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Antibody Repertoire and Graft Outcome Following Solid Organ Transplantation

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452415 Year: Pages: 176 DOI: 10.3389/978-2-88945-241-5 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2017-10-13 14:57:01
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Abstract

The first real major breakthrough that laid the basis of HLA antibody detection in the field of solid organ transplantation, came with the introduction of the complement dependent cytotoxicity (CDC) test in 1964 by Terasaki and McClelland. Since then, methods for antibody detection have evolved remarkably from conventional cell-based assays to the current advanced solid phase systems on the Luminex platform, with increasing degree of sensitivity and specificity. The latter have been indispensable for more accurate identification of donor specific HLA antibodies in broadly reactive allo antisera, and to guide donor selection and kidney paired exchange programs through virtual crossmatching, in addition to serving as excellent tools for initiating pre-transplant desensitization and post- transplant antibody monitoring. Consensus is evolving on the optimal routine employment of these methods in donor selection strategies along with an understanding of the clinical relevance of antibodies detected by each of them. The immunoassays based on the Luminex platform and flow cytometric beads are however unable to discriminate complement fixing from non-complement fixing HLA antibodies. This is important because the former are considered clinically more pertinent in the peri-transplant period. The C1q assay which is a modification of the solid phase assay based on Luminex single antigen beads, which can be used effectively to monitor high dose IVIG desensitization is essentially a surrogate complement fixing assay, retaining the exquisite sensitivity and specificity of the Luminex platform. Currently, information obtained from these assays is preliminary and much needs to be done to standardize technologies and set a consensus ‘MFI cut off’ for antibody positivity. Besides the overriding influence of anti-HLA antibodies on overall solid organ graft survival, immune response to non-HLA antigens has become a topic of substantial interest in recent years. An ever expanding list of non-HLA antigens has been implicated in graft rejection for various organs, of which the most noted are the Major Histocompatibility Complex class I chain-related molecule A (MICA), Vimentin, Myosin, Angiotensin II type 1 receptor (AT1R), Tubulin and Collagen. MICA is one of the most polymorphic and extensively studied non-HLA antigenic targets especially in renal transplantation. Although there are clear indications of MICA antibodies being associated with adverse graft outcome, to date a definitive consensus on this relationship has not been agreed. Because MICA molecules are not expressed constitutively on immunocompetent cells such as T and B lymphocytes, it is of utmost importance to address the impact of MICA donor specific antibodies (DSA) as compared to those that are non- donor specific (NDSA) on graft outcome. The soluble isoform of MICA molecule (sMICA) that is derived from the proteolytic shedding of membrane bound molecules has the potential to engage the NK-cell activating receptor NKG2D and down-regulate its expression. Consequent to the interaction of NKG2D by sMICA, the receptor ligand complex is endocytosed and degraded and thus suppresses NKG2D mediated lysis of the target by NK cells. Thus interaction between NKG2D and sMICA leads to expansion of immunosuppressive/anergic T cells thereby resulting in suppression of NKG2D mediated host innate immunity. These concept support the possible involvement of an immunosuppressive role for sMICA during allotransplantation as shown recently for heart transplantation. This research topic focuses on the clinical utility of investigating the complete antibody repertoire in solid organ transplantation.

Cell-Free Nucleic Acids

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ISBN: 9783039280742 / 9783039280759 Year: Pages: 248 DOI: 10.3390/books978-3-03928-075-9 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General)
Added to DOAB on : 2020-01-30 16:39:46
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Abstract

The deficits of mammography and the potential of noninvasive diagnostic testing using circulating miRNA profiles are presented in our first review article. Exosomes are important in the transfer of genetic information. The current knowledge on exosome-associated DNAs and on vesicle-associated DNAs and their role in pregnancy-related complications is presented in the next article. The major obstacle is the lack of a standardized technique for the isolation and measurement of exosomes. One review has summarized the latest results on cell-free nucleic acids in inflammatory bowel disease (IBD). Despite the extensive research, the etiology and exact pathogenesis are still unclear, although similarity to the cell-free ribonucleic acids (cfRNAs) observed in other autoimmune diseases seems to be relevant in IBD. Liquid biopsy is a useful tool for the differentiation of leiomyomas and sarcomas in the corpus uteri. One manuscript has collected the most important knowledge of mesenchymal uterine tumors and shows the benefits of noninvasive sampling. Microchimerism has also recently become a hot topic. It is discussed in the context of various forms of transplantation and transplantation-related advanced therapies, the available cell-free nucleic acid (cfNA) markers, and the detection platforms that have been introduced. Ovarian cancer is one of the leading serious malignancies among women, with a high incidence of mortality; the introduction of new noninvasive diagnostic markers could help in its early detection and treatment monitoring. Epigenetic regulation is very important during the development of diseases and drug resistance. Methylation changes are important signs during ovarian cancer development, and it seems that the CDH1 gene is a potential candidate for being a noninvasive biomarker in the diagnosis of ovarian cancer. Preeclampsia is a mysterious disease—despite intensive research, the exact details of its development are unknown. It seems that cell-free nucleic acids could serve as biomarkers for the early detection of this disease. Three research papers deal with the prenatal application of cfDNA. Copy number variants (CNVs) are important subjects for the study of human genome variations, as CNVs can contribute to population diversity and human genetic diseases. These are useful in NIPT as a source of population specific data. The reliability of NIPT depends on the accurate estimation of fetal fraction. Improvement in the success rate of in vitro fertilization (IVF) and embryo transfer (ET) is an important goal. The measurement of embryo-specific small noncoding RNAs in culture media could improve the efficiency of ET.

Keywords

breast cancer --- screening --- liquid biopsy --- omics --- multi-level diagnostics --- individualized patient profile --- miRNA --- mammography --- predictive and preventive approach --- personalized medicine --- cell-free DNA --- exosomes --- extracellular vesicles --- fetal DNA --- preeclampsia --- growth retardation --- gestational diabetes mellitus --- miRNA --- piRNA --- NGS --- RT-PCR --- embryo culture medium --- C19MC microRNA --- expression --- exosomes --- fetal growth restriction --- gestational hypertension --- plasma --- prediction --- preeclampsia --- pregnancy-related complications --- screening --- non-invasive prenatal testing --- statistical models --- z-score --- cell-free nucleic acids --- circulating nucleic acids --- cell-free DNAs --- cell-free RNAs --- exosomes --- inflammatory bowel disease --- neutrophil extracellular traps --- NETosis --- liquid biopsy --- cell-free nucleic acids --- circulating tumor cells --- leiomyomas --- sarcomas --- leiomyosarcomas --- exosomes --- NIPT --- fetal fraction --- statistical methods --- DNA --- maternal serum screening --- fetal cells --- liquid biopsy --- pyrosequencing --- ovarian cancer --- CDH1 --- PTEN --- PAX1 --- RASSF1 --- cfDNA --- cell-free DNA --- nuclease activity --- aging --- obesity --- gender differences --- copy number variants --- next generation sequencing --- non-invasive prenatal testing --- population study --- microchimerism --- solid organ transplantation --- hematopoietic stem cell transplantation --- genetic marker --- single nucleotide polymorphism --- deletion/insertion polymorphism --- ovarian cancer --- circulating miRNA --- blood plasma --- NanoString --- network analysis --- biomarker --- n/a

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