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Issues of specific in vitro allergological diagnosis of atopic conditions 特应性疾病的特异性体外过敏诊断问题
Pub Date : 2022-12-22 DOI: 10.46235/1028-7221-1156-ios
Anna A. Barilo, S. Smirnova, V. D. Belenyuk, A. Savchenko, A. Borisov
There is a steady increase in the prevalence of allergic diseases of atopic origin worldwide, e.g., atopic bronchial asthma (ABA) and atopic dermatitis (AD). Identification of a causally significant allergen in allergic patients is crucial for the diagnosis, therapy and prevention of allergic diseases. Korea has developed the Allergy-Q multiplex test to detect specific IgE. Allergy-Q is based on an immunoblotting method using a nitrocellulose membrane as a solid phase for allergen immobilization and can detect allergen-specific IgE simultaneously to 107 allergens. Our aim was to conduct a comparative analysis for detectable allergen-specific IgE antibodies to food, fungal, pollen, household, epidermal allergens in blood serum by immunoblotting method using the Allergy-Q test system in patients with atopic dermatitis, atopic bronchial asthma and psoriasis. The study included patients with atopic dermatitis (AD, group 1, n = 9), atopic bronchial asthma (ABA, group 2, n = 14) and psoriasis (PS, group 3, n = 17). The concentration of total immunoglobulin E and allergen-specific immunoglobulins of class E in blood serum to 32 most common food, fungal, pollen, household, epidermal allergens was determined by the immunoblotting method using the Allergy-Q test system (Korea). We have found that sensitization of atopic origin was observed in all patients with AD (n = 9), in 85.7% (n = 12) of patients with atopic bronchial asthma, and in 47.1% (n = 8) of patients with psoriasis. Polyvalent sensitization was shown to prevail in all groups of the examined persons. When studying the spectrum of sensitization to food allergens, a significantly increased frequency of positive reactions to cows milk protein was found in the group of patients with AAA as compared with AD and PS groups. Among all studied groups, sensitization to the Alternaria fungi was found at the highest frequency in the group of patients with ABA. Sensitization to ragweed pollen was very common in all groups of patients. Sensitization to household and epidermal allergens in the groups with AD and AAA was noted for all studied allergens with the highest positivity rates for the feline epithelium and dog dander. In the present study, the Allergy-Q system showed an agreement with preliminary data from a specific allergological examinations. This relationship suggests a potential for usage of the Allergy-Q immunoblotting method as a highly effective alternative to other in vitro tests for diagnosing atopy. An advantage of the Allergy-Q Multiplex Serum Allergen-Specific IgE Detection Kit is a short processing time, small amount of blood sample, and broader clinical information on the causative allergens.
在世界范围内,特应性过敏性疾病的患病率稳步上升,例如,特应性支气管哮喘(ABA)和特应性皮炎(AD)。在变态反应性疾病的诊断、治疗和预防中,鉴别变态反应性疾病患者的致应原是至关重要的。韩国已经开发出了检测特定IgE的过敏原- q多重检测方法。Allergy-Q是基于一种免疫印迹方法,使用硝化纤维素膜作为固相固定过敏原,可以同时检测107种过敏原的过敏原特异性IgE。我们的目的是利用Allergy-Q测试系统,采用免疫印迹法对特应性皮炎、特应性支气管哮喘和牛皮癣患者血清中可检测到的食物、真菌、花粉、家庭、表皮过敏原特异性IgE抗体进行比较分析。本研究纳入特应性皮炎(AD, 1组,n = 9)、特应性支气管哮喘(ABA, 2组,n = 14)、牛皮癣(PS, 3组,n = 17)患者。采用韩国Allergy-Q测试系统,采用免疫印迹法测定血清中对32种最常见的食物、真菌、花粉、家庭、表皮过敏原的总免疫球蛋白E和E类过敏原特异性免疫球蛋白的浓度。我们发现,所有AD患者(n = 9)、85.7% (n = 12)的特应性支气管哮喘患者和47.1% (n = 8)的牛皮癣患者均存在特应性致敏。多价致敏在所有被检查人群中普遍存在。在研究食物过敏原的致敏谱时,发现AAA组患者对牛奶蛋白的阳性反应频率明显高于AD组和PS组。在所有研究组中,发现对Alternaria真菌的致敏在ABA患者组中频率最高。豚草花粉致敏在所有患者中都很常见。在AD和AAA组中,所有研究的过敏原都对家庭和表皮过敏原敏感,其中猫上皮和狗皮屑的阳性率最高。在目前的研究中,过敏症- q系统显示出与特定过敏症检查的初步数据一致。这种关系表明,过敏症- q免疫印迹法作为诊断特应性的其他体外测试的高效替代方法的潜力。Allergy-Q多重血清过敏原特异性IgE检测试剂盒的优点是处理时间短,血液样本量少,对致敏原的临床信息更广泛。
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引用次数: 0
Changes in mucosal immunity of oral cavity upon tooth loss in patients with periodontal diseases 牙周病患者牙齿脱落后口腔黏膜免疫的变化
Pub Date : 2022-12-22 DOI: 10.46235/1028-7221-1151-cim
M. E. Malyshev, Camil A. Kerimkhanov, A. Iordanishvili, A. O. Bumai
Partial or complete loss of teeth occurs in elderly and senile people, caused, mainly, by chronic generalized periodontitis. At the same time, the impact of presence or absence of persisting teeth and periodontium, is practically not covered in the literature as a factor of balance in the oral cavity, including local immunity of the mucous membranes. Our work concerned the changes in local immunity of the oral cavity occuring with the loss of natural teeth. We have observed 45 elderly people who were divided into 3 study groups, i.e., without inflammatory periodontal pathology (1), with periodontitis (2) and with chronic periapical inflammatory processes in the absence of periodontal inflammation (3). In order to sanitize oral cavity before the upcoming dental prosthetics, the patients of study groups 2 and 3 underwent extraction of all teeth in the upper and lower jaws. Indices of local immunity of the oral cavity in the salivary fluid of patients were assessed before surgical sanitation of the oral cavity (before the teeth extraction) and 30-35 days after removal of the last tooth. We have measured the salivary levels of secretory immunoglobulin A (sIgA) as well as pro-inflammatory cytokines, i.e., interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor- (TNF), and anti-inflammatory cytokines, e.g., receptor antagonist of interleukin-1 (RAIL), interleukin-4 (IL-4), interleukin-10 (IL-10)), as well as contents of antimicrobial peptides in saliva (catelicidin LL-37 and alphadefensins 1-3 (HNP1-3). We have found that the development of inflammation in severe inflammatory periodontal diseases, in particular, chronic generalized periodontitis requiring tooth extraction for oral cavity sanitation is characterized by functional insufficiency of secretory immunity of the oral mucosa associated with decreased secretion of secretory immunoglobulin A and antimicrobial peptides of neutrophilic origin, as well as a shift in the salivary cytokine balance towards increased production of pro-inflammatory cytokines. Removal of teeth, as the main source of inflammation and the basis for maintenance of dysbiotic microbiome biofilm leads to elimination of inflammation and the restoration of immune balance in the oral cavity.
部分或全部牙齿脱落发生在老年人和老年人,主要是由慢性广泛性牙周炎引起的。同时,作为口腔平衡的一个因素,包括粘膜的局部免疫,存在或不存在的恒牙和牙周组织的影响在文献中几乎没有涉及。我们的工作是关于口腔局部免疫随天然牙的脱落而发生的变化。我们观察了45名老年人,将其分为3个研究组,即无炎症性牙周病理组(1),有牙周炎组(2)和无牙周炎症的慢性根尖周炎症过程组(3)。为了在即将进行的义齿修复手术前对口腔进行消毒,研究组2和研究组3的患者都进行了上下颌全部牙齿的拔除。在手术前(拔牙前)和拔除最后一颗牙后30-35天对患者唾液液进行口腔局部免疫指标的评估。我们测量了唾液中分泌性免疫球蛋白A (sIgA)和促炎细胞因子的水平,如白细胞介素-1 (IL-1)、白细胞介素-6 (IL-6)、白细胞介素-8 (IL-8)、肿瘤坏死因子(TNF)和抗炎细胞因子,如白细胞介素-1受体拮抗剂(RAIL)、白细胞介素-4 (IL-4)、白细胞介素-10 (IL-10),以及唾液中抗菌肽的含量(catelicidin LL-37和α防御素1-3 (HNP1-3))。我们发现,严重炎症性牙周病,特别是需要拔牙进行口腔卫生的慢性广泛性牙周炎,其炎症的发展以口腔黏膜分泌免疫功能不足为特征,与分泌性免疫球蛋白A和中性粒细胞来源的抗菌肽分泌减少有关。以及唾液细胞因子平衡向促炎细胞因子生产增加的转变。牙齿的拔除作为炎症的主要来源,是维持口腔内益生菌群生物膜的基础,导致口腔内炎症的消除和免疫平衡的恢复。
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引用次数: 0
Features of mucosal immunity in the development of periodontal diseases in patients with type II diabetes mellitus 2型糖尿病患者牙周病发生过程中的黏膜免疫特征
Pub Date : 2022-12-22 DOI: 10.46235/1028-7221-1165-fom
E. Markelova, Anna A. Golitsyna, Yuri V. Yugai, Yuri Y. Pervov, Victor K. Kovalchuk
Chronic generalized periodontitis takes one of the leading places in the structure of dental diseases. Inflammatory periodontal disease is one of the most common complications of diabetes. An important role in the progression of periodontitis in type II diabetes mellitus (T2DM) belongs to disorders of the immune system that affect the supportive/retaining complex of the tooth. Inflammation of periodontal tissues which occurs in the patients with carbohydrate metabolism disorders is characterized by a more severe course, which worsens the condition and quality of life of patients with T2DM thus leading to tooth loss. In this regard, the immunological aspects of developing periodontal pathology under conditions of carbohydrate metabolism disorders are of great interest. Purpose of our study included comparative assessment of local TNF, TNF, IFN, IL-1, IL- 12, IL-17A levels in patients with periodontitis with and without carbohydrate metabolism disorders (type II diabetes mellitus), as well as in patients with type II diabetes mellitus without signs of periodontitis. 127 patients were examined, aged 30 to 59 years. The patients were divided into 3 groups, i.e., group I included patients suffering from periodontitis of varying severity without known comorbidities (47 persons); Group II consisted of patients with T2DM and periodontitis of varying severity (49 persons); Group III included patients with T2DM without symptoms of periodontitis (30 persons). The control group consisted of 30 practically healthy volunteers, matched to the patients for age and sex. Saliva specimens were used for laboratory studies. The levels of TNF, TNF, IFN, IL-1, IL-12, IL-17А were determined by ELISA sandwich technique, with specific reagents purchased from RD Diagnostics Inc (USA). A significant increase in the IL-1, TNF, IFN and IL-17A levels was found in patients of all groups compared with controls. At the same time, the increased concentrations of IFN, IL-1, IL-17A correlated with increase in periodontitis severity in the patients of both groups. Decreased TNF levels in saliva samples were revealed in the patients from almost all groups, regardless of the periodontitis severity. Significantly increased levels of IL-12 (p40 subunit) were recorded in saliva of the persons from group II and III when compared with controls and the group without diabetes mellitus.
慢性广泛性牙周炎是口腔疾病结构中的主要疾病之一。炎症性牙周病是糖尿病最常见的并发症之一。在2型糖尿病(T2DM)牙周炎的进展中,一个重要的作用是免疫系统的紊乱,影响了牙齿的支持/保留复合体。碳水化合物代谢紊乱患者发生牙周组织炎症,其病程更为严重,使T2DM患者的病情和生活质量恶化,从而导致牙齿脱落。在这方面,在碳水化合物代谢紊乱的条件下发展牙周病理的免疫学方面是非常有趣的。本研究的目的是比较评估伴有和不伴有碳水化合物代谢紊乱(II型糖尿病)的牙周炎患者以及伴有和不伴有牙周炎症状的II型糖尿病患者的局部TNF、TNF、IFN、IL-1、IL- 12、IL- 17a水平。127例患者接受检查,年龄30 ~ 59岁。将患者分为3组:1组患者患有不同程度的牙周炎,无已知合并症(47人);II组包括不同程度的T2DM和牙周炎患者(49人);第三组包括无牙周炎症状的T2DM患者(30人)。对照组由30名实际健康的志愿者组成,他们与患者的年龄和性别相匹配。唾液标本用于实验室研究。采用ELISA夹心技术检测TNF、TNF、IFN、IL-1、IL-12、IL-17А的水平,特异试剂购自美国RD诊断公司。与对照组相比,各组患者IL-1、TNF、IFN、IL-17A水平均显著升高。同时,两组患者的IFN、IL-1、IL-17A浓度升高与牙周炎严重程度升高相关。无论牙周炎的严重程度如何,几乎所有组的患者唾液样本中TNF水平均有所下降。与对照组和非糖尿病组相比,II组和III组患者唾液中IL-12 (p40亚基)水平显著升高。
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引用次数: 0
Autoinflammatory undifferentiated syndrome 自身炎性未分化综合征
Pub Date : 2022-12-22 DOI: 10.46235/1028-7221-1100-aus
A. Tolstykh, L. Popova, Akmer A. Albakasova, Natalia N. Usenkova
Identification of primary immunodeficiencies (PID), distinction of their nosological forms and timely admoinistered therapy for this disorders frepresent topical problems of modern immunology. According to the PID registry of the National Association of Experts in the Field of Primary Immunodeficiencies (NAEPID), as of 2021, 3617 cases of this disease were diagnosed in Russian Federation (RF). The prevalence of PID in Russian Federation is 2.48 per 100,000 population. Currently, autoinflammatory syndromes (AIS) comprise rare, genetically determined disorders. According to the NAEPID registry data, of the PID register, 541 cases of autoinflammatory syndrome (AIS) were registered in the Russian Federation (2021). Timely diagnosis of AIS is especially important in young children who have similar phenotypic signs, in order to reduce the number of deaths and prevent disability. According to the PID registry, the median diagnostic delay in Russia is 27 months. The purpose of this work is to update information about the autoinflammatory syndrome that clinicians may encounter, e.g., pediatricians, rheumatologists, hematologists and other specialists. This syndrome requires a complex differential diagnostic algorithm for clinicians and is often subject to multidisciplinary approach, involving specialists of different profile. This article describes a clinical case of a 3-year-old child S. with a diagnosis of Primary immunodeficiency: autoinflammatory syndrome, undifferentiated. The patient was diagnosed since the age of 5 months, when periodic rises in body temperature to febrile values were registered once a month. Later on, the fever episodes were observed 2 times a month. The diagnosis was made at the place of residence as secondary immunodeficiency virus-associated state (CMV infection). CMV viremia was canceled against the background of ongoing treatment, but the inflammatory attacks persisted. Molecular genetic studies did not reveal any defects. In view of poor response to NSAID therapy and prednisone prescribed at a dose of 1-1.5 mg/kg/day, he was admitted to the Dmitry Rogachev Research Medical Cemter. The child was finally diagnosed with PID, and therapy was initiated with a selective competitive inhibitor of TNFa etanercept at a dose of 0.8 mg/kg/day once a week. Hence, the autoinflammatory syndrome in children is difficult to diagnose and select therapy, and it may be unfavorable prognostically.
原发性免疫缺陷(PID)的识别,其病状的区分和及时给药治疗这种疾病是现代免疫学的局部问题。根据全国原发性免疫缺陷领域专家协会(NAEPID)的PID登记,截至2021年,俄罗斯联邦(RF)诊断出3617例这种疾病。俄罗斯联邦的PID患病率为每10万人2.48例。目前,自身炎症综合征(AIS)包括罕见的、由基因决定的疾病。根据NAEPID登记数据,在PID登记中,俄罗斯联邦(2021年)登记了541例自身炎症综合征(AIS)。对于具有相似表型体征的幼儿,及时诊断AIS尤为重要,以减少死亡人数和预防残疾。根据PID登记,俄罗斯的诊断延迟中位数为27个月。这项工作的目的是更新临床医生可能遇到的自身炎症综合征的信息,例如儿科医生、风湿病学家、血液学家和其他专家。这种综合征需要临床医生使用复杂的鉴别诊断算法,通常需要多学科方法,涉及不同背景的专家。本文描述了一个3岁儿童s的临床病例,诊断为原发性免疫缺陷:自身炎症综合征,未分化。患者自5个月时确诊,每月记录一次体温周期性升高至发热值。此后每月发热2次。在居住地诊断为继发性免疫缺陷病毒相关状态(CMV感染)。巨细胞病毒血症在持续治疗的背景下被取消,但炎症攻击持续存在。分子遗传学研究未发现任何缺陷。鉴于对非甾体抗炎药治疗和处方剂量为1-1.5 mg/kg/天的强的松的不良反应,他被送入Dmitry Rogachev医学研究中心。该患儿最终被诊断为PID,治疗开始使用选择性竞争抑制剂TNFa依那西普,剂量为0.8 mg/kg/天,每周一次。因此,儿童自身炎症综合征很难诊断和选择治疗,并可能对预后不利。
{"title":"Autoinflammatory undifferentiated syndrome","authors":"A. Tolstykh, L. Popova, Akmer A. Albakasova, Natalia N. Usenkova","doi":"10.46235/1028-7221-1100-aus","DOIUrl":"https://doi.org/10.46235/1028-7221-1100-aus","url":null,"abstract":"Identification of primary immunodeficiencies (PID), distinction of their nosological forms and timely admoinistered therapy for this disorders frepresent topical problems of modern immunology. According to the PID registry of the National Association of Experts in the Field of Primary Immunodeficiencies (NAEPID), as of 2021, 3617 cases of this disease were diagnosed in Russian Federation (RF). The prevalence of PID in Russian Federation is 2.48 per 100,000 population. Currently, autoinflammatory syndromes (AIS) comprise rare, genetically determined disorders. According to the NAEPID registry data, of the PID register, 541 cases of autoinflammatory syndrome (AIS) were registered in the Russian Federation (2021). Timely diagnosis of AIS is especially important in young children who have similar phenotypic signs, in order to reduce the number of deaths and prevent disability. According to the PID registry, the median diagnostic delay in Russia is 27 months. The purpose of this work is to update information about the autoinflammatory syndrome that clinicians may encounter, e.g., pediatricians, rheumatologists, hematologists and other specialists. This syndrome requires a complex differential diagnostic algorithm for clinicians and is often subject to multidisciplinary approach, involving specialists of different profile. This article describes a clinical case of a 3-year-old child S. with a diagnosis of Primary immunodeficiency: autoinflammatory syndrome, undifferentiated. The patient was diagnosed since the age of 5 months, when periodic rises in body temperature to febrile values were registered once a month. Later on, the fever episodes were observed 2 times a month. The diagnosis was made at the place of residence as secondary immunodeficiency virus-associated state (CMV infection). CMV viremia was canceled against the background of ongoing treatment, but the inflammatory attacks persisted. Molecular genetic studies did not reveal any defects. In view of poor response to NSAID therapy and prednisone prescribed at a dose of 1-1.5 mg/kg/day, he was admitted to the Dmitry Rogachev Research Medical Cemter. The child was finally diagnosed with PID, and therapy was initiated with a selective competitive inhibitor of TNFa etanercept at a dose of 0.8 mg/kg/day once a week. Hence, the autoinflammatory syndrome in children is difficult to diagnose and select therapy, and it may be unfavorable prognostically.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85912698","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
Incidence of IgA antibodies specific to benzo[a]pyrene and steroid hormones in women with colorectal cancer and breast cancer 结直肠癌和乳腺癌女性中苯并[a]芘和类固醇激素特异性IgA抗体的发生率
Pub Date : 2022-12-22 DOI: 10.46235/1028-7221-1090-ioi
A. V. Averianov, A. Antonov, Alexey S. Zhivotovskiy, M. Kostyanko, I. Vafin, G. Kolpinskiy, A. Glushkov
Formation of DNA adducts of chemical carcinogens is a trigger for carcinogenesis. Adducts of benzo[a]pyrene metabolites and estradiol metabolites with DNA have been found in normal and tumor cells in healthy women and patients with breast and colorectal cancer. These low-weight compounds in macromolecular complexes induce the synthesis of specific antibodies. Previously, the presence of specific antibodies against benzo[a]pyrene (IgA-Bp), estradiol (IgA-Es) and progesterone (IgA-Pg) was revealed in breast cancer patients. The aim of this study is to identify the putative features of the IgA-Bp, IgA-Es, and IgA-Pg formation in postmenopausal women with colorectal cancer, in comparison with healthy and breast cancer patients. Using a noncompetitive enzyme-linked immunosorbent assay, the content of these antibodies was studied in the blood serum of healthy women (n = 401), patients with colorectal cancer (n = 219) and breast cancer (n = 1469) using conjugates of Bp, Es, and Pg with bovine serum albumin as adsorbed antigens. When compared with healthy people, the patients with colorectal cancer exhibited higher incidence of IgA-Bp 3 (75% vs 37%, p 0.0001, OR = 5.0), as well as more common levels of individual antibody ratios: IgA-Bp/IgA-Es 1 (82% vs 41%, p 0.0001, OR = 6.5); IgA-Bp/IgA-Pg 1.5 (77% vs 20%, p 0.0001, OR = 13.4); IgA-Es/IgA-Pg 1 (89% vs 48%, p 0.0001, OR = 8.7). In breast cancer patients, compared with healthy people, high IgA-Bp values ( 3) were more common (45% vs 37%, p 0.004, OR = 1.4), as well as increased IgA-Bp/IgA-Es ratio 1 (57% vs 41%, p 0.0001, OR = 1.9), IgA-Bp/IgA-Pg 1.1 (71% vs 36%, p 0.0001, OR = 4.4) and IgA-Es/IgA-Pg 1.1 (71% vs 41%, p 0.0001, OR = 3.5). In patients with colorectal cancer, compared with patients with breast cancer we have found higher incidence of increased IgA-Bp values ( 3) (75% vs 45%, p 0.0001), IgA-Es 3 (53% vs 39%, p 0, 0001), and of IgA-Pg 2 (52% vs 44%, p = 0.025), as well as IgA-Bp/IgA- Es 1 (82% vs 57%, p 0.0001, OR = 50.8 ); IgA-Bp/IgA-Pg 1.5 (77% vs 49%, p 0.0001); IgA-Es/IgA-Pg 1.1 (85% vs 71%, p 0.0001). The apparently high serum IgA-Bp levels reflect the formation of DNA-Bp adducts at large scale in target cells in colorectal cancer compared with healthy women and breast cancer patients, due to direct exposure of colon epithelium to Bp from food. Immunoassay for IgA-Bp, IgA-Es and IgA-Pg is proposed for assessing individual risk of colorectal cancer in postmenopausal women. The ratios of IgA Bp/IgA-Pg levels 1.5 represent the most informative marker of individual risk for colorectal cancer.
化学致癌物DNA加合物的形成是致癌的诱因。在健康妇女以及乳腺癌和结直肠癌患者的正常细胞和肿瘤细胞中发现了苯并[a]芘代谢物和雌二醇代谢物与DNA的加合物。这些在大分子复合物中的低质量化合物诱导特异性抗体的合成。此前,在乳腺癌患者中发现了针对苯并[a]芘(IgA-Bp)、雌二醇(IgA-Es)和黄体酮(IgA-Pg)的特异性抗体。本研究的目的是确定绝经后结直肠癌妇女中IgA-Bp、IgA-Es和IgA-Pg形成的推定特征,并与健康和乳腺癌患者进行比较。采用非竞争性酶联免疫吸附法,研究了健康女性(401)、结直肠癌患者(219)和乳腺癌患者(1469)血清中这些抗体的含量,将Bp、Es和Pg与牛血清白蛋白结合作为吸附抗原。与健康人群相比,结直肠癌患者表现出更高的IgA-Bp 3发病率(75% vs 37%, p 0.0001, OR = 5.0),以及更常见的个体抗体比率水平:IgA-Bp/IgA-Es 1 (82% vs 41%, p 0.0001, OR = 6.5);IgA-Bp/IgA-Pg 1.5 (77% vs 20%, p 0.0001, OR = 13.4);IgA-Es/IgA-Pg 1 (89% vs 48%, p 0.0001, OR = 8.7)。在乳腺癌患者中,与健康人群相比,高IgA-Bp值(3)更为常见(45% vs 37%, p 0.004, OR = 1.4), IgA-Bp/IgA-Es比值1 (57% vs 41%, p 0.0001, OR = 1.9)、IgA-Bp/IgA-Pg 1.1 (71% vs 36%, p 0.0001, OR = 4.4)和IgA-Es/IgA-Pg 1.1 (71% vs 41%, p 0.0001, OR = 3.5)升高。在结直肠癌患者中,与乳腺癌患者相比,我们发现IgA- bp值升高的发生率更高(3)(75% vs 45%, p 0.0001), IgA-Es 3 (53% vs 39%, p 0.0001), IgA- pg 2 (52% vs 44%, p = 0.025),以及IgA- bp /IgA- Es 1 (82% vs 57%, p 0.0001, OR = 50.8);IgA-Bp/IgA-Pg 1.5 (77% vs 49%, p 0.0001);IgA-Es/IgA-Pg 1.1 (85% vs 71%, p 0.0001)。与健康女性和乳腺癌患者相比,结直肠癌患者血清中IgA-Bp水平明显升高,反映了结肠癌患者的靶细胞中DNA-Bp加合物的大规模形成,这是由于结肠上皮直接暴露于食物中的Bp。IgA-Bp、IgA-Es和IgA-Pg的免疫测定被建议用于评估绝经后妇女结直肠癌的个体风险。IgA Bp/IgA- pg水平的比值为1.5,是个体结直肠癌风险的最有信息的标志。
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引用次数: 0
Cooperation of idiotypic and anti-idiotypic antibodies at the steroid-depended chemical carcinogenesis 独特型抗体和抗独特型抗体在类固醇依赖性化学癌变中的协同作用
Pub Date : 2022-12-22 DOI: 10.46235/1028-7221-1177-coi
E. Polenok, L. Gordeeva, Stella M. Mun, M. Kostyanko, A. Antonov, N. E. Verzhbitskaja, P. V. Bairamov, G. Kolpinskiy, I. Vafin, A. Glushkov
Immunological research of steroid-depended chemical carcinogenesis in humans is based on positive experience in the clinical usage of selective estrogen receptor modulators and experimental design of immunological methods for human protection from environmental carcinogens. Our study aimed for research of idiotypic antibodies against benzo[a]pyrene, estradiol and progesterone (IgA1-Bp, IgA1-E2 and IgA1-Pg), in connection with anti-idiotypic antibodies specific to estradiol and progesterone (IgG2-E2 and IgG2-Pg) in serum samples of postmenopausal healthy women (HW) and ER+/PR+ stage I breast cancer patients (BCP). Idiotypic antibodies were studied in 402 HW and 475 BCP using ELISA technique, with BP, E2 and Pg conjugated with bovine serum albumin as adsorbed antigens. The anti-idiotypic antibodies were studied using ELISA method and monoclonal antibodies against E2 and Pg as adsorbed antigens. High individual ratios of IgA1-Bp/ IgA1-Pg 1 and IgA1-E2/IgA1-Pg 1 were revealed in 42.1% and 48.5% HW, and in 71.1% and 78.1% of BCP cases (p 0.0001, OR = 5.9 and OR = 3.8, respectively). High IgG2-E2 4 levels were found in 23.4% HW and in 41.2% of BCP group (p = 0.0001, OR = 2.3). Combination of IgA1-Bp/IgA1-Pg 1 with IgG2-E2 4 and IgG2-Pg 2 was more common in HW, than in BCP (29.3% vs 5.8%, p 0.0001, OR = 0.1). Combinations of IgA1-Bp/IgA1-Pg 1with IgG2-E2 4 or with IgG2-Pg 2 were more frequent in BCP, than in HW (12.0% and 31.8% vs 4.9% and 15.2%, accordingly, p = 0.01, OR = 2.7 and p = 0.001, OR = 2.6), as well as combination of IgA1-Bp/IgA1-Pg 1 with IgG2-E2 4 and IgG2-Pg 2 (23.4% vs 9.8%, p = 0.0003, OR = 2.8). Similar specific features were found in HW and BCP when studying IgA1-E2/IgA1-Pg ratio with IgG2-E2 and IgG2-Pg. Nevertheless, high IgA1-Bp/IgA1-Pg 1 or IgA1-E2/IgA1-Pg 1 combined with low IgG2-E2 4 + IgG2-Pg 2 were revealed in HW (27.7% and 28.8%) more frequently, than in BCP (19.7%, p = 0.06 and 17.9%, p = 0.008). Excess of IgA1-Bp and IgA1-E2 levels over IgA1-Pg in combination with high IgG2-E2 and IgG2-Pg levels in HW is associated with ER+/PR+ BC stage I condition and may serve as an marker for preventive BC therapy by the targeted ER modulators.
人类类固醇依赖性化学致癌的免疫学研究是基于选择性雌激素受体调节剂临床应用的积极经验和人类免受环境致癌物侵害的免疫学方法的实验设计。本研究旨在研究绝经后健康妇女(HW)和ER+/PR+ I期乳腺癌患者(BCP)血清中抗苯并[a]芘、雌二醇和黄体酮的独特型抗体(IgA1-Bp、IgA1-E2和IgA1-Pg),以及抗雌二醇和黄体酮的独特型抗体(IgG2-E2和IgG2-Pg)。以BP、E2和Pg与牛血清白蛋白偶联为吸附抗原,采用ELISA技术研究了402 HW和475 BCP的独特型抗体。以E2和Pg单克隆抗体为吸附抗原,采用ELISA法研究其抗独特型抗体。IgA1-Bp/ IgA1-Pg 1和IgA1-E2/IgA1-Pg 1的个体比值在HW中分别为42.1%和48.5%,BCP中分别为71.1%和78.1% (p = 0.0001, OR = 5.9和OR = 3.8)。HW组和BCP组分别有23.4%和41.2%的IgG2-E2 - 4水平升高(p = 0.0001, OR = 2.3)。IgA1-Bp/IgA1-Pg 1与IgG2-E2 4和IgG2-Pg 2的结合在HW中比在BCP中更常见(29.3% vs 5.8%, p 0.0001, OR = 0.1)。IgA1-Bp/IgA1-Pg 1与IgG2-E2 4或与IgG2-Pg 2的联合在BCP中比在HW中更常见(分别为12.0%和31.8%,分别为4.9%和15.2%,p = 0.01, or = 2.7和p = 0.001, or = 2.6),以及IgA1-Bp/IgA1-Pg 1与IgG2-E2 4和IgG2-Pg 2的联合(分别为23.4%和9.8%,p = 0.0003, or = 2.8)。用IgG2-E2和IgG2-Pg研究IgA1-E2/IgA1-Pg比值时,发现HW和BCP具有相似的特异性特征。然而,高IgA1-Bp/IgA1-Pg 1或IgA1-E2/IgA1-Pg 1合并低IgG2-E2 4 + IgG2-Pg 2在HW中(27.7%和28.8%)比在BCP中(19.7%,p = 0.06和17.9%,p = 0.008)更为常见。在HW中,IgA1-Bp和IgA1-E2水平高于IgA1-Pg,同时IgG2-E2和IgG2-Pg水平高与ER+/PR+ BC I期疾病有关,可能作为靶向ER调节剂预防性BC治疗的标志。
{"title":"Cooperation of idiotypic and anti-idiotypic antibodies at the steroid-depended chemical carcinogenesis","authors":"E. Polenok, L. Gordeeva, Stella M. Mun, M. Kostyanko, A. Antonov, N. E. Verzhbitskaja, P. V. Bairamov, G. Kolpinskiy, I. Vafin, A. Glushkov","doi":"10.46235/1028-7221-1177-coi","DOIUrl":"https://doi.org/10.46235/1028-7221-1177-coi","url":null,"abstract":"Immunological research of steroid-depended chemical carcinogenesis in humans is based on positive experience in the clinical usage of selective estrogen receptor modulators and experimental design of immunological methods for human protection from environmental carcinogens. Our study aimed for research of idiotypic antibodies against benzo[a]pyrene, estradiol and progesterone (IgA1-Bp, IgA1-E2 and IgA1-Pg), in connection with anti-idiotypic antibodies specific to estradiol and progesterone (IgG2-E2 and IgG2-Pg) in serum samples of postmenopausal healthy women (HW) and ER+/PR+ stage I breast cancer patients (BCP). Idiotypic antibodies were studied in 402 HW and 475 BCP using ELISA technique, with BP, E2 and Pg conjugated with bovine serum albumin as adsorbed antigens. The anti-idiotypic antibodies were studied using ELISA method and monoclonal antibodies against E2 and Pg as adsorbed antigens. High individual ratios of IgA1-Bp/ IgA1-Pg 1 and IgA1-E2/IgA1-Pg 1 were revealed in 42.1% and 48.5% HW, and in 71.1% and 78.1% of BCP cases (p 0.0001, OR = 5.9 and OR = 3.8, respectively). High IgG2-E2 4 levels were found in 23.4% HW and in 41.2% of BCP group (p = 0.0001, OR = 2.3). Combination of IgA1-Bp/IgA1-Pg 1 with IgG2-E2 4 and IgG2-Pg 2 was more common in HW, than in BCP (29.3% vs 5.8%, p 0.0001, OR = 0.1). Combinations of IgA1-Bp/IgA1-Pg 1with IgG2-E2 4 or with IgG2-Pg 2 were more frequent in BCP, than in HW (12.0% and 31.8% vs 4.9% and 15.2%, accordingly, p = 0.01, OR = 2.7 and p = 0.001, OR = 2.6), as well as combination of IgA1-Bp/IgA1-Pg 1 with IgG2-E2 4 and IgG2-Pg 2 (23.4% vs 9.8%, p = 0.0003, OR = 2.8). Similar specific features were found in HW and BCP when studying IgA1-E2/IgA1-Pg ratio with IgG2-E2 and IgG2-Pg. Nevertheless, high IgA1-Bp/IgA1-Pg 1 or IgA1-E2/IgA1-Pg 1 combined with low IgG2-E2 4 + IgG2-Pg 2 were revealed in HW (27.7% and 28.8%) more frequently, than in BCP (19.7%, p = 0.06 and 17.9%, p = 0.008). Excess of IgA1-Bp and IgA1-E2 levels over IgA1-Pg in combination with high IgG2-E2 and IgG2-Pg levels in HW is associated with ER+/PR+ BC stage I condition and may serve as an marker for preventive BC therapy by the targeted ER modulators.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88936951","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
Prognosis of immune state following basic therapy and thymalin treatment in patients with severe COVID-19 infection 重症COVID-19感染患者基础治疗和胸腺苷治疗后免疫状态的预后
Pub Date : 2022-12-22 DOI: 10.46235/1028-7221-1209-poi
B. Kuznik, Yurii N. Smolyakov, K. Shapovalov, P. Tereshkov, V. A. Konnov, N. Chalisova
Significant changes in cellular and humoral immunity are observed in new coronavirus infection (COVID-19). The cytokine storm develops in cases of severe clinical course, being accompanied by significantly increased levels of pro-inflammatory cytokines, often associated with suppression of immune response. At the same time, the prediction of the immune status is an urgent task, thus allowing timely correction of current therapy. The aim of our research was to evaluate predictive capability for the immune system changes on the 6th day of COVID-19 disease when using standard therapy, or with addition of immunocorrector thymalin to the treatment regimen. A retrospective study was conducted in 87 patients with severe COVID-19. All patients were divided into 2 groups, i.e., (1) controls who received basic treatment; (2) basic treatment supplied with thymalin (10 mg, intramuscular injections daily for 5 days). Assessment of severity and clinical course of COVID-19, and basic treatment regimen for the patients corresponded to current version of the interim Guidelines from the Ministry of Health of the Russian Federation Prevention, diagnosis and treatment of a new coronavirus infection COVID-19. Laboratory studies included complete blood counts, immunogram parameters with the calculation of the ratio of certain types of leukocytes were performed on the 1st and 6th days of observation. Statistical evaluation was made using scripts of the specialized statistical analysis language R (http://cran.r-project.org) version 4.1.3. The blood parameters were evaluated using the binary classification method. The changes in parameters of cellular immunity were classified by means of ROC-analysis. We have found that the basic therapy of severely ill COVID-19 patients was not followed by recovery of immune status on the 6th day from the start of treatment. At marginal level, one can only suggest a probable prediction of increase in WBC and MON counts, a decrease in CD4+, NK and CD8+perNK, as well as the CD4+/CD8+ ratio. Addition of thymalin to the basic therapy is largely accompanied by the normalization of immunogram parameters. At the same time, it is possible to predict, with excellent rating, an increased number of T-LIM, including CD4+ and B-LIM, and, with good rating, an increase in the total numbers of LIM, as well as CD8+, HLA-CD3+DR+ and NK cells. The data obtained in severe cases of COVID-19 make it possible to predict changes in immune status, and, hence, the course of the disease, at a high degree of probability.
新型冠状病毒感染(COVID-19)后,细胞和体液免疫发生了显著变化。在严重的临床过程中,细胞因子风暴会发展,伴随着促炎细胞因子水平的显著增加,通常与免疫反应的抑制有关。同时,预测免疫状态是一项紧迫的任务,从而可以及时纠正当前的治疗方法。本研究的目的是评估在使用标准治疗或在治疗方案中添加免疫校正胸腺苷时,对COVID-19疾病第6天免疫系统变化的预测能力。对87例新冠肺炎重症患者进行回顾性研究。所有患者分为2组,即(1)对照组接受基础治疗;(2)基础治疗给予胸腺苷(10 mg,每日肌肉注射,连用5天)。COVID-19的严重程度和临床病程评估以及患者的基本治疗方案符合俄罗斯联邦卫生部新冠病毒感染COVID-19的预防、诊断和治疗临时指南的现行版本。在观察的第1天和第6天进行全血计数、免疫图参数和某些类型白细胞比例的计算。统计评价采用专业统计分析语言R (http://cran.r-project.org) 4.1.3版本的脚本进行。采用二值分类法评价血液参数。采用roc分析法对细胞免疫参数的变化进行分类。我们发现COVID-19重症患者在接受基础治疗后,并没有在开始治疗第6天恢复免疫状态。在边际水平上,只能提示WBC和MON计数增加,CD4+、NK和CD8+perNK以及CD4+/CD8+比值降低的可能预测。在基础治疗中加入胸腺苷在很大程度上伴随着免疫图像参数的正常化。同时,可以预测T-LIM(包括CD4+和B-LIM)数量的增加,评分为优;可以预测LIM以及CD8+、HLA-CD3+DR+和NK细胞总数的增加,评分为优。在COVID-19重症病例中获得的数据使人们能够以高概率预测免疫状态的变化,从而预测疾病的病程。
{"title":"Prognosis of immune state following basic therapy and thymalin treatment in patients with severe COVID-19 infection","authors":"B. Kuznik, Yurii N. Smolyakov, K. Shapovalov, P. Tereshkov, V. A. Konnov, N. Chalisova","doi":"10.46235/1028-7221-1209-poi","DOIUrl":"https://doi.org/10.46235/1028-7221-1209-poi","url":null,"abstract":"Significant changes in cellular and humoral immunity are observed in new coronavirus infection (COVID-19). The cytokine storm develops in cases of severe clinical course, being accompanied by significantly increased levels of pro-inflammatory cytokines, often associated with suppression of immune response. At the same time, the prediction of the immune status is an urgent task, thus allowing timely correction of current therapy. The aim of our research was to evaluate predictive capability for the immune system changes on the 6th day of COVID-19 disease when using standard therapy, or with addition of immunocorrector thymalin to the treatment regimen. A retrospective study was conducted in 87 patients with severe COVID-19. All patients were divided into 2 groups, i.e., (1) controls who received basic treatment; (2) basic treatment supplied with thymalin (10 mg, intramuscular injections daily for 5 days). Assessment of severity and clinical course of COVID-19, and basic treatment regimen for the patients corresponded to current version of the interim Guidelines from the Ministry of Health of the Russian Federation Prevention, diagnosis and treatment of a new coronavirus infection COVID-19. Laboratory studies included complete blood counts, immunogram parameters with the calculation of the ratio of certain types of leukocytes were performed on the 1st and 6th days of observation. Statistical evaluation was made using scripts of the specialized statistical analysis language R (http://cran.r-project.org) version 4.1.3. The blood parameters were evaluated using the binary classification method. The changes in parameters of cellular immunity were classified by means of ROC-analysis. \u0000We have found that the basic therapy of severely ill COVID-19 patients was not followed by recovery of immune status on the 6th day from the start of treatment. At marginal level, one can only suggest a probable prediction of increase in WBC and MON counts, a decrease in CD4+, NK and CD8+perNK, as well as the CD4+/CD8+ ratio. Addition of thymalin to the basic therapy is largely accompanied by the normalization of immunogram parameters. At the same time, it is possible to predict, with excellent rating, an increased number of T-LIM, including CD4+ and B-LIM, and, with good rating, an increase in the total numbers of LIM, as well as CD8+, HLA-CD3+DR+ and NK cells. The data obtained in severe cases of COVID-19 make it possible to predict changes in immune status, and, hence, the course of the disease, at a high degree of probability.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83254185","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
Anticytokine activity of Candida spp. and their ability to produce cytokine-like substances 念珠菌的抗细胞因子活性及其产生细胞因子样物质的能力
Pub Date : 2022-12-22 DOI: 10.46235/1028-7221-1150-aao
O. A. Pashinina, Tatyana M. Pashkova, O. L. Kartashova, N. V. Morozova
Bacteria are known both to exhibit anticytokine activity (ACA), i.e., to secrete extracellular compounds which inactivate / neutralize various cytokines, and to produce cytokine-like substances (CPV) released to the culture medium. At the same time, the ability of Candida to secrete such substances has not been previously studied. The purpose of our study was to determine the presence of ACA and the ability to produce CPV in Candida strains isolated from the reproductive tract of apparently healthy pregnant women. The experimental series included 26 clinical strains of Candida spp. isolated from vaginal secretions. Isolation and identification of fungal species was based on morphological and biochemical criteria. ACA against IL-4, IL-6, IL-8, IL-10, IL-17A and TNF were detected following 2-hour co-incubation of fungal suspensions with solutions of the distinct cytokines at a ratio of 1:1. Determination of the cytokine concentrations was carried out by ELISA using the Cytokin kits (St. Petersburg). ACA amounts were defined as the percentage of cytokine inactivation in experimental samples compared to the control expressed as pg/mL. Their ability to produce CPV was expressed as percentage of cytokine production in experimental specimens compared to the controls (pg/mL). The obtained data were subjected to statistical evaluation. ACA of Candida spp. and their ability to produce CPV were revealed for the first time. with appropriate differences established between the studied Candida species, i.e., cultures of C. non-albicans showed ACA more often for the pro-inflammatory cytokines; C. albicans isolates showed more frequent production of the substances, similar to the pro-inflammatory cytokines IL-8, IL-17A, and TNF. Expression of ACA against IL-10 and ability to produce the anti-inflammatory IL-4- and IL-10-like substances were significantly higher in the cultures of C. non-albicans species. The results of these experiments expand our knowledge on the spectrum of Candida biological activities and require further study.
已知细菌既表现出抗细胞因子活性(ACA),即分泌胞外化合物,使各种细胞因子失活/中和,又产生细胞因子样物质(CPV)释放到培养基中。同时,念珠菌分泌这些物质的能力以前还没有被研究过。我们研究的目的是确定ACA的存在以及从表面健康的孕妇生殖道分离的念珠菌菌株产生CPV的能力。实验系列包括从阴道分泌物中分离的26株临床念珠菌。真菌种类的分离和鉴定是基于形态学和生化标准。将真菌悬浮液与不同细胞因子溶液以1:1的比例共孵育2小时,检测ACA对IL-4、IL-6、IL-8、IL-10、IL-17A和TNF的抑制作用。采用细胞因子试剂盒(Cytokin kit, St. Petersburg),采用ELISA法测定细胞因子浓度。ACA量定义为实验样品中细胞因子失活与对照组相比的百分比,以pg/mL表示。与对照组相比,它们产生CPV的能力以实验标本中细胞因子产量的百分比表示(pg/mL)。对所得数据进行统计评价。首次发现念珠菌的ACA及其产生CPV的能力。在所研究的念珠菌种类之间建立了适当的差异,即非白色念珠菌的培养更常显示促炎细胞因子的ACA;分离的白色念珠菌更频繁地产生这些物质,类似于促炎细胞因子IL-8、IL-17A和TNF。在非白色念珠菌中ACA抗IL-10的表达和产生抗炎IL-4和IL-10样物质的能力显著提高。这些实验结果扩大了我们对念珠菌生物活性谱的认识,需要进一步研究。
{"title":"Anticytokine activity of Candida spp. and their ability to produce cytokine-like substances","authors":"O. A. Pashinina, Tatyana M. Pashkova, O. L. Kartashova, N. V. Morozova","doi":"10.46235/1028-7221-1150-aao","DOIUrl":"https://doi.org/10.46235/1028-7221-1150-aao","url":null,"abstract":"Bacteria are known both to exhibit anticytokine activity (ACA), i.e., to secrete extracellular compounds which inactivate / neutralize various cytokines, and to produce cytokine-like substances (CPV) released to the culture medium. At the same time, the ability of Candida to secrete such substances has not been previously studied. The purpose of our study was to determine the presence of ACA and the ability to produce CPV in Candida strains isolated from the reproductive tract of apparently healthy pregnant women. \u0000The experimental series included 26 clinical strains of Candida spp. isolated from vaginal secretions. Isolation and identification of fungal species was based on morphological and biochemical criteria. ACA against IL-4, IL-6, IL-8, IL-10, IL-17A and TNF were detected following 2-hour co-incubation of fungal suspensions with solutions of the distinct cytokines at a ratio of 1:1. Determination of the cytokine concentrations was carried out by ELISA using the Cytokin kits (St. Petersburg). ACA amounts were defined as the percentage of cytokine inactivation in experimental samples compared to the control expressed as pg/mL. Their ability to produce CPV was expressed as percentage of cytokine production in experimental specimens compared to the controls (pg/mL). The obtained data were subjected to statistical evaluation. \u0000ACA of Candida spp. and their ability to produce CPV were revealed for the first time. with appropriate differences established between the studied Candida species, i.e., cultures of C. non-albicans showed ACA more often for the pro-inflammatory cytokines; C. albicans isolates showed more frequent production of the substances, similar to the pro-inflammatory cytokines IL-8, IL-17A, and TNF. Expression of ACA against IL-10 and ability to produce the anti-inflammatory IL-4- and IL-10-like substances were significantly higher in the cultures of C. non-albicans species. \u0000The results of these experiments expand our knowledge on the spectrum of Candida biological activities and require further study.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91268311","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
PD-1 expression on T cell subsets from peripheral blood of patients with allergic diseases 过敏性疾病患者外周血T细胞亚群PD-1的表达
Pub Date : 2022-12-22 DOI: 10.46235/1028-7221-1197-peo
E. Blinova, Victoria A. Galdina, Natalia M. Sukhova, Darja V. Demina
Pathogenesis of allergic diseases is based on the activation of Th2 immune response. T cell response to antigens is known to be regulated by various co-stimulatory and inhibitory signals; inhibitory receptors include PD-1 and Tim-3 molecules. Interaction of the PD-1 receptor with its ligands leads to suppression of activation, proliferation of T cells and production of cytokines by these cells. In chronic bacterial and viral infections, increased expression of PD-1 and Tim-3 on T cells is a marker of cellular exhaustion, since the cytokine production is reduced in cells positive for these inhibitory receptors. Involvement of the co-inhibitory PD-1 receptor into pathogenesis of allergic diseases has not been sufficiently studied, and the data available from the current literature are scarce and contradictory. Therefore, the aim of our study was to evaluate the expression level of co-inhibitory PD-1 and Tim-3 receptors on CD4+ and CD8+T cells, as well as expression of PD-1 on allergen-specific Th2A cells in allergic bronchial asthma (BA) and allergic rhinitis (AR) beyond the pollination season. We used the flow cytometry method to assess immune phenotype of peripheral blood cells from blood donors and patients with allergic diseases, in order to evaluate expression of PD-1 and Tim- 3 markers. The study included 7 patients with allergic asthma, 10 patients with AR beyond the exacerbation phase, and 14 healthy, allergy-free individuals. It was found that the number of CD4+ and CD8+ cells expressing the PD-1 molecule in peripheral blood of patients with BA and AR was within the ranges of healthy individuals. A decrease in CD4+ cells expressing Tim-3 marker was observed only in the group of patients with AR which may be caused both by the absence of pollen allergens and remission of the disease. The content of allergen-specific Th2A cells (CD4+CD45RO+CD27-CRTh2+CD161+) in patients with AR and BA was increased relative to the control group, thus suggesting a pathogenetic significance of this cell population for allergic diseases. However, the level of PD-1 expression on Th2A cells, as well as on the main T cell subpopulations, was comparable to donor values. This finding may suggest that PD-1 may be considered not only a marker of exhaustion as shown for chronic viral infections. Moreover, it also may reflect the activation status of various T cell subpopulations, including allergen-specific Th2A cells in allergic conditions.
过敏性疾病的发病机制是以Th2免疫应答的激活为基础的。已知T细胞对抗原的反应受到各种共刺激和抑制信号的调节;抑制性受体包括PD-1和Tim-3分子。PD-1受体与其配体的相互作用可抑制T细胞的活化、增殖和细胞因子的产生。在慢性细菌和病毒感染中,T细胞上PD-1和Tim-3表达的增加是细胞衰竭的标志,因为在这些抑制受体阳性的细胞中,细胞因子的产生减少。共抑制性PD-1受体参与变应性疾病发病机制的研究尚不充分,目前文献资料匮乏且相互矛盾。因此,我们的研究目的是评估授粉季节后变应性支气管哮喘(BA)和变应性鼻炎(AR)患者CD4+和CD8+T细胞上共抑制PD-1和Tim-3受体的表达水平,以及PD-1在过敏原特异性Th2A细胞上的表达。我们采用流式细胞术方法评估献血者和过敏性疾病患者外周血细胞的免疫表型,以评估PD-1和Tim- 3标志物的表达。该研究包括7名过敏性哮喘患者,10名急性发作期后的AR患者,以及14名健康的无过敏个体。结果发现,BA和AR患者外周血中表达PD-1分子的CD4+和CD8+细胞数量在健康个体范围内。仅在AR患者组中观察到表达Tim-3标记物的CD4+细胞减少,这可能是由于花粉过敏原的缺失和疾病缓解所致。与对照组相比,AR和BA患者的变应原特异性Th2A细胞(CD4+CD45RO+CD27-CRTh2+CD161+)含量增加,提示该细胞群在变应性疾病中具有致病意义。然而,PD-1在Th2A细胞以及主要T细胞亚群上的表达水平与供体值相当。这一发现可能表明,PD-1可能不仅仅是慢性病毒感染的衰竭标志。此外,它也可能反映了各种T细胞亚群的激活状态,包括过敏条件下过敏原特异性Th2A细胞。
{"title":"PD-1 expression on T cell subsets from peripheral blood of patients with allergic diseases","authors":"E. Blinova, Victoria A. Galdina, Natalia M. Sukhova, Darja V. Demina","doi":"10.46235/1028-7221-1197-peo","DOIUrl":"https://doi.org/10.46235/1028-7221-1197-peo","url":null,"abstract":"Pathogenesis of allergic diseases is based on the activation of Th2 immune response. T cell response to antigens is known to be regulated by various co-stimulatory and inhibitory signals; inhibitory receptors include PD-1 and Tim-3 molecules. Interaction of the PD-1 receptor with its ligands leads to suppression of activation, proliferation of T cells and production of cytokines by these cells. In chronic bacterial and viral infections, increased expression of PD-1 and Tim-3 on T cells is a marker of cellular exhaustion, since the cytokine production is reduced in cells positive for these inhibitory receptors. Involvement of the co-inhibitory PD-1 receptor into pathogenesis of allergic diseases has not been sufficiently studied, and the data available from the current literature are scarce and contradictory. Therefore, the aim of our study was to evaluate the expression level of co-inhibitory PD-1 and Tim-3 receptors on CD4+ and CD8+T cells, as well as expression of PD-1 on allergen-specific Th2A cells in allergic bronchial asthma (BA) and allergic rhinitis (AR) beyond the pollination season. We used the flow cytometry method to assess immune phenotype of peripheral blood cells from blood donors and patients with allergic diseases, in order to evaluate expression of PD-1 and Tim- 3 markers. The study included 7 patients with allergic asthma, 10 patients with AR beyond the exacerbation phase, and 14 healthy, allergy-free individuals. It was found that the number of CD4+ and CD8+ cells expressing the PD-1 molecule in peripheral blood of patients with BA and AR was within the ranges of healthy individuals. A decrease in CD4+ cells expressing Tim-3 marker was observed only in the group of patients with AR which may be caused both by the absence of pollen allergens and remission of the disease. The content of allergen-specific Th2A cells (CD4+CD45RO+CD27-CRTh2+CD161+) in patients with AR and BA was increased relative to the control group, thus suggesting a pathogenetic significance of this cell population for allergic diseases. However, the level of PD-1 expression on Th2A cells, as well as on the main T cell subpopulations, was comparable to donor values. This finding may suggest that PD-1 may be considered not only a marker of exhaustion as shown for chronic viral infections. Moreover, it also may reflect the activation status of various T cell subpopulations, including allergen-specific Th2A cells in allergic conditions.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83693323","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
MicroRNA signature of leukocytes in the context of chronic systemic inflammation in vascular dementia 血管性痴呆患者慢性全身性炎症背景下白细胞的MicroRNA特征
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1187-mso
A. Burmistrova, A. Alekseeva, M. Cazaux, Y. Filippova
Chronic low-level inflammation during the aging process is a key risk factor for the activation of resident cells of the brain innate immune system of the (microglia and astrocytes). Such activation leads to the development of neuroinflammation and cognitive impairment which are typical to neurodegenerative diseases such as Alzheimers disease, vascular dementia, Parkinson disease etc. Currently, there is a lack of minimally invasive, affordable methods for diagnosing age-related neurodegenerative diseases and drugs that could slow down or prevent their progression. Hence, a search for new peripheral biomarkers is required, both for diagnostics and monitoring the efficiency of drug therapy. The option of using microRNAs as such biomarkers is under discussion. Our goal was to identify a leukocyte microRNA signature in vascular dementia as compared with healthy aging and reproductive age, in view of inflammation and cognitive deficits. We have examined 54 persons from young to senile age who were classified into the following groups: Vascular dementia, Healthy aging and Reproductive age. Expression of miRNAs known as regulators of communications between the immune and nervous systems (let-7d, let-7g, miR-21, miR-124, miR-146a, miR-155, miR-342-3p) was measured in peripheral blood leukocytes. The decision to study leukocytes was made, since these blood cells are responsible for immune functions, and, especially, cytokine production during aging. Total RNA was isolated by phenol-chloroform technique. The microRNA expression was determined by quantitative polymerase chain reaction with SYBRGreen. The U6 gene of small nuclear DNA was used as a reference housekeeping gene. The differences between groups were determined using the KruskalWallis test with post hoc pairwise comparisons according to ConoverInman. As a result of the study, it was found that the expression of microRNA-21 and microRNA-342 in leukocytes of elderly/senile people, both in healthy aging and in vascular dementia, was increased when compared to the persons in their reproductive age. In the persons with vascular dementia, the expression level of miRNA-124 and miRNA-342 in peripheral blood leukocytes was higher than in healthy aging group. Hence,, microRNA-124 and microRNA-342 may be informative biomarkers for the diagnostics of vascular dementia. However, large-scale studies of their biomarker potential are warranted.
衰老过程中的慢性低水平炎症是激活大脑先天免疫系统(小胶质细胞和星形胶质细胞)的常驻细胞的关键危险因素。这种激活导致神经炎症和认知障碍的发展,这是典型的神经退行性疾病,如阿尔茨海默病、血管性痴呆、帕金森病等。目前,缺乏微创的、可负担得起的方法来诊断与年龄有关的神经退行性疾病,以及可以减缓或阻止其进展的药物。因此,需要寻找新的外周生物标志物,用于诊断和监测药物治疗的效率。使用microrna作为这种生物标志物的选择正在讨论中。考虑到炎症和认知缺陷,我们的目标是鉴定血管性痴呆与健康衰老和生育年龄相比的白细胞microRNA特征。我们检查了54名从青年到老年的人,他们被分为以下三组:血管性痴呆、健康老年和育龄。在外周血白细胞中测量了被称为免疫和神经系统之间通信调节因子的mirna (let-7d, let-7g, miR-21, miR-124, miR-146a, miR-155, miR-342-3p)的表达。研究白细胞的决定是确定的,因为这些血细胞负责免疫功能,特别是在衰老过程中产生细胞因子。用苯酚-氯仿技术分离总RNA。用SYBRGreen定量聚合酶链反应测定microRNA的表达。小核DNA的U6基因作为内参管家基因。根据ConoverInman的说法,使用KruskalWallis检验和事后两两比较来确定组间的差异。研究结果发现,与处于育龄期的人相比,健康衰老和血管性痴呆的老年人白细胞中microRNA-21和microRNA-342的表达均有所增加。血管性痴呆患者外周血白细胞miRNA-124和miRNA-342的表达水平高于健康老年人。因此,microRNA-124和microRNA-342可能是诊断血管性痴呆的信息性生物标志物。然而,对其生物标志物潜力的大规模研究是有必要的。
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引用次数: 1
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Russian Journal of Immunology
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