|
|
Significance of the major histocompatibility complex for organ transplantation
Ilina, Liudmila ; Slavčev, Antonij (advisor) ; Grobárová, Valéria (referee)
The major histocompatibility system is a region in the human genome located on chromosome 6. HLA genes encode polymorphic cell-surface glycoproteins which are primarily responsible for presentation of self and non-self antigens to T cells. When the T lymphocyte recognizes the MHC-peptide complex as foreign, it activates effector components of the innate and adaptive immune system. Therefore, mismatched HLA antigens can lead to a strong immune response against the donor's tissue. HLA laboratories support transplant programs by evaluation the HLA matching between patients and their potential donors and, based on these data, assist in the evaluation of the risk of rejection and eventual immunological complications after transplantation. The aim of this thesis is to describe the significance of the major histocompatibility complex for the occurrence of cellular and antibody-mediated rejection after solid organ transplantation and discuss the relationship between the degree of HLA matching and graft survival outcomes. Key words HLA, organ transplantation, rejection
|
|
|
Role of antibodies against HLA and non HLA antigens for organ transplantation.
Svobodová, Eva
Rejection is a significant complication after transplantation and one of the main reasons for loss of graft function. It is triggered by the response of the organ recipient's immune system based on the recognition of mismatched HLA (Human Leukocyte Antigens) and non-HLA antigens of the donor. All components of the immune system participate in this process, and according to the predominance of individual reactions, rejection can be divided into T cell-mediated rejection (TCMR) and antibody-mediated rejection (AMR). Rejection can develop immediately after transplantation in an acute form, or as a chronic form during several to tens of years after transplantation. The diagnosis of rejection is determined according to the clinical status, laboratory tests (including the detection of donor-specific antibodies, DSA) and histological findings in biopsies. The knowledge of validated gene expressions from the molecular microscope (MMDX) and other diagnostic tests has been recently applied. Individual phenotypes of rejection are evaluated and revised according to the international pathological classification. This work focuses on the analysis of immunological factors in relation to T-cell and antibody- mediated rejection after organ transplantation. The thesis deals with the determination of DSA in relation...
|
|
|
Role of antibodies against HLA and non HLA antigens for organ transplantation.
Svobodová, Eva ; Slavčev, Antonij (advisor) ; Mrázek, František (referee) ; Černá, Marie (referee)
Rejection is a significant complication after transplantation and one of the main reasons for loss of graft function. It is triggered by the response of the organ recipient's immune system based on the recognition of mismatched HLA (Human Leukocyte Antigens) and non-HLA antigens of the donor. All components of the immune system participate in this process, and according to the predominance of individual reactions, rejection can be divided into T cell-mediated rejection (TCMR) and antibody-mediated rejection (AMR). Rejection can develop immediately after transplantation in an acute form, or as a chronic form during several to tens of years after transplantation. The diagnosis of rejection is determined according to the clinical status, laboratory tests (including the detection of donor-specific antibodies, DSA) and histological findings in biopsies. The knowledge of validated gene expressions from the molecular microscope (MMDX) and other diagnostic tests has been recently applied. Individual phenotypes of rejection are evaluated and revised according to the international pathological classification. This work focuses on the analysis of immunological factors in relation to T-cell and antibody- mediated rejection after organ transplantation. The thesis deals with the determination of DSA in relation...
|
|
|
Significance of the major histocompatibility complex for hemopoietic stem cell transplantation
Graman, Vojtěch ; Slavčev, Antonij (advisor) ; Dobeš, Jan (referee)
The genes of the major histocompatibility complex are located on the short arm of chromosome 6 and encode surface glycoproteins (HLA glycoproteins), which ensure the presentation of self and foreign peptides on the cell surface. These glycoproteins are subsequently recognized by T-lymphocytes and by other cells of the immune system. When the HLA-peptide complex is recognized as foreign, T-lymphocytes and other components of the immune system are activated, and the foreign cell is destroyed. Therefore, in hematopoietic stem cell transplantation (HSCT), HLA incompatibility between donor and recipient causes a strong immune response against the transplanted cells, and is therefore a major criterion in selecting suitable stem cell donors. This work briefly summarizes the current knowledge about the structure and function of HLA class I and class II antigens. The work focuses on HLA typing techniques to help understand the HLA system, which include serological typing methods, as well as modern molecular typing methods based on PCR and next-generation sequencing, and their relevance for HSCT. We also focus on HSCT processes and preparatory therapy, but the main emphasis is on the importance of HLA incompatibilities between stem cell recipients and donors and their effect on HSCT outcome.
|
|
|
Study of HLA antigens and KIR genes in a donors and recipients of bone marrow
Kroulíková, Zuzana ; Vraná, Milena (advisor) ; Froňková, Eva (referee)
HLA and KIR genes are highly polymorphic regions within the human genome. Protein products of these genes play a critical role in hematopoietic stem cell transplantation. Genetic HLA match is a major barrier to engraftment and influences the outcome of this therapy. Therefore it is necessary to genotype donors and recipients selected for hematopoietic stem cell transplantation. Today HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 genes are tested by modifications of polymerase chain reaction or by sequence-based typing methods on the level of high- or low-resolution. Donors registered in bone marrow registries are selected on the basis of a 10/10 match. Donors KIR genotype leads to a better outcome, to relapse-free survival and overall survival in treatment of patients with acute myeloid leukemia. A better protection against relapse is achieved by Cen-B/B donor haplotype. Therefore KIR typing by polymerase chain reaction is used and the genotype is compared with the IMGT/KIR database by an online B- content calculator. Donors are divided in groups according to their genotype and their influence on the success of treatment for acute myeloid leukemia. The study of polymorphic systems and the development of genotyping donors and recipients significantly improve the outcome of hematopoietic stem cell...
|
|
|
Epitopes of HLA antigens and their relevance for organ transplantation program
Šutta, Adrián ; Slavčev, Antonij (advisor) ; Hájková, Michaela (referee)
and Key words This diploma thesis is focused on assessing the potential benefit of HLA epitopes for the prediction of de novo antibody production at kidney transplant recipients. The topic and patient selection criteria were selected in accordance with the 18th International HLA and Immunogenetics workshop (IHIWS), which is taking place in May 2022 in the Netherlands, where our data will also be contributed. Our aims were to compare HLA antigens mismatches (counted as total number of mismatched alleles) defined on the high-resolution level by NGS sequencing, HLA eplets mismatches defined by HLA matchmaker, and amino acid mismatches defined by HLA EMMA in their capacity to predict de novo antibody production and compare these results to other works by different authors from this field. We have identified N= 28 patients who developed de novo antibodies and N= 19 who didn't develop de novo antibodies in 5 years follow up their transplant. These two cohorts were compared based on all three approaches and correlation between number of mismatches and number of patients with de novo antibodies were made using ROC curves. Superiority of eplet mismatches over HLA antigen mismatches (total number of mismatched alleles) defined on high resolution was not detected. The HLA epitopes identified by the HLA...
|
|
|
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
|
|
|
Study of HLA antigens and KIR genes in a donors and recipients of bone marrow
Kroulíková, Zuzana ; Vraná, Milena (advisor) ; Froňková, Eva (referee)
HLA and KIR genes are highly polymorphic regions within the human genome. Protein products of these genes play a critical role in hematopoietic stem cell transplantation. Genetic HLA match is a major barrier to engraftment and influences the outcome of this therapy. Therefore it is necessary to genotype donors and recipients selected for hematopoietic stem cell transplantation. Today HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 genes are tested by modifications of polymerase chain reaction or by sequence-based typing methods on the level of high- or low-resolution. Donors registered in bone marrow registries are selected on the basis of a 10/10 match. Donors KIR genotype leads to a better outcome, to relapse-free survival and overall survival in treatment of patients with acute myeloid leukemia. A better protection against relapse is achieved by Cen-B/B donor haplotype. Therefore KIR typing by polymerase chain reaction is used and the genotype is compared with the IMGT/KIR database by an online B- content calculator. Donors are divided in groups according to their genotype and their influence on the success of treatment for acute myeloid leukemia. The study of polymorphic systems and the development of genotyping donors and recipients significantly improve the outcome of hematopoietic stem cell...
|
|
|
Genetic and molecular factors influencing the outcome of solid organ transplantation
Pavlova, Yelena ; Slavčev, Antonij (advisor) ; Kalina, Tomáš (referee) ; Mrázek, František (referee)
Since its beginning, graft rejection remains the key problem of solid organ transplantation. This reaction of the recipient's immune system against mismatched antigens of the transplanted organ causes graft damage and consequently loss of its function. Rejection involves cellular (lymphocyte mediated) and humoral (antibody mediated) mechanisms. Among the genetic factors which may have a prognostic value in rejection risk evaluation are the Human Leukocyte Antigens (HLA) genotype, the Killer Immunoglobuline-like Receptor (KIR) gene repertoir, cytokine and other gene polymorphisms. These factors could be screened for before transplantation to find the best possible combination of genetic characteristics of the donor and recipient and to reveal patients with "risky" genotypes, who may need more intensive immunosuppression and more careful post-transplant follow-up. Molecular factors, such as HLA and non-HLA antibodies, soluble CD30 molecule (sCD30), Hepatocyte Growth Factor (HGF) and other cytokines, measured before and/or after transplantation in the recipient's blood may be helpful for rejection risk estimation and may also be used as post-transplant rejection onset markers. In our study, we focused on some of the above mentioned factors. We found that ethnicity plays a significant role in the...
|
|
| |
guest ::
