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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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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.

Autism Spectrum Disorders (ASD) - Searching for the Biological Basis for Behavioral Symptoms and New Therapeutic Targets

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451128 Year: Pages: 178 DOI: 10.3389/978-2-88945-112-8 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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Autism Spectrum Disorder (ASD) is currently diagnosed based on a series of behavioral tests. The challenge for researchers is to try to uncover the biological basis for these typical behaviors in order to improve diagnosis and identify potential targets for treatment. A multidisciplinary approach is necessary in order to move forward. This includes analysis of the current animal models for ASD and their suitability, reviewing immunological, immunogenetic and epigenetic research, reassessing clinical diagnostic tools, and surveying radiological, pathological, and serological records for clues. This volume includes research from some of the leading researchers on ASD. We are hopeful that it will stimulate further dialogue and research in this challenging field.

HLA-G-mediated Immune Tolerance: Past and New Outlooks

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451197 Year: Pages: 92 DOI: 10.3389/978-2-88945-119-7 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2017-07-06 13:27:36
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The non-classical HLA class I molecule HLA-G is different from classical HLA class I molecules because of the low polymorphism in the coding region, the fact that HLA-G primary transcript is alternatively spliced in seven isoforms, and the inhibitory action on immune cells. Although HLA-G is low polymorphic, variants in both promoter and 3’ un-translated region (UTR) of HLA-G locus regulate its expression. In healthy conditions, a basal level of HLA-G gene transcription is observed in most cells and tissues; however, translation into HLA-G protein is restricted to trophoblasts in the placenta, where it participates in promoting tolerance at the fetal-maternal interface. HLA-G is also expressed by thymic epitelial, cornea, mesenchymal stem cells, nail matrix, pancreatic beta cells, erythroid, and endothelial precursors. HLA-G can be neo-expressed in adult tissues in pathological conditions, and its expression has been documented autoimmune disorders, viral infections, and cancer. In the latter setting de novo HLA-G expression is associated with the capability of tumor cells to evade the immune control. In the last decade it has become evident that HLA-G expression on T cells and antigenpresenting cells confers to these cells tolerogenic properties. This Research Topic focused on i) summarizing updated clinical and immunological evidences that HLA-G expression is associate with beneficial or detrimental tolerance, ii) gathering new insights into the mechanisms governing the expression of HLA-G in healthy and pathological conditions, such as pre-eclampsia, and iii) examining the mechanisms underlying HLA-G mediated tolerance.

Major Histocompatibility Complex (MHC) in Health and Disease

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ISBN: 9783039280728 9783039280735 Year: Pages: 375 DOI: 10.3390/books978-3-03928-073-5 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2020-04-07 23:07:08
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The major histocompatibility complex (MHC) is a highly polymorphic and diverse multigene locus in all jawed vertebrate species that has an integral role in adaptive/innate immune systems, transplantation, and infectious and autoimmune diseases. The MHC supra-locus in mammalian vertebrates is usually partitioned into three distinct regions, known as classes I, II, and III, which, to varying extents, can be found conserved in nonmammalian jawed vertebrates, such as bony fish, amphibians, and bird lineages. The MHC gene region is characterized particularly by the expression of class I and class II glycoproteins that bind peptides derived from intracellular or extracellular antigens to circulating T-cells. While this expressed antigenic specificity remains the predominant interest with respect to MHC function and polymorphism in a population, a broader concept has emerged that examines the MHC as a multifunctional polymorphic controller that facilitates and regulates genome diversity with a much greater array of functions and effects than just MHC-restricted antigen recognition. This volume of 19 reprints presented by various experts and collected from the Special Issue of Cells on “MHC in Health and Disease” covers a broad range of topics on the genomic diversity of the MHC regulatory system in various vertebrate species, including MHC class I, II, and III genes; innate and adaptive immunity; neurology; transplantation; haplotypes; infectious and autoimmune diseases; fecundity; conservation; allelic lineages; and evolution. Taken together, these articles demonstrate the immense complexity and diversity of the MHC structure and function within and between different vertebrate species.

Keywords

MHC-I- and MHC-II-dependent inter-individual recognition --- MHC-II-associated sperm-egg recognition --- MHC-I-based mother-fetus recognition --- giant panda --- long-fragment super haplotype --- MHC --- genetic drift --- haplotype --- crested ibis --- founder effect --- bottleneck --- conservation genetics --- selection --- fish --- MHC --- polymorphism --- disease resistance --- quantitative trait loci (QTL) studies --- evolution --- HCP5 --- lncRNA --- MHC --- HLA --- human endogenous retrovirus (HERV) --- cancer --- autoimmune diseases --- competing endogenous RNA (ceRNA) --- human immunodeficiency virus (HIV) --- human papillomavirus (HPV) --- astrogliosis --- PNS/CNS interface --- microglial reaction --- synaptic covering --- ?2m knockout mice --- HLA-B27 --- viral peptides --- computational analysis --- ankylosing spondylitis --- KIR --- KIR–HLA pairs --- ethnic populations in China --- molecular dynamics simulation --- major histocompatibility complex --- antigen --- T-cell receptor --- domain movements --- autoimmunity --- risk genes --- expression --- regulation --- swine leukocyte antigen --- reproductive performance --- production trait --- haplotype --- micro-mini-pigs --- disease association --- haplotype --- HLA polymorphism --- major histocompatibility complex (MHC) --- pedigree --- phase --- protocol --- single nucleotide polymorphism (SNP) --- T1DGC --- type 1 diabetes (T1D) --- BK virus --- polyomavirus --- nephropathy --- human leukocyte antigen-E --- kidney transplantation --- MHC --- ancestral haplotype --- autoimmune disease --- cynomolgus macaque --- Macaca fascicularis --- MHC polymorphism --- experimental medicine --- nonhuman primate models --- DXO --- DOM3Z --- NELF-E --- RD --- SKIV2L --- SKI2W --- STK19 --- RP1 --- NSDK --- RLR --- miR1236 --- SVA --- RNA quality control --- 5??3? RNA decay --- 3??5? mRNA turnover --- antiviral immunity --- interferon ? --- promoter-proximal transcriptional pause --- exosomes --- nuclear kinase --- hepatocellular carcinoma --- Ski complex --- trichohepatoenteric syndrome --- melanoma --- major histocompatibility complex --- MHC --- evolution --- nonclassical --- fish --- MHC genes --- birds --- disease resistance --- orthology --- life history --- gene duplication --- long-read sequencing --- high-throughput sequencing --- concerted evolution --- ecology --- MHC --- major histocompatibility complex --- Old World camels --- camels --- dromedary --- Bactrian camel --- SNP --- n/a

Stem Cell and Biologic Scaffold Engineering

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ISBN: 9783039214976 9783039214983 Year: Pages: 110 DOI: 10.3390/books978-3-03921-498-3 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-12-09 11:49:15
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Tissue engineering and regenerative medicine is a rapidly evolving research field which effectively combines stem cells and biologic scaffolds in order to replace damaged tissues. Biologic scaffolds can be produced through the removal of resident cellular populations using several tissue engineering approaches, such as the decellularization method. Indeed, the decellularization method aims to develop a cell-free biologic scaffold while keeping the extracellular matrix (ECM) intact. Furthermore, biologic scaffolds have been investigated for their in vitro potential for whole organ development. Currently, clinical products composed of decellularized matrices, such as pericardium, urinary bladder, small intestine, heart valves, nerve conduits, trachea, and vessels, are being evaluated for use in human clinical trials. Tissue engineering strategies require the interaction of biologic scaffolds with cellular populations. Among them, stem cells are characterized by unlimited cell division, self-renewal, and differentiation potential, distinguishing themselves as a frontline source for the repopulation of decellularized matrices and scaffolds. Under this scheme, stem cells can be isolated from patients, expanded under good manufacturing practices (GMPs), used for the repopulation of biologic scaffolds and, finally, returned to the patient. The interaction between scaffolds and stem cells is thought to be crucial for their infiltration, adhesion, and differentiation into specific cell types. In addition, biomedical devices such as bioreactors contribute to the uniform repopulation of scaffolds. Until now, remarkable efforts have been made by the scientific society in order to establish the proper repopulation conditions of decellularized matrices and scaffolds. However, parameters such as stem cell number, in vitro cultivation conditions, and specific growth media composition need further evaluation. The ultimate goal is the development of “artificial” tissues similar to native ones, which is achieved by properly combining stem cells and biologic scaffolds and thus bringing them one step closer to personalized medicine. The original research articles and comprehensive reviews in this Special Issue deal with the use of stem cells and biologic scaffolds that utilize state-of-the-art tissue engineering and regenerative medicine approaches.

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