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Complicated ways of diagnosing common variable immune deficiency (case report) 常见可变免疫缺陷的复杂诊断方法(附1例报告)
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1173-cwo
O. Moskalets
Common variable immunodeficiency (CVID) is one of the most frequent forms of primary immunodeficiencies with predominant antibody deficiency. Unlike most other primary immunodeficiencies, this variant often manifests in adults thus creating certain difficulties in its detection. Manifestations of common variable immune deficiency are very diverse: infectious syndrome (respiratory tract infections, septic arthritis), diarrheal clinical pattern of both infectious and non-infectious genesis, autoimmune syndrome (autoimmune cytopenias, systemic rheumatic diseases), lymphoproliferative syndrome (benign lymphoid proliferation, lymphomas), interstitial lung disease and sarcoidosis-like granulomatous changes are quite common. Due to the lack of a distinct clinical pattern, the common variable immunodeficiency is often diagnosed too late. Such patients are observed for a long time by various specialists, and the absence of pathogenetic therapy (intravenous immunoglobulins) leads to steady progression of the disease and, often, to lethal outcome. The article presents a clinical observation illustrating the difficulties in making this diagnosis. A woman hospitalized with pneumonia presented with a mass in colonic submucosa. After excluding tuberculosis and lymphoma, a diagnosis of colon lipoma was made on the basis of histological examination. A few years later, the patients submandibular lymph nodes were periodically enlarged. Upon repeated histological examination, the diagnosis of granulomatous necrotizing lymphadenitis was established, the patient was referred to a rheumatologist to rule out systemic vasculitis. This diagnosis was not confirmed, but further examination revealed a sharp decrease in the gamma fraction of serum proteins. Therefore, an immunologists counseling was recommended to rule out immunodeficiency. The following blood serum analysis revealed an extremely low IgG and IgM content, with absence of detectable immunoglobulin A. On the basis of these findings, the diagnosis of common variable immune deficiency was made for the first time. Replacement therapy with high-dose intravenous immunoglobulins with control of pre-transfusion Ig levels was recommended, with further transition to a supporting treatment schedule. Hence, one may state that general practitioners are still poorly aware of primary immunodeficiencies, especially if non-infectious manifestations dominating in the clinical pattern. Routine analysis of total protein content and protein fractions can provide information that allows to suspect deficiency of antibodies and, therefore, to assess contents of distinct serum immunoglobulins in order to confirm CVID diagnosis.
常见的可变免疫缺陷(CVID)是一种最常见的原发性免疫缺陷,主要是抗体缺乏。与大多数其他原发性免疫缺陷不同,这种变异通常在成人中表现出来,因此在检测上存在一定的困难。常见变异性免疫缺陷的表现非常多样:感染性综合征(呼吸道感染、脓毒性关节炎)、感染性和非感染性腹泻的临床表现、自身免疫性综合征(自身免疫性细胞减少症、系统性风湿病)、淋巴细胞增生性综合征(良性淋巴细胞增生、淋巴瘤)、间质性肺疾病和结节病样肉芽肿改变非常常见。由于缺乏明确的临床模式,常见的可变免疫缺陷常常诊断得太晚。不同的专家对这些患者进行了长时间的观察,由于缺乏病原治疗(静脉注射免疫球蛋白),导致疾病稳步发展,往往导致致命的结果。本文提出了一个临床观察,说明了作出这种诊断的困难。一位因肺炎住院的妇女在结肠粘膜下层出现肿块。排除结核和淋巴瘤后,根据组织学检查诊断为结肠脂肪瘤。几年后,患者的下颌淋巴结周期性肿大。经反复组织学检查,诊断为肉芽肿性坏死性淋巴结炎,患者转至风湿病专家排除系统性血管炎。这一诊断未得到证实,但进一步检查显示血清蛋白γ分数急剧下降。因此,建议免疫学家咨询排除免疫缺陷。随后的血清分析显示IgG和IgM含量极低,缺乏可检测的免疫球蛋白a。根据这些发现,首次诊断为常见的可变免疫缺陷。建议使用高剂量静脉注射免疫球蛋白替代治疗,控制输血前Ig水平,并进一步过渡到支持治疗计划。因此,有人可能会说,全科医生仍然很少意识到原发性免疫缺陷,特别是如果非感染性表现在临床模式中占主导地位。常规分析总蛋白含量和蛋白组分可提供怀疑抗体缺乏的信息,从而评估不同血清免疫球蛋白的含量,以确认CVID的诊断。
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引用次数: 0
HBD1 and LL37 gene expression in children with atopic dermatitis HBD1和LL37基因在儿童特应性皮炎中的表达
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1194-hal
E. Bystritskaya, N. Murashkin, A. I. Materikin, E. Naumova, I. V. Yakovleva, N. Vartanova, O. Svitich
Atopic dermatitis (AD) is a multifactorial genetically determined inflammatory skin disease characterized by itching, chronic course, age-related features of localization and lesion morphology. Atopic dermatitis is caused by complex interactions between genetic, immunological, and environmental factors. The barrier function of the skin is impaired in atopic dermatitis. Antimicrobial peptides, e.g., LL-37, b-defensins are involved in maintaining the skin barrier function (especially, intercellular contacts). An imbalance of antimicrobial peptides may cause different disorders, including allergic pathologies. The aim of this study is to investigate gene expression profile of the HBD1 and LL37 encoding antimicrobial peptides in the samples of skin and blood mononuclear cells obtained from the children with moderate and severe atopic dermatitis before and after treatment. By means of real-time polymerase chain reaction, the levels of HBD1 and LL37 gene expression were evaluated in the samples. Statistical analysis showed significantly increased (p 0.017) expression levels of both HBD1 (H-test = 24.76; 2, n = 72; p = 0.00001), and LL37 genes (H-test = 15.69; 2, n = 72; p = 0.00039) in blood cells of AD patients compared to the control group, as well as decreased (p 0.05) levels of HBD1 expression in the affected skin compared to the control group. Our data on the cathelicidin gene in the skin do not differ from the literature data, since its expression is reduced in AD. In our series, an increase of the gene expression was revealed in PBMCs. The HBD1 peptide is expressed in both monocytes and macrophages, representing a link between innate and adaptive immunity. In our study, the expression of the HBD1 gene was increased only in blood, thus suggesting activation of innate immunity components at the systemic level in response to inflammation. Of importance, understanding the role of immunological markers in AD will help to develop novel prognostic approaches in management of the patients with atopic disorders. Therefore, one should understand pathogenetic mechanisms of allergic diseases.
特应性皮炎(AD)是一种多因素遗传决定的炎症性皮肤病,其特征是瘙痒、慢性病程、与年龄相关的定位特征和病变形态。特应性皮炎是由遗传、免疫和环境因素的复杂相互作用引起的。皮肤的屏障功能在特应性皮炎中受损。抗菌肽,如LL-37, b防御素参与维持皮肤屏障功能(特别是细胞间接触)。抗菌肽的失衡可能导致不同的疾病,包括过敏性疾病。本研究的目的是研究中、重度特应性皮炎患儿治疗前后皮肤和血液单个核细胞样本中编码抗菌肽的HBD1和LL37基因表达谱。通过实时聚合酶链反应检测HBD1和LL37基因的表达水平。统计学分析显示,两组患者HBD1表达水平均显著升高(p 0.017) (H-test = 24.76;2, n = 72;p = 0.00001), LL37基因(H-test = 15.69;2, n = 72;p = 0.00039),以及与对照组相比,受影响皮肤中HBD1表达水平降低(p 0.05)。我们关于皮肤中cathelicidin基因的数据与文献数据没有差异,因为它在AD中的表达减少。在我们的系列研究中,pbmc中基因表达增加。HBD1肽在单核细胞和巨噬细胞中均表达,代表先天免疫和适应性免疫之间的联系。在我们的研究中,HBD1基因的表达仅在血液中增加,这表明在炎症反应中,在全身水平上激活了先天免疫成分。重要的是,了解免疫标记物在AD中的作用将有助于开发新的治疗特应性疾病患者的预后方法。因此,应了解变态反应性疾病的发病机制。
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引用次数: 0
Phenotypic features of innate lymphoid cells in rheumatoid arthritis 类风湿关节炎先天淋巴样细胞的表型特征
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1184-pfo
O. Boeva, M. T. Berishvili, A. Sizikov, E. Pashkina
Currently, rheumatoid arthritis (RA) is considered among the most common autoimmune diseases worldwide, being associated with progressing disability, systemic organ and tissue lesions, as well as social and economic losses for the state. Studies of innate lymphoid cells (ILS) seems to be actual and significant when studying development of autoimmune inflammation in RA, in particular, the issues of the cell plasticity. ILC represent tissue resident lymphoid cells that display functional diversity, like as T cells. Moreover, ILC regulate orientation of immune response by means of cytokine production. Small amounts of ILCs are present in the bloodstream, presumably for migration to target organs and tissues. Accordingly, the study of ILC in RA will promote understanding of the RA pathogenesis. It is also possible in the future to develop new therapeutic strategies based on the impact on the immunological balance, as well as reducing the inflammatory process in RA. The aim of this study was to determine the subpopulation composition and phenotypic features of ILCs in RA. We have isolated and studied peripheral blood mononuclear cells (PBMC) from 7 patients with RA and 6 healthy donors. The isolated blood MNCs were stained with monoclonal antibodies conjugated to fluorochromes: lineage-specific (CD3/14/16/19/20/56) and anti-FceR1 alpha-FITC, anti-CD294-APC/Cy7, anti-CD127-PerCP/Cy5.5, anti-CD336-PE, anti-CD117-APC. ILCs were defined as Lin-CD127+. The numbers of CD294+ILCs (ILC2) were estimated in the general population, CD117-CD294-ILCs were defined as ILC1, and CD117+CD294-ILCs, as ILC3. The cell phenotype was analyzed with a FACS Canto II flow cytometer (BD Biosciences, USA). We determined relative numbers of different ILC subpopulations (ILC1, ILC2, and ILC3) among the total blood MNCs. It was shown, that the number of ILC2 cells in RA patients was statistically significantly reduced compared to healthy donors, whereas no significant differences in percentage of ILC1 and ILC3 were revealed between donors and patients. We also evaluated the amount of c-Kit+ILC2; there were no significant differences in the proportion of these cells between donors and patients. ILCs represent a population of cells that contribute to the RA pathogenesis. The role of ILC2 in RA is, presumably, protective. The ILC imbalance may contribute to the development of RA. For a better understanding of the RA pathogenesis, further studies of the subpopulation profile, phenotypic and functional characteristics of ILC are required in this disorder.
目前,类风湿性关节炎(RA)被认为是世界范围内最常见的自身免疫性疾病之一,与进行性残疾、系统性器官和组织病变以及国家的社会和经济损失有关。先天淋巴样细胞(innate lymphoid cells, ILS)的研究对于研究RA自身免疫性炎症的发生,特别是细胞的可塑性问题具有现实和重要意义。ILC代表具有功能多样性的组织常驻淋巴样细胞,如T细胞。此外,ILC还通过细胞因子的产生调节免疫应答的定向。少量的白细胞介素存在于血液中,可能是为了迁移到目标器官和组织。因此,研究ILC在RA中的作用将促进对RA发病机制的认识。未来也有可能根据对免疫平衡的影响开发新的治疗策略,以及减少RA的炎症过程。本研究的目的是确定类风湿关节炎中ILCs的亚群组成和表型特征。我们从7例RA患者和6例健康供者中分离和研究外周血单个核细胞(PBMC)。用荧光染料偶联的单克隆抗体对分离的血液MNCs进行染色:谱系特异性(CD3/14/16/19/20/56)和抗fcer1 α - fitc、抗cd274 - apc /Cy7、抗cd127 - percp /Cy5.5、抗cd336 - pe、抗cd117 - apc。ILCs定义为Lin-CD127+。在一般人群中估计CD294+ILCs (ILC2)的数量,将CD117-CD294-ILCs定义为ILC1,将CD117+CD294-ILCs定义为ILC3。用FACS Canto II流式细胞仪(BD Biosciences, USA)分析细胞表型。我们确定了总血液跨国公司中不同ILC亚群(ILC1, ILC2和ILC3)的相对数量。研究表明,与健康供者相比,RA患者的ILC2细胞数量有统计学意义上的显著减少,而供者和患者之间ILC1和ILC3的百分比无显著差异。我们还评估了c-Kit+ILC2的数量;在供者和患者之间,这些细胞的比例没有显著差异。ILCs代表了一群参与RA发病机制的细胞。ILC2在RA中的作用可能是保护性的。ILC失衡可能导致RA的发生。为了更好地了解RA的发病机制,需要进一步研究ILC在该疾病中的亚群特征、表型和功能特征。
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引用次数: 0
Clinical genetic counselling and rehabilitation treatment of a patient with Guillain–Barré syndrome after COVID-19 1例新型冠状病毒感染后格林-巴罗综合征患者的临床遗传咨询与康复治疗
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1166-cgc
N. Ponomareva, R. Koshelev, V. V. Lazarev, A. Kochetkov
The authors present a clinical case of rehabilitation after the development of GuillainBarr syndrome, an acute autoimmune inflammatory polyradiculoneuropathy, in a patient who underwent a SARS CoV-2 infection. The patient previously manifested with severe comorbidities (arterial hypertension, hypercholesterolemia, type 2 diabetes mellitus, stenosing atherosclerosis of brachiocephalic arteries). A diagnostic panel of single nucleotide gene polymorphisms associated with risk factors of cardiovascular diseases, metabolic disorders, immunopathology, pharmacogenetics was applied using PCR-RT Genetic Passport test system, and the results were interpreted in order to predict potential complications, adverse drug reactions and the choice of biomarkers for preventive measures. We have compared clinical manifestations, comorbid background and the identified genotype features, as follows: minor homo- and heterozygous variants of ACE, AGT, CYP1A2, NOS3, PPARD, EDN, PALLD, SNX19 genes associated with predisposition to cardiovascular diseases, increasing the risk of dysregulation of blood pressure, development of endothelial dysfunction. The following gene variants were revealed: FXII, ITGA2, ITGB3, MTHFR, MTRR, MTR, PAI-1 that increase the risk of venous and arterial thrombosis, along with gene variants of ADRB3, FTO, INSIG2, KCNG11, LEP, PPARD, TCF7L2, ApoC3, PON1 associated with carbohydrate and lipid metabolism disorders; polymorphisms in the genes determining the immune response, i.e., IL4, IL6, IL8, IL10, CDH1, BDNF1, CRP, CCR5 (with del32 allele considered a risk factor of severe SARS-CoV-2), homozygous polymorphism of a gene of FCGR2 associated with risk of antigen-antibody-complement-mediated cytotoxicity, circulation arrest, deposition of immune complexes in endothelium of microvessels, decreased antithrombotic effects and increased procoagulant activity. Pharmacogenetic study revealed a variant of the CYP4F2 gene, a CYP2C19 gene polymorphism associated with delayed metabolism of a number of pharmaceuticals which requires higher drug dosage, or choosing a drug with a different mechanism of action; gene variants of CYP1A2, GSTP1, GSTT1 reducing efficiency of the cellular detoxification system; NAT2*5 and NAT2*6 variants determining a decrease in appropriate enzyme activities when administering a standard dose of drugs with slowdown of their detoxification, accumulation of toxic metabolites causing clinical adverse effects (hepatotoxicity, dyspepsia, lupus-like syndrome, polyneuritis). Based on the genotype that determines pathogenesis of the multifactorial pathology (including immune-mediated complications of COVID-19), a personalized approach is recommended to the patient, in terms of treatment and prevention of complications. On the basis of testing the biochemical, immunological and blood coagulation biomarkers, an adequate choice of pharmaceuticals is recommended for the patient.
作者提出了一例临床病例,患者接受了SARS CoV-2感染,在发展为格林巴尔综合征(一种急性自身免疫性炎症性多根神经病变)后进行康复。患者既往表现出严重的合并症(动脉高血压、高胆固醇血症、2型糖尿病、头臂动脉狭窄性动脉粥样硬化)。采用PCR-RT基因护照检测系统,对心血管疾病、代谢紊乱、免疫病理、药物遗传学等危险因素相关的单核苷酸基因多态性进行诊断,并对结果进行解释,预测潜在并发症、药物不良反应和选择生物标志物进行预防措施。我们比较了临床表现、合并症背景和已确定的基因型特征,结果如下:ACE、AGT、CYP1A2、NOS3、PPARD、EDN、PALLD、SNX19基因的少量同型和杂合子变异与心血管疾病易感性相关,增加血压失调的风险,发生内皮功能障碍。发现以下基因变异:增加静脉和动脉血栓形成风险的FXII、ITGA2、ITGB3、MTHFR、MTRR、MTR、PAI-1,以及与碳水化合物和脂质代谢紊乱相关的ADRB3、FTO、INSIG2、KCNG11、LEP、PPARD、TCF7L2、ApoC3、PON1基因变异;决定免疫反应的基因多态性,即IL4、IL6、IL8、IL10、CDH1、BDNF1、CRP、CCR5 (del32等位基因被认为是严重SARS-CoV-2的危险因素),FCGR2基因的纯合多态性与抗原-抗体补体介导的细胞毒性、循环停滞、微血管内皮免疫复合物沉积、抗血栓作用降低和促凝活性增加的风险相关。药物遗传学研究发现CYP4F2基因变异,CYP2C19基因多态性与多种药物代谢延迟有关,这些药物需要更高的药物剂量,或选择不同作用机制的药物;CYP1A2、GSTP1、GSTT1基因变异降低细胞解毒系统效率;NAT2*5和NAT2*6变异体在给予标准剂量药物时,决定适当酶活性的降低,其解毒速度减慢,毒性代谢物的积累导致临床不良反应(肝毒性,消化不良,狼疮样综合征,多神经炎)。根据决定COVID-19多因素病理发病机制(包括免疫介导的并发症)的基因型,建议患者在治疗和预防并发症方面采取个性化方法。在检测生化、免疫和凝血生物标志物的基础上,为患者推荐适当的药物选择。
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引用次数: 0
Content of PD-1+ and PD-L1+ peripheral blood lymphocytes in individuals with pollen sensitization before and after allergen-specific immunotherapy 过敏原特异性免疫治疗前后花粉致敏个体外周血淋巴细胞PD-1+和PD-L1+含量的变化
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1192-cop
M. Barkovskaya, P. V. Sevastyanov, D. V. Demina, V. Kozlov
The available data on the contribution of the PD-1 and its ligands to immunoregulatory processes suggest their involvement into development of tolerance during immunotherapy. Currently, allergen-specific immunotherapy (ASIT) is the single treatment option that can influence the outcome of allergic diseases. Our purpose was to evaluate the PD-1/PD-L1 expression on the immune cells in patients with confirmed sensitization to plant pollen allergens in comparison with healthy controls before and after ASIT. The patients with bronchial asthma (BA) (n = 5, age 33.82.7), allergic rhinitis (AR) (n = 7, age 31.62.8), and healthy donors (n = 12, age 32.81.8) were included. Venous blood samples were obtained from the patients three times: before starting ASIT, upon completion of the ASIT course, and during the period of seasonal exacerbation. In patients with AR, the number of B lymphocytes was decreased, and the expression of PD-L1 by B lymphocytes increased after ASIT in comparison with donor parameters. At the same time, B lymphocyte counts were increased in BA patients before ASIT and returned to normal after ASIT. In AR, the CD8+PD-1+T lymphocyte count was reduced before ASIT, however, returning to normal values after ASIT was completed. Meanwhile, the reduced number of CD4+PD-1+T lymphocytes returned to normal only during the pollination season following ASIT. In BA patients, both before or after ASIT, PD-1 and PD-L1 expression on CD4+ and CD8+T lymphocytes did not differ from the donor parameters. The PD-1 expression in the T regulatory cells (Tregs) was decreased comparing with donors before ASIT in BA, and in the patients with AR, both before and after treatment. It was shown earlier that low PD-1 expression in the circulating CD4+ T cells is associated with high specific IgE concentrations. Thus, low PD-1 levels on CD4+ and CD8+T lymphocytes and regulatory T cells may indicate their functional disorders in allergic pathology. In summary, our results show a regulatory role of PD-1/PD-L1 axis in the immune response during ASIT and reflect differences in pathogenesis of allergic disorders, which are associated with imbalance of the cell activation and suppression. Further studies are required to establish the role of PD-1/PD-L1 interactions in the process of ASIT-induced modification of allergic responses.
PD-1及其配体对免疫调节过程的贡献的现有数据表明,它们参与免疫治疗期间耐受性的发展。目前,过敏原特异性免疫疗法(ASIT)是影响过敏性疾病预后的单一治疗选择。我们的目的是评估确认对植物花粉过敏原敏感的患者免疫细胞上PD-1/PD-L1的表达,并与健康对照者在ASIT前后进行比较。纳入支气管哮喘(BA)患者(n = 5,年龄33.82.7)、变应性鼻炎(AR)患者(n = 7,年龄31.62.8)和健康供者(n = 12,年龄32.81.8)。静脉血样采集三次:ASIT开始前、ASIT疗程结束后和季节性加重期间。在AR患者中,与供体参数相比,ASIT后B淋巴细胞数量减少,B淋巴细胞PD-L1表达增加。同时,BA患者在ASIT前B淋巴细胞计数升高,ASIT后B淋巴细胞计数恢复正常。在AR中,CD8+PD-1+T淋巴细胞计数在ASIT前减少,但在ASIT完成后恢复正常。同时,减少的CD4+PD-1+T淋巴细胞数量仅在ASIT后的授粉季节恢复正常。在BA患者中,在ASIT之前或之后,CD4+和CD8+T淋巴细胞上的PD-1和PD-L1表达与供体参数没有差异。治疗前后,与供者相比,BA患者和AR患者的T调节细胞(Tregs)中PD-1的表达均有所降低。早期研究表明,循环CD4+ T细胞中PD-1的低表达与高特异性IgE浓度有关。因此,CD4+和CD8+T淋巴细胞和调节性T细胞的低PD-1水平可能表明它们在过敏病理中的功能障碍。综上所述,我们的研究结果表明PD-1/PD-L1轴在ASIT期间的免疫反应中具有调节作用,反映了过敏性疾病发病机制的差异,这些差异与细胞激活和抑制的不平衡有关。需要进一步的研究来确定PD-1/PD-L1相互作用在asit诱导的过敏反应修饰过程中的作用。
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引用次数: 0
Experimental in vitro reprogramming of transformed phenotype of neutrophil granulocyte subpopulations in women with chronic recurrent infectious and inflammatory conditions of genital tract 生殖道慢性复发性感染和炎症妇女中性粒细胞亚群转化表型的体外重编程实验
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1205-eiv
S. Kovaleva, S. N. Pikturno, G. Chudilova, L. Lomtatidze, V. Krutova, V. Malinovskaya, I. Nesterova
Chronic inflammatory diseases of the pelvic organs (CIDPO) in women represent one of the urgent and insufficiently studied problems in gynecology across the world. These disorders are followed by adverse medical and socio-economic consequences, i.e., chronic local inflammatory process, chronic pelvic pain syndrome, ectopic pregnancy, infertility. Due to increasing chronicity and recurrence rates of genital infections and inflammatory diseases, there is a need for further studying the effector and regulatory mechanisms of immune system. Of special relevance are the studies of the receptor transformation in neutrophilic granulocytes (NG), the basic population of antimicrobial defense, with further substantiation of targeted immunomodulatory therapy. Purpose of the present study was to assess transformation of neutrophilic granulocytes from CD11b+CD64-CD32+CD16+ to that CD11b+CD64+CD32+CD16+ phenotype in immunocompromised women with CIDPO exacerbation, as well as to evaluate the possibility of in vitro reprogramming the neutrophile phenotype under the action of recombinant interferon (recIFN2b). Peripheral blood neutrophils were tested in the comparison group of 10 conditionally healthy women 20 to 40 years old, and in 17 women (20-40 years old) with the CIDPO exacerbation (group 1). The in vitro effect of recIFNa2b on the blood neutrophils was evaluated for 17 women with CIDPO (group 2). Flow cytometric technique (FCT, CYTOMICS FC500, Beckman Coulter, USA) was used to determine the number of NGs and cell receptor expression levels of neutrophilic CD11b+CD64-CD32+CD16+NG and CD11b+CD64+CD32+CD16+ subpopulations. In peripheral blood of women with CIDPO exacerbation, an increased expression density of surface membrane molecules was revealed by means of FCT: in the subpopulation CD11b+CD64-CD32+CD16+NG, CD16 proved to be 91.7% higher; in CD11b+CD64+CD32+CD16+NG subpopulation, CD16 was increased by 116%, and CD32 being higher by 81% against the comparison group. In the in vitro system, during the incubation of PB with recIFN2b (group 2), we have revealed an increased number of CD11b+CD64-CD32+CD16+ subpopulation relative to the comparison group and group 1, and significantly increased expression density of CD16 (by 212%); CD11b (by 56%), and CD32 (by 83%) than in comparison group, as well as higher density of CD16 expression by 163%; CD11b (by 223%) compared to group 1. The changes in expression density of membrane molecules was also detected by FCT for the activated subpopulation CD11b+CD64+CD32+CD16+NG, i.e., an increase in CD16 by 232% against control group, and decreased expression density of CD64 by 150% against the background, along with increased density of CD16 expression (by 54%), and CD11b (by 103%), relative to group 1, thus suggesting a reprogramming of negatively transformed NC phenotype. These findings may be considered a positive immunomodulatory effect providing a basis for further research in order to develop new integrated approaches t
女性盆腔器官慢性炎症性疾病(CIDPO)是世界范围内妇科领域亟待解决且研究不足的问题之一。这些疾病之后会产生不良的医疗和社会经济后果,即慢性局部炎症过程、慢性盆腔疼痛综合征、异位妊娠、不孕症。由于生殖器感染和炎症性疾病的慢性和复发率不断增加,需要进一步研究免疫系统的作用和调节机制。特别相关的是中性粒细胞(NG)受体转化的研究,这是抗菌防御的基本人群,进一步证实了靶向免疫调节治疗。本研究的目的是评估免疫功能受损女性CIDPO加重期中性粒细胞从CD11b+CD64-CD32+CD16+向CD11b+CD64+CD32+CD16+表型的转化,以及评估在重组干扰素(recIFN2b)作用下体外重编程中性粒细胞表型的可能性。对照组为10例20 ~ 40岁条件健康女性,对照组为17例20 ~ 40岁CIDPO加重女性(1组),体外观察recIFNa2b对17例CIDPO女性(2组)外周血中性粒细胞的影响。采用美国)测定中性粒细胞CD11b+CD64-CD32+CD16+NG和CD11b+CD64+CD32+CD16+亚群的NG数量和细胞受体表达水平。在CIDPO加重妇女的外周血中,FCT显示表面膜分子表达密度增加:在CD11b+CD64-CD32+CD16+NG亚群中,CD16高91.7%;在CD11b+CD64+CD32+CD16+NG亚群中,CD16比对照组升高了116%,CD32比对照组升高了81%。在体外系统中,在用recIFN2b孵育PB期间(2组),我们发现CD11b+CD64-CD32+CD16+亚群数量相对于对照组和1组增加,CD16的表达密度显著增加(212%);CD11b(56%)和CD32(83%)比对照组高,CD16表达密度高163%;CD11b(减少223%)。FCT还检测了活化亚群CD11b+CD64+CD32+CD16+NG的膜分子表达密度的变化,即CD16比对照组增加了232%,CD64的表达密度在背景下减少了150%,CD16的表达密度比1组增加了54%,CD11b的表达密度增加了103%,从而提示了负转化NC表型的重编程。这些发现可能被认为是一种积极的免疫调节作用,为进一步研究提供了基础,以便开发新的综合方法来治疗各种病因的CIDPO。
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引用次数: 0
Relationships between the factors of innate immune system and results of neurocognitive function parameters in the persons living with HIV infection: interim results of the study HIV感染者先天免疫系统因素与神经认知功能参数结果之间的关系:研究的中期结果
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1176-rbt
S. Knysh, L. F. Sklyar, Yu.S. Cherkasova, A. A. Chernikova, A. A. Knysh, T. Nevezhkina, E. Chagina
HIV infection is closely associated with damage to the nervous system, even despite usage of antiretroviral therapy. Thus, the patients are at a high risk for neurological complications. Due to limited permeability of the blood-brain barrier, the opportunity of its damage, both directly by the proteins of HIV-infected cells and indirectly, by immune system, e.g., inducing the production of inflammatory mediators, the involvement of the central nervous system in pathogenesis of HIV infection seems to be only a matter of time. HIV-associated neurocognitive disorders (HAND) comprise a poly-etiological pathological condition associated with direct and indirect damage to neurons in HIV infection. The role of interaction between the innate immune system and nervous system mediators in viral infections suggests that the specific changes in content and ratios of pro- and anti-inflammatory cytokines that are among the most polypotent mediators of immune regulation can be detectable in the persons prone to the development of HAND in HIV infection. The purpose of the present study was to characterize the features of serum content and the relationship between the indexes of innate immunity factors with the results of neurocognitive testing in the persons living with HIV. 123 persons were included in the study, of which 93 subjects live with HIV infection. They were divided into 3 groups according to the stages of HIV infection, according to the Russian Classification of HIV infection. 30 persons represented a group of healthy volunteers, comparable in age and gender with the members of main groups, and served as a control group. Determination of IL-1 and IL-10 contents in blood serum was carried out by solid-phase enzyme immunoassay. The level of CD4+T lymphocytes was determined by flow cytometry. Neurocognitive testing using Schulte tables, the Munsterberg test was conducted by a medical psychologist, according to generally accepted methods. A significant increase in the serum IL-10 content in subjects from the main groups was revealed as compared with the control group, as well as in group III compared with the values groups I and II. The levels of IL- 1, CD4+T lymphocytes were significantly lower in group III, compared with all other groups. The personal performance index determined by testing with Schulte tables was reduced in all groups, relative to the controls, with a significant predominance of the results in groups I and II over the results of the participants from group III. The scores in Munsterberg test were equally diminished in all the main groups compared to the control values. When assessing the Spearman coefficient, the presence of various correlation profiles was established, depending on the stage of the disease.
即使使用抗逆转录病毒治疗,艾滋病毒感染仍与神经系统损伤密切相关。因此,患者出现神经系统并发症的风险很高。由于血脑屏障的渗透性有限,其损伤的机会,直接由HIV感染细胞的蛋白质或间接由免疫系统,如诱导炎症介质的产生,中枢神经系统参与HIV感染的发病机制似乎只是一个时间问题。HIV相关神经认知障碍(HAND)包括与HIV感染中神经元直接和间接损伤相关的多病因病理状况。先天免疫系统和神经系统介质之间的相互作用在病毒感染中的作用表明,亲炎性和抗炎性细胞因子的含量和比例的特定变化是最多能的免疫调节介质之一,可以在HIV感染中容易发生HAND的人群中检测到。本研究的目的是了解HIV感染者血清含量的特点以及先天免疫因子指标与神经认知测试结果的关系。123人参与了这项研究,其中93人感染了艾滋病毒。根据俄罗斯艾滋病毒感染分类,他们根据感染阶段分为三组。30人代表一组健康的志愿者,年龄和性别与主要群体成员相当,并作为对照组。采用固相酶免疫法测定血清中IL-1和IL-10的含量。流式细胞术检测CD4+T淋巴细胞水平。神经认知测试使用舒尔特表,明斯特伯格测试由医学心理学家根据普遍接受的方法进行。与对照组相比,主要组受试者血清IL-10含量显著升高,III组受试者血清IL-10含量较I组和II组显著升高。与其他各组相比,III组IL- 1、CD4+T淋巴细胞水平明显降低。与对照组相比,通过舒尔特表测试确定的个人绩效指数在所有组中都有所降低,其中I组和II组的结果明显优于III组参与者的结果。与对照组相比,所有主要组的明斯特伯格测验得分均有相同的下降。当评估斯皮尔曼系数时,根据疾病的分期,建立了各种相关概况。
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引用次数: 0
Studies of CD45+ and CD46+ expression on the peripheral blood lymphocyte subsets of the post-COVID patients 新冠肺炎后患者外周血淋巴细胞亚群CD45+和CD46+表达的研究
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1160-soc
M. Dobrynina, A. Zurochka, M. Komelkova, S. Luo, V. Zurochka, H. Desheng, L. Ryabova, Alexey Sarapultsev
The SARS-CoV-2 virus can enter the cells using S1 viral spike (S) protein, not only by binding to ACE2, but also through other cellular receptors. These candidate receptors include CD46, which, like CD45, belongs to pan-leukocyte receptors and is expressed on all types of lymphocytes. In turn, SARS-CoV-2 infection is accompanied by damage to almost all compartments of the immune system, mainly T lymphocytes. The purpose of the study was to evaluate the expression levels of CD45+ and CD46+ in various subpopulations of lymphocytes in patients who had undergone SARS-CoV-2 infection. 72 patients who had undergone SARS-CoV-2 infection were examined. Using flow cytometry technique, we determined CD45+ and CD46+ (panleukocyte marker for lymphocyte gating), CD45+ and CD46+, CD3+ (T lymphocytes), CD45+ and CD46+, CD3+, CD4+ (helper inducers), CD45+ and CD46+, CD3+, CD8+ (cytotoxic T-lymphocytes), CD45+ and CD46+, CD3+, CD56+ (TNK cells) CD45+ and CD46+, CD3-, CD56+ (natural killers), CD45+ and CD46+, CD3-, CD19+ (B lymphocytes), CD45+ and CD46+, CD3+, CD4+, CD25+ (activated helpers, early activation of lymphocytes), CD45+ and CD46+, CD3+, HLA-DR (activated T lymphocytes late activation of lymphocytes). Our studies have shown that a decrease in CD46+ expression in T lymphocytes (CD3+) is accompanied by similar decrease of its expression in cytotoxic T lymphocytes (CD3+, CD8+), TNK (CD3+, CD56+), as well as in helpers T carrying markers of early activation (CD3+, CD4+, CD25+). At the same time, the most pronounced decrease was observed both among total T lymphocytes and cytotoxic T cells. In these patients, the expression level of CD46+ in B lymphocytes was slightly increased. Recent data suggest that there is no involvement of CD46 receptor on B lymphocytes. Our data suggest that the SARS-CoV-2 virus may affect the CD46 receptor. Such exposure may lead to promotion of the long-COVID (post-COVID) symptoms in such patients, thus requiring new approaches to correction of these disorders.
SARS-CoV-2病毒可以通过S1病毒刺突(S)蛋白进入细胞,不仅可以结合ACE2,还可以通过其他细胞受体进入细胞。这些候选受体包括CD46,它和CD45一样,属于泛白细胞受体,在所有类型的淋巴细胞上表达。反过来,SARS-CoV-2感染伴随着几乎所有免疫系统的损伤,主要是T淋巴细胞。本研究的目的是评估SARS-CoV-2感染患者不同淋巴细胞亚群中CD45+和CD46+的表达水平。对72例SARS-CoV-2感染患者进行了检查。利用流式细胞术技术,我们检测了CD45+和CD46+(淋巴细胞门控的泛白细胞标记物)、CD45+和CD46+、CD3+ (T淋巴细胞)、CD45+和CD46+、CD3+、CD8+(细胞毒性T淋巴细胞)、CD45+和CD46+、CD3+、CD56+ (TNK细胞)、CD45+和CD46+、CD3-、CD56+(自然杀伤细胞)、CD45+和CD46+、CD3-、CD19+ (B淋巴细胞)、CD45+和CD46+、CD3+、CD4+、CD25+(活化辅助细胞,早期活化淋巴细胞)、CD45+和CD46+、CD3+、CD4+、CD3+、CD45+和CD46+、CD3+、CD25+、CD45+和CD46+、CD3+、CD3+、CD25+(活化辅助细胞)、CD45+和CD46+、CD3+、CD3+、CD25+、CD45+和CD46+、HLA-DR(活化T淋巴细胞)。我们的研究表明,T淋巴细胞(CD3+)中CD46+表达的降低伴随着其在细胞毒性T淋巴细胞(CD3+, CD8+), TNK (CD3+, CD56+)以及辅助T携带早期激活标记(CD3+, CD4+, CD25+)中的表达的类似降低。同时,在总T淋巴细胞和细胞毒性T细胞中均观察到最明显的下降。在这些患者中,B淋巴细胞中CD46+的表达水平略有升高。最近的研究表明,B淋巴细胞上没有CD46受体的参与。我们的数据表明,SARS-CoV-2病毒可能影响CD46受体。这种暴露可能导致这些患者的长期covid(后covid)症状加剧,因此需要新的方法来纠正这些疾病。
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引用次数: 0
Dynamics of immune system parameters in development of SARS-CoV-2-specific immunity in a patient with common variable immune deficiency 常见可变免疫缺陷患者sars - cov -2特异性免疫发展过程中免疫系统参数的动态变化
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1163-doi
L. Sizyakina, I. Andreeva, M. Kharitonova
With the accumulation of data on the evolving SARS-CoV-2 infection pandemic, it became clear that the risk factors for severe course of COVID-19 among the patients with primary immunodeficiency include disorders associated with dysregulation of the immune response. In this regard, it is of interest to identify possible predictors of the pronounced inflammatory reaction upon infection with coronavirus in the patients with general variable immune insufficiency. For this purpose, the dynamics of immune system parameters was studied in a patient with CVID who underwent a severe clinical variant of COVID-19, as an example of clinical case. We present patient K., 49 years old, with CVID diagnosis verified at the age of 35 years who received regular replacement therapy with IVIG. He suffered from COVID-19 in severe form, received anti-cytokine therapy and an additional course of IVIG during the treatment. He was discharged in satisfactory condition. The quantitative and functional parameters of the T and B lineages of immune system were evaluated by flow cytofluorimetry during routine examinations before the infection and three months after the discharge from the hospital after COVID-19. It has been shown that, before the disease, there were changes in the parameters of B cells characteristic of CVID manifesting as a decrease in switched-memory B cells and plasmoblasts. Alterations in the T cell subsets were also revealed, as redistribution of the subpopulation composition towards T effectors with an increased cytolytic potential of these cells and a weakening of T cell suppression, due to decreased Treg in peripheral blood. After undergoing COVID-19, the patient developed specific IgM and IgG antibodies. The development of immune response was accompanied by an increase in the number of un-switched and switched memory B cells. At the same time, we have registered an increase in memory T cells ready for the proliferative response of T helper cells and Treg cells. The initial pro-inflammatory pattern of the T cell lineage system in our patient with CVID is explained by the implementation of the compensatory capabilities of the immune system, thus leading to activation of the cytolytic effects of cellular compartment in adaptive immune response, along with attenuation of the humoral component. Moreover, it is likely that these changes contributed to the clinical course of COVID-19 in this clinical case. Development of a specific humoral response to SARS-CoV-2 in a patient with CVID after a COVID-19 infection is accompanied by an increased proportion of memory B cells, coordinated dynamics of T cell suppression and activation parameters.
随着不断发展的SARS-CoV-2感染大流行数据的积累,原发性免疫缺陷患者中严重的COVID-19病程的危险因素变得清晰起来,包括与免疫反应失调相关的疾病。在这方面,确定一般可变免疫功能不全患者感染冠状病毒后明显炎症反应的可能预测因素是有意义的。为此,我们以临床病例为例,研究了一例CVID患者的免疫系统参数动态,该患者经历了COVID-19的严重临床变异。我们报告患者K., 49岁,在35岁时确诊为CVID,并接受常规IVIG替代治疗。他患有严重的COVID-19,在治疗期间接受了抗细胞因子治疗和额外的IVIG疗程。他出院时情况令人满意。采用流式细胞荧光法测定感染前常规检查和出院后3个月免疫系统T、B谱系定量及功能参数。研究表明,在发病前,CVID特有的B细胞参数发生了变化,表现为开关记忆B细胞和浆母细胞的减少。T细胞亚群的改变也被揭示出来,由于外周血中Treg的减少,亚群组成向T效应物重新分布,这些细胞的细胞溶解潜力增加,T细胞抑制减弱。在感染COVID-19后,患者产生了特异性IgM和IgG抗体。免疫应答的发展伴随着未开关和开关记忆B细胞数量的增加。与此同时,我们已经记录到记忆T细胞的增加,为T辅助细胞和Treg细胞的增殖反应做好了准备。在我们的CVID患者中,T细胞谱系系统的初始促炎模式可以通过免疫系统代偿能力的实现来解释,从而导致适应性免疫反应中细胞室的细胞溶解作用的激活,以及体液成分的衰减。此外,在该临床病例中,这些变化可能对COVID-19的临床病程有影响。COVID-19感染后CVID患者对SARS-CoV-2的特异性体液反应的发展伴随着记忆B细胞比例的增加,T细胞抑制和激活参数的协调动力学。
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引用次数: 0
Features of immune status in children with Wilson–Konovalov disease at different stages of liver fibrosis Wilson-Konovalov病患儿肝纤维化不同阶段的免疫状态特征
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1193-foi
O. Kurbatova, D. Kuptsova, L. M. Bezrukavnikova, T. Radygina, G. Movsisyan, A. Anushenko, A. D. Komarova, A. Potapov, S. Petrichuk, A. Fisenko
The pathology in WilsonConovalov disease (WCD) results from impaired excretion of copper, thus leading to its excessive accumulation in tissues. Hypercupreniluria is characteristic to the WCD. Toxic effects of copper on liver tissue can manifest as fatty degeneration of hepatocytes, hepatitis, fibrosis and cirrhosis. Purpose of the present work was as follows: estimation of immune status in children with WD depending on the stage of liver fibrosis. Fifty-three patients with WCD aged 6 to 18 years, were examined. The stage of liver fibrosis was assessed by transient liver elastography using FibroScan F502 (EchoSence, France). The immune status of peripheral blood lymphocytes was examined using CYTOMICS FC500 flow cytofluorimeter (Beckman Coulter, USA). The relative numbers of B lymphocytes (B1 and B2 populations), NK cells, T helper cells, cytotoxic T lymphocytes, Th17 lymphocytes, regulatory T cells, activated T helper cells were assessed in the lymphoid area. All indices of the patients immune status were recalculated for percentage of deviation from the age-dependent reference values. Mass concentration of copper in daily urine was determined by atomic absorption method using AAnalyst 800 spectrometer. Statistical processing was performed by Statistica10.0 program. The WCD patients are characterized by an increase of Т helpers, regulatory Т cells, Th17 lymphocytes and activated Т helpers, along with decrease of cytotoxic Т lymphocytes and NK cells against normal levels. The number of B cells did not depend on the stage of liver fibrosis and was at the lower limit of normal range, or decreased. Upon increase of the liver fibrosis stage, the number of B1 lymphocytes increases and B2 lymphocytes become decreased. The urinary copper content in the examined patients varied from 19 to 835 g/day, being higher than the reference values in 88% of children, with median value of 175 g/day (71-330). A correlation between urinary copper concentration and degree of immune status deviation was revealed (R = 0.63): urinary copper concentration was increased when the number of Th17 lymphocytes, B1 lymphocytes and regulatory T cells became higher, and when the number of B2 lymphocytes decreased. A significant decrease in the population of cytotoxic T lymphocytes (p = 0.034) was observed in children with WCD in the presence of KaiserFleischer ring. Indexes of cellular immunity in children with WCD are an informative tool to assess the severity of liver damage.
WilsonConovalov病(WCD)的病理是由于铜的排泄受损,从而导致其在组织中的过度积累。高铜血症是WCD的特征。铜对肝组织的毒性作用可表现为肝细胞脂肪变性、肝炎、纤维化和肝硬化。本研究的目的是:根据肝纤维化的分期来估计WD患儿的免疫状态。对53例6 ~ 18岁WCD患者进行了检查。肝纤维化分期采用纤维扫描F502 (echosense,法国)瞬时肝弹性成像进行评估。采用美国Beckman Coulter公司的流式细胞荧光仪(CYTOMICS FC500)检测外周血淋巴细胞免疫状态。测定淋巴区B淋巴细胞(B1和B2群)、NK细胞、辅助T细胞、细胞毒性T淋巴细胞、Th17淋巴细胞、调节性T细胞、活化的辅助T细胞的相对数量。重新计算患者免疫状态的所有指标与年龄相关参考值的偏差百分比。采用AAnalyst 800光谱仪,原子吸收法测定日尿中铜的质量浓度。统计处理采用Statistica10.0程序进行。WCD患者的特点是Т辅助细胞、调节性Т细胞、Th17淋巴细胞和活化的Т辅助细胞增加,细胞毒性Т淋巴细胞和NK细胞相对正常水平下降。B细胞数量与肝纤维化分期无关,均处于正常范围的下限或减少。随着肝纤维化分期的增加,B1淋巴细胞数量增加,B2淋巴细胞数量减少。接受检查的患者尿铜含量在19 - 835 g/天之间,88%的儿童高于参考值,中位数为175 g/天(71-330)。尿铜浓度与免疫状态偏离程度呈正相关(R = 0.63):尿铜浓度随Th17淋巴细胞、B1淋巴细胞和调节性T细胞数量增多而升高,随B2淋巴细胞数量减少而升高。在KaiserFleischer环存在的WCD患儿中,细胞毒性T淋巴细胞数量显著减少(p = 0.034)。WCD患儿的细胞免疫指标是评估肝损害严重程度的信息工具。
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Russian Journal of Immunology
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