Immunological factor development of external genital endometriosis

External genital endometriosis (EGE) is one of the common gynecological diseases of women of reproductive age with a relapsing, progressive course that worsens the quality of life of patients due to pain, emotional imbalance, fear of relapse and possible surgical intervention. Currently, endometriosis is recognized as one of the most common diseases associated with infertility. Thus, among fertile women with preserved childbearing function, the disease is generally diagnosed in approximately 6-7%, while among patients suffering from infertility, its frequency can reach 20-48%.However, the causes that determine reproductive dysfunction in patients with EGE are not well understood. Much attention is currently paid to the role of immunity in the formation of endometriosis. Patients with EGE show changes in both local immunity factors and immunological components of circulating blood.Purpose of the study: the study of factors of innate and adaptive immunity in patients of reproductive age with external genital endometriosis (EGE).The study included 71 patients with various stages of external genital endometriosis, the control group included 24 patients without endometriosis. Determination of the population composition of peripheral blood lymphocytes, the level of monocytes expressing TLR, activation markers, was carried out by laser flow cytometry — Immunotex (France), Caltag (USA), FITC (fluorescein isothiocynate) — labeled CD3, CD4, CD8, CD16, CD19, HLA-DR, CD282, CD284 and PE (phycoerythrin) - labeled with CD25, CD69, CD95, CD107a, CD14.External genital endometriosis is characterized by: at stages I-II of the disease - a violation of the early stages of the innate immune response (an increase in the number of monocytes expressing TLR-4, a violation of the activation and differentiation processes of immunocompetent cells, which is reflected in a decrease in the expression of CD16, CD8, CD16+HLA-DR+, CD16+CD107a+, CD8+CD107a+, at III-IV stages of the disease, there is a decrease in the level of CD16 and activation markers CD69, HLA-DR, CD107a on their surface, which is combined with a decrease in the expression of CD8, CD16, HLADR and CD107a on their surface. CD95+ and CD8+CD95+ were found at various stages of EGE.The results obtained allow us to understand the features of the functioning of innate and adaptive immunity at various stages of external genital endometriosis, and the studied immunological parameters can be used as diagnostic criteria for the formation of various stages of EGE. These data can serve as a theoretical basis for further identification of markers of EGE progression, as well as the mechanisms underlying immune inflammation

FACTORS OF CONGENITAL AND ADAPTIVE IMMUNITY IN THE PATHOGENESIS OF INTRAUTERINE GENERATED CYTOMEGALOVIRUS INFECTION

Subject: to assess a role of factors of innate and adaptive immunity in the development of intrauterine generalized cytomegalovirus infection.The study included 47 newborns with congenital generalized cytomegalovirus infection comprising group I. Based on the data of clinical and laboratory examination, all newborns studied were divided into two subgroups. Subgroup 1.1 (29 subjects) consisted of newborns with severe CMVI and subgroup 1.2 (18 subjects) – newborns with moderate CMVI. The control group included 26 newborns without herpesvirus infection.Determination of the number of monocytes expressing Toll receptors (TLR) was performed by laser flow cytometry (Beckman Coulter) using Beckman Coulter, HyCultBiotechnology reagents: FITC-CD282+, CD284+, CD286+, and PE-CD14+. The newborn serum concentration of IFNγ, IFNα, IL-6, IL-8 was determined by ELISA using BenderMedsistems test systems.Intrauterine generalized CMVI with complete clinical symptoms in newborns was characterized by a decrease in the number of monocytes expressing TLR-2 and TLR-6, which was associated with a decrease in the level of IFNα, IFNγ, an increase in the level of IL-6, IL-8 and MCP-1. The subgroup with incomplete clinical symptoms CMVI was characterized by a decrease in the level of IFNα, in combination with an increase in the level of IL-6. The identified immune disorders lead to a reduction in the antiviral immune response and determine the severity of the disease in prenatally infected newborns

Features of the cytokine profile in adolescents with microvascular complications of type 1 diabetes mellitus

Despite advances of modern medical science, the consequences associated with management of complications in type 1 diabetes mellitus (DM1) in children and adolescents represent a serious problem. Common development of microvascular diabetic complications (retinopathy, neuropathy, kidney damage) still remains a sufficient obstacle for achieving high quality of life and social adaptation in the young patients, thus promoting studies of immune mechanisms involved in genesis of microvasculature damage under the conditions of dysmetabolic abnormalities associated with DM1. Our goal was to assess the role of altered cytokine balance in blood serum in development of microangiopathies in adolescents with DM1.140 adolescent patients with type 1 diabetes aged 14-18 years were examined being divided in 2 groups: group I included the patients with glycated hemoglobin (HbA1c) level of > 9.0% (n = 65), and group II which included adolescents with HbA1C level of ≤ 9.0% (n = 75). Each group was divided into subgroups: Ia (n = 50) and IIa (n = 38) included adolescents with diabetic retinopathy, nephropathy or neuropathy, whereas groups Ib (n = 15) and IIb (n = 37) were without microvascular complications. The control group consisted of 36 adolescents with normal body weight, without carbohydrate metabolic disorders, and family history of diabetes mellitus. Determination of TNFα, IL-1β, VCAM-1, fractalkine levels in blood serum was performed by enzyme immunoassay using test systems “RayBiotech” (USA), “BIOSCIENCE” (USA).Development of microangiopathies in adolescents with different glycemic control is associated with increased serum concentration of the factors involved in neoangiogenesis and vascular wall remodeling, i.e., TNFα, IL-1β, VCAM-1, compared with control group (p < 0.05), and a statistically significant decrease in fractalkine level in adolescent patients with either complicated, or uncomplicated DM1. The study allowed us to suggest that occurrence of microvascular complications in adolescents with DM1 is associated with impaired immune response tending for altered cytokine balance towards Th1 type, enhanced intercellular interactions, imbalance of bioregulatory molecules, contributing to development of inflammatory immunoregulatory state. The revealed patterns of laboratory markers, along with assessment of metabolic indices, will enable personalized approaches to early diagnostics of microvascular complications in adolescents with DM1 and prevent their further progression

Клинико-диагностическая значимость определения цитокинового статуса у детей грудного возраста с хроническим течением цитомегаловирусной инфекциии на фоне гипоксически-ишемического поражения ЦНС

Objective: based on the production of cytokines, to identify the immunological features of the chronic course of cytomegalovirus infection in children of the first year of life against the background of hypoxic-ischemic CNS damage.Research methods:108 newborns with cytomegalovirus infection occurring against the background of perinatal hypoxic-ischemic lesions of the central unequal system were examined. All observed patients immediately after the diagnosis of cytomegalovirus infection underwent an immunological examination, including the determination of the levels of interferon-alpha (IFN-α) and interferon-gamma (IFN-γ), the level of interleukins — 2 and 4 (IL -2 and IL-4) necrosis factor human alpha tumors (TNF-α in blood serum was determined by enzyme immunoassay using a set of reagents ProCon IF2 plus, ProCon Ifgamma, ProCon TNFα (Protein contour LLC, Russia, St. Petersburg). At 1 and 6 months of life .The observation groups consisted of 78 children (72.2%) with an acute course of the disease (Group 1) and 30 children (27.3%) with a chronic course (Group 2). The control group consisted of 15 newborns without herpes virus infection.Results. Of the totality of the studied cytokines, statistically significant for the chronic course of cytomegalovirus infection in children of the first year of life against the background of hypoxic-ischemic CNS damage were found: IL-2, IFN-γ. It was found that in children with a persistent low level of IFN-γ and an increased level of IL-4 in the blood serum at the age of 6 months, there was a chronic course of cytomegalovirus infection against the background of perinatal hypoxic-ischemic CNS damage.A decrease in IFN-γ production indicates a congenital or acquired deficiency of the interferon system and can be considered as an indication for long-term interferon replacement therapy.Цель исследования: изучить особенности цитокинового статуса при хроническом течении цитомегаловирусной инфекции, у детей первого года жизни на фоне гипоксически-ишемического поражения ЦНС.Методы исследования: обследовано 108 новорожденных с цитомегаловирусной инфекцией, протекавшей на фоне перинатального гипоксически-ишемического поражения центральной неравной системы. Всем наблюдавшимся пациентам сразу после постановки диагноза цитомегаловирусная инфекция проводили иммунологическое обследование, включающее определение уровней интерферона-альфа (ИФН-α) и интерферона-гамма (ИФН-γ) уровень интерлейкинов — 2 и 4 (ИЛ-2 и ИЛ-4), фактора некроза опухолей альфа человека (ФНО-α) в сыворотке крови определяли методом иммуноферментного анализа с помощью набора реагентов ProConIF2 plus, ProConIfgamma, ProConTNFα (ООО «Протеиновый контур», Россия, г. Санкт-Петербург) в возрасте 1 и 6 месяцев жизни. Группы наблюдения составили 78 детей (72,2%) с острым течением заболевания (1 группа) и 30 детей (27,3%) с хроническим течением (2 группа). Контрольную группу составили 15 новорожденных без герпесвирусной инфекции.Результаты. Из всей совокупности изучаемых цитокинов были обнаружены статистически значимые для хронического течения цитомегаловирусной инфекции (ЦМВИ) у детей первого года жизни на фоне гипоксически-ишемического поражения ЦНС: ИЛ- 2 и ИФН-γ. Выявлено, что у детей с сохраняющимся пониженным уровнем ИФН-γ и повышенным уровнем ИЛ-4 в сыворотке крови в возрасте 6 месяцев имело место хроническое течение цитомегаловирусной инфекции на фоне перинатального гипоксически-ишемического поражения ЦНС.Снижение продукции ИФН-γ, свидетельствует о врождённом или приобретённом дефиците системы интерферонов и может рассматриваться как показание для длительной заместительной терапии интерферонами

Прогнозирование частых острых респираторных инфекций на первом году жизни у детей с церебральной ишемией, перенесших цитомегаловирусную инфекцию в периоде новорожденности

Objective: to develop prognostic criteria for frequent respiratory diseases in the first year of life in children with cerebral ischemia who had a cytomegalovirus infection in the neonatal period. Research methods: 73 children of the first year of life with cerebral ischemia, who underwent cytomegalovirus infection in the neonatal period, were deployed. All observed patients at the age of three months underwent a study of the population composition of peripheral blood T-lymphocytes using flow cytometry for the expression of membrane markers, taking into account the results on a Beckman Coulter Epics XL II laser flow cytometer. Typing of lymphocytes was carried out using monoclonal antibodies to differentiation clusters CD3+, CD3+CD69+, CD3+CD71+, CD3+CD95+ from Immunotech (France). The observation groups consisted of 30 children (41.1%) with frequent acute respiratory infections (4—5 episodes per year) in the first year of life and 43 people (58.9%) — children with no acute respiratory infection’sepisodes in the first-year life. Results. From the set of studied T-lymphocytes, statistically significant for the prognosis of frequent acute respiratory infections in the first year of life in children with cerebral ischemia who underwent cytomegalovirus infection in the neonatal period were found: CD3+ CD71+, CD3+ CD95+. It was revealed that in children with a reduced level of CD3+ CD71+ and an increased level of CD3+ CD95+ in blood serum at the age of 3 months, frequent acute respiratory infections occurred in the first year of life.Цель исследования: разработать прогностические критерии частых острых респираторных инфекций на первом году жизни у детей с церебральной ишемией, перенесших цитомегаловирусную инфекцию в периоде новорожденности. Материалы и методы: обследовано 73 ребенка первого года жизни с церебральной ишемией, перенесших цитомегаловирусную инфекцию в периоде новорожденности. Всем наблюдавшимся пациентам в возрасте трех месяцев проведено исследование популяционного состава Т-лимфоцитов периферической крови с помощью проточной цитофлюориметрии по экспрессии мембранных маркеров с учетом результатов на проточном лазерном цитофлюориметре Beckman Coulter Epics XL II. Типирование лимфоцитов проводили с помощью моноклональных антител к кластерам дифференцировки СD3+, CD3+ CD69+, CD3+ CD71+, CD3+ CD95+ фирмы Immunotech (Франция). Группы наблюдения составили 30 детей (41,1%) с частыми острыми респираторным инфекциями (ОРИ) (4—5 эпизодов в год) на первом году жизни и 43 человека (58,9%) — дети с отсутствием эпизодов ОРИ на первом году жизни (контрольная группа). Результаты. Из совокупности изучаемых Т-лимфоцитов были обнаружены статистически значимые для прогноза частых острых респираторных инфекций на первом году жизни у детей с церебральной ишемией, перенесших цитомегаловирусную инфекцию в периоде новорожденности: CD3+ CD71+, CD3+ CD95+. Выявлено, что у детей с пониженным уровнем CD3+ CD71+ и повышенным уровнем CD3+ CD95+ в сыворотке крови в возрасте 3-х месяцев жизни имели место частые острые респираторные инфекции на первом году жизни