sp = 89.1),牛皮癣为23% (Se = 85.2;Sp = 94.7)。IBD和牛皮癣患儿淋巴细胞群中NF-B易位水平的信息性与抗tnf治疗的疗效相关。炎症性肠病和牛皮癣患儿的淋巴细胞群NF-B活化是疾病恶化和治疗反应降低的特征。
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引用次数: 0
Changes in mononuclear cell subsets in capillary and venous blood of patients with psoriasis depending on the treatment 银屑病患者毛细血管和静脉血中单核细胞亚群随治疗的变化
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1159-cim
S. V. Sennikova, A. Toptygina
Topical glucocorticoids are conventionally used to treat psoriasis, but such treatment provides a short-term effect, and may cause various complications during long-term usage. A detailed study of the immunopathogenesis of psoriasis has made it possible to use bioengineered drugs that block the main cytokines. It has been shown that IL-36 plays an important regulatory role in pathogenesis of psoriasis. The aim of the study was to study therapeutic effect of patients with psoriasis using topical glucocorticoid hormone versus IL- 36 receptor antagonist (RAIL-36), with respect to clinical course of psoriasis and the subsets of mononuclear cells in venous and capillary blood taken close to the focus of inflammation. 16 patients with psoriasis (group 1a) received 0.1% mometasone cream for 14 days; 20 patients of group 1b received a gel containing 0.4% recombinant RAIL-36 for 14 days. Control group included 20 healthy adults. Treatment efficacy was assessed by PASI, DISHS and DLQI indices. 19 lymphocyte subsets and 3 monocyte subsets were assessed by four-color staining of whole capillary and venous blood with erythrocyte lysis using BD Biosciences (USA) technologies and reagents. It was shown that both drugs led to a decrease in the severity of the disease at the end of treatment. However, 2 weeks after the end of treatment in group 1a, the disease indexes nearly returned to the initial values. Meanwhile, the reduced index levels persisted 2 weeks later in group 1b. Significant deviations (more pronounced in capillary blood) were revealed for the levels of several leukocyte subsets in the psoriasis patients compared with healthy persons. As a result of treatment, we have revealed some changes in the levels of leukocyte subsets common to the two groups, and special differences for the two treatment options, that were more pronounced in capillary blood samples. Both medical preparations used are suitable for treatment of psoriasis.
局部糖皮质激素通常用于治疗牛皮癣,但这种治疗提供短期效果,并可能在长期使用中引起各种并发症。对银屑病免疫发病机制的详细研究使得使用阻断主要细胞因子的生物工程药物成为可能。研究表明,IL-36在银屑病的发病过程中起着重要的调节作用。本研究的目的是研究外用糖皮质激素与IL-36受体拮抗剂(RAIL-36)对银屑病患者的治疗效果,以及银屑病的临床病程和炎症病灶附近静脉和毛细血管血中单个核细胞亚群的变化。16例银屑病患者(1a组)接受0.1%莫米松乳膏治疗,疗程14 d;1b组20例患者接受含有0.4%重组RAIL-36的凝胶治疗,持续14天。对照组为健康成人20例。采用PASI、dish、DLQI指标评价治疗效果。采用美国BD Biosciences公司的技术和试剂,采用红细胞溶解法对全毛细血管和静脉血进行四色染色,测定19个淋巴细胞亚群和3个单核细胞亚群。研究表明,这两种药物在治疗结束时都能降低疾病的严重程度。然而,在1a组治疗结束2周后,疾病指标几乎恢复到初始值。与此同时,1b组的指数下降水平在2周后持续存在。与健康人相比,银屑病患者的几种白细胞亚群水平存在显著差异(在毛细血管血液中更为明显)。作为治疗的结果,我们揭示了两组共同的白细胞亚群水平的一些变化,以及两种治疗方案的特殊差异,这在毛细血管血液样本中更为明显。所使用的两种药物制剂均适用于治疗牛皮癣。
{"title":"Changes in mononuclear cell subsets in capillary and venous blood of patients with psoriasis depending on the treatment","authors":"S. V. Sennikova, A. Toptygina","doi":"10.46235/1028-7221-1159-cim","DOIUrl":"https://doi.org/10.46235/1028-7221-1159-cim","url":null,"abstract":"Topical glucocorticoids are conventionally used to treat psoriasis, but such treatment provides a short-term effect, and may cause various complications during long-term usage. A detailed study of the immunopathogenesis of psoriasis has made it possible to use bioengineered drugs that block the main cytokines. It has been shown that IL-36 plays an important regulatory role in pathogenesis of psoriasis. The aim of the study was to study therapeutic effect of patients with psoriasis using topical glucocorticoid hormone versus IL- 36 receptor antagonist (RAIL-36), with respect to clinical course of psoriasis and the subsets of mononuclear cells in venous and capillary blood taken close to the focus of inflammation. 16 patients with psoriasis (group 1a) received 0.1% mometasone cream for 14 days; 20 patients of group 1b received a gel containing 0.4% recombinant RAIL-36 for 14 days. Control group included 20 healthy adults. Treatment efficacy was assessed by PASI, DISHS and DLQI indices. 19 lymphocyte subsets and 3 monocyte subsets were assessed by four-color staining of whole capillary and venous blood with erythrocyte lysis using BD Biosciences (USA) technologies and reagents. It was shown that both drugs led to a decrease in the severity of the disease at the end of treatment. However, 2 weeks after the end of treatment in group 1a, the disease indexes nearly returned to the initial values. Meanwhile, the reduced index levels persisted 2 weeks later in group 1b. Significant deviations (more pronounced in capillary blood) were revealed for the levels of several leukocyte subsets in the psoriasis patients compared with healthy persons. As a result of treatment, we have revealed some changes in the levels of leukocyte subsets common to the two groups, and special differences for the two treatment options, that were more pronounced in capillary blood samples. Both medical preparations used are suitable for treatment of psoriasis.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89472625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Local immune state in the women with miscarriage 流产妇女的局部免疫状态
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1200-lis
O. Abramovskikh, Y. Loginova
Functional state of immunity provides maintenance of immunological tolerance for allogeneic fetus, and high level of local protection against antigenic stimulation. Increased functional activity of phagocytic cells at systemic and local levels may cause impairment of complete fetoplacental complex, thus leading to abortion. The purpose of our study was to assess the state of local immunity in women with pregnancy loss. The study involved 174 women in their reproductive age. The first group consisted of 65 patients (37.4%) with a diagnosis of miscarriage, the history of 2 abortions over the period from conception to the 20th week of gestation. The second group included 37 patients (21.2%) with documented recurrent pregnancy loss, with a history of 3 miscarriages. The control group consisted of 72 conditionally healthy women (41.4%) who had 2 or more term pregnancies with the same partner, without a history of obstetric and gynecological complications. Their mean age was 366 years old. Total number and viability of leukocytes, the indices of functional neutrophil activity, their functional reserve and neutrophil stimulation index were determined in cervical mucosal samples over the first phase of the menstrual cycle. In the first phase of menstrual cycle, the women with miscarriage and recurrent pregnancy loss exhibited a statistically significant increase of phagocytosis by the neutrophils from cervical mucus as compared to the group of conditionally healthy women. Intensity of neutrophil phagocytosis in cervical mucus reached higher values in the women with recurrent pregnancy loss more often, compared to the control group. Evaluation of the functional reserve of cervical mucus neutrophils in the subjects with recurrent pregnancy loss and miscarriage showed a trend towards statistically significant differences: this parameter was higher in the patients than in control group. The ability of cervical mucosal neutrophils to produce reactive oxygen species (both spontaneous and induced) did not show statistically significant differences between the patients and controls. Hence, we have observed aberrant functional activity of neutrophilic granulocytes from cervical mucosa in the groups of women with 2 or more abortions, without changing ability of the cells to produce reactive oxygen species. This finding may be explained by prevalence of oxygen-independent mechanisms of intracellular killing, thus suggesting a role of neutrophils for impaired balance of immunological tolerance in pregnant women at the local level.
免疫功能状态维持异体胎儿的免疫耐受,并对抗原刺激提供高水平的局部保护。吞噬细胞在全身和局部水平的功能活性增加可能导致完整胎胎盘复合体的损害,从而导致流产。本研究的目的是评估流产妇女的局部免疫状态。这项研究涉及174名育龄妇女。第一组为65例(37.4%),诊断为流产,从受孕到妊娠20周有2次流产史。第二组包括37例(21.2%)复发性流产,有3次流产史。对照组包括72名有条件的健康妇女(41.4%),她们与同一伴侣有2次或2次以上足月妊娠,无产科和妇科并发症史。平均年龄为366岁。测定月经第一阶段宫颈黏膜标本白细胞总数、活力、功能性中性粒细胞活性指数、功能储备和中性粒细胞刺激指数。在月经周期的第一阶段,流产和反复流产的妇女与条件健康的妇女相比,宫颈粘液中嗜中性粒细胞的吞噬能力有统计学上的显著增加。与对照组相比,宫颈粘液中性粒细胞吞噬强度在反复流产的妇女中达到更高的值。宫颈粘液中性粒细胞功能储备在反复流产和流产组中有统计学差异的趋势,患者的该参数高于对照组。宫颈粘膜中性粒细胞产生活性氧(自发的和诱导的)的能力在患者和对照组之间没有统计学上的显著差异。因此,我们观察到2次或2次以上流产的妇女宫颈粘膜中性粒细胞的功能活性异常,但细胞产生活性氧的能力没有改变。这一发现可能是由于细胞内杀伤的氧非依赖性机制的普遍存在,因此表明中性粒细胞在局部水平上对孕妇免疫耐受平衡受损有一定作用。
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引用次数: 0
Mucosal immunity during rehabilitation in the patients after coronavirus infection 冠状病毒感染患者康复期间的黏膜免疫
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1190-mid
A. Khasanova, M. Kostinov, I. Soloveva
Following the coronavirus infection, a variety of symptoms may persist for a long time. Therefore, an important area of further research is to study the state and response of protective immune mechanisms in the post-COVID period. Our aim was to evaluate the dynamics of mucosal immunity by measuring sIgA in the saliva samples and nasal swabs (sIgA, lactoferrin), as well as efficiency of interferon-alpha-2b (IFNa2b) treatment in the patients after coronavirus infection. A study was conducted in the patients aged 18 to 60 years (n = 130) at the terms of 1 to 9 months after a coronavirus infection. A control group consisted of conditionally healthy individuals (n = 15). Diagnosis of post-COVID manifestations was carried out by collecting complaints, anamnestic data, physical examination and questionnaire. The state of mucosal immunity in saliva samples and nasopharyngeal mucosal scrapings was evaluated in dynamics as based on determination of sIgA and lactoferrin concentrations by means of enzyme immunoassay techniques prior to administration of local preventive therapy with recombinant IFNa2b, and 1 month after the treatment (VIFERON gel applied intranasally twice a day for 30 days). The following symptoms of post-COVID syndrome were documented In the study group: joint and muscular pain, shortness of breath, cough, fatigue and weakness, headache and dizziness, anxiety. In the group of patients who received preventive therapy during 1 to 3 months after coronavirus infection, a significantly increased level of saliva sIgA was noted, respectively, 1.840.28 to 5.781.96 mg/mL. As based on the data obtained with scrapings from nasopharyngeal mucosa, a significant increase in the level of sIgA was revealed in the group subjected to therapy up to 3 months after COVID-19 infection, i.e., from 28.613.0 to 39.833.85 mg/mL. In the group of patients devoid of preventive therapy, a stable maintenance of the reduced mucosal immunity parameters was found in all time intervals during the period of convalescence. In all observed patients, regardless of the group, a decreased lactoferrin level was found, being two-fold lower than the normal reference values. The incidence of respiratory viral infections in the group without preventive therapy was statistically significant, being registered in 9.2% of cases. Patients after COVID-19 infection exhibit a persistent decrease in mucosal immunity. Immunological efficacy was observed when using IFNa2b, thus making it possible to recommend it for rehabilitation in this group of patients over the period of convalescence.
冠状病毒感染后,各种症状可能会持续很长时间。因此,研究新冠病毒感染后保护性免疫机制的状态和反应是一个重要的研究领域。我们的目的是通过检测唾液样本和鼻拭子中的sIgA (sIgA,乳铁蛋白),以及干扰素- α -2b (IFNa2b)治疗在冠状病毒感染后的粘膜免疫动力学。对冠状病毒感染后1至9个月的18至60岁患者(n = 130)进行了一项研究。对照组由条件健康个体组成(n = 15)。通过收集投诉、记忆资料、体格检查和问卷调查对新冠肺炎后表现进行诊断。在给予重组IFNa2b局部预防治疗前和治疗后1个月(VIFERON凝胶每天鼻内两次,持续30天),通过酶免疫测定技术测定sIgA和乳铁蛋白浓度,对唾液样本和鼻咽粘膜刮擦物的粘膜免疫状态进行动态评估。研究组记录了以下新冠肺炎后综合征的症状:关节和肌肉疼痛、呼吸短促、咳嗽、疲劳和虚弱、头痛和头晕、焦虑。在冠状病毒感染后1 ~ 3个月接受预防治疗的患者中,唾液sIgA水平分别为1.840.28 ~ 5.781.96 mg/mL,显著升高。根据鼻咽黏膜刮片采集的数据,在新冠病毒感染后3个月,治疗组sIgA水平显著升高,即从28.613.0上升到39.833.85 mg/mL。在未进行预防治疗的患者组中,在恢复期的所有时间间隔内,粘膜免疫参数均稳定维持。在所有观察到的患者中,无论是哪一组,乳铁蛋白水平都下降,比正常参考值低两倍。未进行预防治疗组的呼吸道病毒感染发生率有统计学意义,为9.2%。COVID-19感染后患者黏膜免疫力持续下降。使用IFNa2b观察到免疫效果,因此有可能推荐该组患者在恢复期进行康复治疗。
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引用次数: 0
Effect of cucurbiturils on cytokine production by peripheral blood mononuclear cells of healthy donors 葫芦酚对健康供者外周血单核细胞产生细胞因子的影响
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1183-eoc
A. Aktanova, E. Kovalenko, E. Pashkina
Many drug delivery systems are currently under study, e.g., nanosized cavitands cucurbiturils, which, due to the presence of a cavity, can incorporate drug molecules. Since the immune system is quite sensitive to influence of nanomaterials and other cell-damaging factors, it is necessary to study immunosafety of the new delivery systems, i.e., immunotoxicity and immunomodulatory properties. The aim of this study was to investigate the effect of nanosized cucurbituril cavitands on the cytokine-producing ability of peripheral blood mononuclear cells in apparently healthy donors. Blood mononuclear cells (106/mL) were cultured in the presence of cucurbiturils at the following concentrations: 0.3 mM cucurbit[6]uril, 0.3 mM cucurbit[7]uril, and 0.01 mM cucurbit[8]uril for 72 h, under additional stimulation with aCD3 antibodies (1 g/mL), or without it. The level of cytokines in the supernatants was determined using enzyme immunoassay. It was shown that cucurbit[6]uril increased the level of spontaneous IL-4 production by 1.5 times (p 0.01) compared with the control. In the case of stimulated cytokine production, we found that cucurbit[6]uril reduced the level of IL-6, and also shows a tendency (p = 0.09) towards an increase in the IL-4 level. When cells were cultured with cucurbit[7]uril, we gave revealed a trend for increased production of pro-inflammatory TNF. It was also found that cucurbit[7]uril is able to suppress the production of IL-10 in aCD3-stimulated cell culture by 1.5 times. Cucurbit[8]uril was shown to inhibit production of cytokines in non-stimulated cell cultures. A significant decrease in the level of IFN and IL-10 was revealed as compared with the production of these cytokines in control cultures. When assessing the effect of cucurbit[8]uril on the IFN production upon stimulation with aCD3 antibodies, no significant differences were found, but there is also a trend for a decreased concentration of this cytokine agains control levels. Cucurbiturils can influence both spontaneous and stimulated production of cytokines by the blood mononuclear cells. The effect on cytokine-producing ability of the cells depends on the tested homologue compound.
许多药物传递系统目前正在研究中,例如,纳米尺度的空腔葫芦,由于空腔的存在,可以结合药物分子。由于免疫系统对纳米材料和其他细胞损伤因素的影响非常敏感,因此有必要研究新的递送系统的免疫安全性,即免疫毒性和免疫调节特性。本研究的目的是研究纳米葫芦比妥利空腔体对表面健康供者外周血单核细胞产生细胞因子能力的影响。将血单个核细胞(106个/mL)在葫芦素存在下以以下浓度培养:0.3 mM葫芦素[6]、0.3 mM葫芦素[7]和0.01 mM葫芦素[8],分别在aCD3抗体(1 g/mL)或不加aCD3抗体的刺激下培养72小时。酶免疫法测定上清液中细胞因子水平。结果表明,与对照相比,葫芦[6]脲可使自发IL-4生成水平提高1.5倍(p 0.01)。在刺激细胞因子产生的情况下,我们发现瓜类[6]uril降低了IL-6的水平,同时也显示出IL-4水平升高的趋势(p = 0.09)。当用葫芦籽[7]培养细胞时,我们发现促炎TNF的产生有增加的趋势。还发现葫芦[7]能抑制acd3刺激细胞培养1.5倍的IL-10的产生。葫芦[8]在非刺激细胞培养中被证明可以抑制细胞因子的产生。与对照培养中这些细胞因子的产生相比,IFN和IL-10的水平显着下降。在评估葫芦[8]对aCD3抗体刺激下IFN产生的影响时,没有发现显著差异,但也有这种细胞因子浓度低于对照水平的趋势。葫芦素可以影响血液单核细胞自发和刺激细胞因子的产生。对细胞产生细胞因子能力的影响取决于所测试的同源化合物。
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Russian Journal of Immunology
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