National Repository of Grey Literature 25 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
Complement-binding antibodies in patients after organ transplantation and their clinical relevance
Kovandová, Barbora ; Slavčev, Antonij (advisor) ; Krulová, Magdaléna (referee)
The diagnosis of antibody-mediated rejection after liver transplantation is complicated, due to the fact that the clinical and pathological signs of this life- threatening complication are often overlapping with non-immunological symptoms, like biliary obstruction, ischemia, thrombosis and others. Furthermore, the transplanted liver is to a great extent resistant to this type of rejection. Like in the transplanted kidney and heart, the main pathological factors of graft injury are antibodies directed to the mismatched HLA antigens of the organ donor, i.e. donor- specific antibodies. Besides analysis of HLA specificity of antibodies, research lately has been directed to define whether these antibodies are complement-binding or not. Literature data on this are however up till now limited. Therefore, the aim of this diploma thesis was to study the clinical relevance of complement-binding antibodies against HLA antigens in patients after liver transplantation. Our preliminary results suggest that there might be a correlation between the presence of complement-binding antibodies and the development of antibody-mediated rejection. This finding may play a role for improvement of the prognosis of patients after liver transplantation. Key words HLA, antibodies, C4d, complement, liver transplantation
Regulation of HLA class II genes expression
Zajacová, Marta ; Černá, Marie (advisor) ; Černý, Jan (referee) ; Slavčev, Antonij (referee)
HLA class II genes are known to be highly polymorphic, even in the regulatory non-coding gene regions. Polymorphism in the promoter region potentially forms a strong basis for an uneven allele-specific expression. Even though it is known that the amount of HLA class II molecules on the cell surface has a significant role in shaping immune response, HLA class II expression polymorphism has not yet been thoroughly measured. The thesis aims to shed light into allele-specific mRNA expression and promoter DNA methylation of HLA class II genes. Two studies, each addressing different aspects of the HLA class II allele expression regulation, were conducted. Study A examines the DNA methylation of 10 DQA1 promoter and its effect on the DQA1 mRNA expression. DNA methylation in whole blood cells was determined with bisulfite sequencing and mRNA expression was measured using RT-qPCR. Even though inter-allelic differences in overall methylation were observed (the most methylated alleles were DQA1*02:01 and *04:01), the expected negative correlation between the DQA1 promoter DNA methylation density and the allele expression was not observed. We suggest that the genetic polymorphism in the region (especially region upstream of position -400, which is almost completely methylated in all alleles) may lead to different...
Epigenetic regulation of HLA class II genes in relation to senescence of organism
Říhová, Adéla ; Kotrbová - Kozak, Anna Katarzyna (advisor) ; Slavčev, Antonij (referee)
Introduction: Glycoproteins of the major histocompatibility complex (MHC) are an irreplaceable part of immune response regulation and immune homeostasis maintenance. The regulation of the expression plays an important role in adaptive immune response. Recently, DNA methylation in regulatory areas, crucial for DNA availability to transcription factors, is one of the most researched mechanisms of this type of regulation. The DNA methylation is, among others, related to the aging processes. Increased predisposition age-related immunosenescence in higher age could result from the changes in methylation status of regulatory areas of MHC class II genes. Aims: The aim of this thesis is to analyze the methylation status of regulatory areas of DQB1 gene and to compare the differences between generations and specific alleles. The differences in the levels of DQB1 gene mRNA transcription between generations and specific alleles is also compared. Methods: Both DNA and RNA were isolated from blood samples obtained from donors of three different age groups. DNA was genotypized and modified by bisulfite conversion. The regulatory areas of DQB1 genes were then amplified and subcloned into bacteria. The positive clones were selected and subjected to DNA methylation analysis. RNA was reverse transcribed into cDNA...
Role of BAFF cytokine in transplantation reactons
Sekerková, Zuzana ; Slavčev, Antonij (advisor) ; Krulová, Magdaléna (referee)
Current immunogenetic tests before organ transplantation include HLA typing and detection of HLA-specific antibodies. However, these tests do not provide information about the B cells participating in the humoral response against the transplanted organ. BAFF (B activating factor) plays an important role in the proliferation, maturation and differentiation of B cells. A soluble form of the cytokine arises after splicing the membrane form of BAFF. The soluble cytokine binds to three types of receptors - TACI, BCMA and BCMA. Some recent studies suggest that BAFF could serve as a marker or predictor of antibody-mediated (humoral) rejection in kidney transplant recipients. Our study consists of two parts. The first part is focused on the detection of soluble BAFF levels in patients after renal transplantation. The aim of our study was therefore to correlate levels of soluble BAFF cytokine in patients before and after transplantation with the clinical course and incidence of rejection after transplantation. The study included 92 kidney recipients. Humoral rejection was diagnosed on the basis of a positive finding of C4d deposits in peritubular capillaries (imunoflorescenční detection), and the presence of donor- specific antibodies. BAFF levels were determined using Xmap methodology by the Luminex method...
The role of B cells in transplantation reactions
Brožová, Jitka ; Slavčev, Antonij (advisor) ; Stříž, Ilja (referee)
Kidney transplantation is the best treatment for patients with end-stage renal failure. The main problem of kidney transplantation is however the development of a cellular and antibody-mediated (humoral) rejection. During the last decade, thanks to the advanced immunosuppression, prognosis of survival and function of transplanted organs has significantly improved. Nevertheless, humoral rejection remains very serious obstacle in high-risk patients, because it can permanently damage the graft. Therefore, before transplantation it is necessary to stratify patients into high and low risk groups for development of antibody-mediated rejection. Current immunogenetic tests performed before transplantation include, in addition to HLA typing, detection of panel-reactive antibodies. However, this test does not provide information about B cells which participate in the humoral response of the kidney recipient. Therefore, in the presented thesis we studied B cell reactivity and its regulation in transplanted patients. In this retrospective analysis we measured levels of the B cell activating factor, a cytokine regulating the function of B lymphocytes (BAFF). Current reports suggest that BAFF could serve as a marker of humoral rejection. Furthermore, we focused on B lymphocytes and their capacity to produce...
HLA neshody u pacientů po opakované transplantaci ledviny a incidence akutní buněčné a protilátkami zprostředkované rejekce.
Karasová, Alexandra ; Slavčev, Antonij (advisor) ; Ambrůzová, Zuzana (referee)
Kidney transplantation is the most appropriate treatment for end-stage kidney failure. The risk of graft failure in retransplanted patients is generally higher than in first-transplant patients due to immunological and non-immunological reasons. An important risk factor to consider for retransplant patients is their sensitization, i.e. the presence of antibodies directed to HLA antigens of previous donor(s). For that reason, a project called Forbidden (Non-acceptable) Antigens was launched by IKEM with the aim of reducing the incidence of acute cellular and antibody-mediated rejection in retransplant patients. Work on the project was carried out between the years 2011-2013. Forbidden antigens were defined as mismatched HLA antigens of previous kidney donor(s) against which patients waiting for retransplantation produced antibodies. The aim of this diploma thesis is to evaluate whether the incidence of rejection is lower in patients with forbidden HLA antigens in comparison with a control cohort, where no forbidden antigens are defined. 234 patients (162 males and 72 females) were included in the study. Almost all tested patients were producing HLA antibodies (90.2%) and forbidden antigens were determined in 71.4% of patients. In a control group of 267 patients waiting for their first transplantation, the...
Cytokine polarisation in immunopathological disorders
Durilová, Marianna ; Štechová, Kateřina (advisor) ; Tučková, Ludmila (referee) ; Slavčev, Antonij (referee)
6 Abstract Cytokines as primary modulators of immune system cells play a key role in their development, maintenance and activity of each cell population. Cytokine profile of peripheral blood mononuclear cells thus reflects the immunopathological events involved in pathogenesis of the disease. Focus of my thesis was cytokine dysbalance in several immunopathological disorders (type 1 diabetes mellitus, autoimmune thyroiditis, allergic colitis) with the aim to find distinctive cytokine profile of each disorder and to point out common features and differences in these disorders. Protein array and enzyme-linked immunosorbent assay (ELISA) method were used for analysis of cytokines in breast milk and cytokines produced in vitro by peripheral and cord blood mononuclear cells spontaneously and after stimulation by autoantigens. First immunological disorder to study was type 1 diabetes mellitus (T1D), where patients with T1D were studied (n = 10) as well as their first degree relatives (n = 9), with particular group of neonates whose one parent suffered from T1D (n = 52). In patients with T1D prediabetic phase was dominated by spontaneous and postimulatory production of Th1- associated cytokines (IFN-γ, TNF-β) which dropped at the time of T1D manifestation and remained suppressed for at least two following years....
ELISpot methodology and prediction of acute rejection after renal transplantation.
Rybáková, Kateřina ; Slavčev, Antonij (advisor) ; Mrázek, František (referee)
Transplantation is the best therapeutic solution for patients with chronic renal failure. Due to the great advances in immunosuppressive therapy in the last decades, graft and patient survival have improved significantly. On the other hand, immunosuppressive therapy has serious side effects - too strong immunosuppression may lead to infection or malignancies, conversely insufficient immunosuppression may lead to graft rejection. Due to the grave consequences of acute rejection, the main goal of cooperation of clinicians and transplant immunologists is to stratify patients into groups with low, moderate and high risk of rejection based on the evaluation of various immunologic risk factors. There are reports in the literature that the numbers (frequencies) of interferon gamma (IFNγ) producing cells before transplantation may be helpful to identify patients with high risk of acute cellular rejection and to predict long-term survival of the graft. In this retrospective study we determined the pre-transplant frequencies of activated donor specific T lymphocytes producing IFNγ after short stimulation (24 hrs) by ELISpot (Enzyme-linked immunosorbent spot assay). The results were correlated with the incidence of acute cellular (ACR) and antibody-mediated (AMR) rejection and with other risk factors. In our...

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