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Purpose: The main objective of static cold storage is to reduce cellular metabolic demands to extend the period of ischaemia prior to transplantation. Hypothermia does not halt metabolism and the absence of oxygen causes a cellular shift toward anaerobic respiratory pathways. There is emerging evidence that the introduction of oxygenation during organ preservation may help ameliorate the degree of ischaemia reperfusion injury and improve post-transplantation outcomes. This review aims to appraise and summarise all published literature that utilises oxygenation to improve kidney preservation for purposes of transplantation. Methods: We performed a scoping review of the literature using the bibliographic databases Embase and MEDLINE. The final date for searches was 20 March 2021. All research studies included were those that reported oxygen delivery during kidney preservation as well as providing a description of the oxygenation technique. Results: 17 human and 48 animal studies met the inclusion criteria. The oxygen delivery methods investigated included hypothermic oxygenated machine perfusion (HOPE), oxygen carriers, two-layer method, venous systemic persufflation, hyperbaric oxygenation, normothermic machine perfusion and sub-normothermic machine perfusion. The COMPARE trial was the only study carried out with the most methodological robustness being a randomised, double blind, controlled, phase III trial that investigated the efficacy of HOPE versus HMP. Conclusion: A variety of studies reflect the evolution of oxygenation with useful lessons and encouraging outcomes. The first in human studies investigating HOPE and oxygen carriers are most robustly investigated strategies for oxygenation during kidney preservation and are, therefore, the best clinical references. [ABSTRACT FROM AUTHOR]

The olive baboon represents an important model system to study various aspects of human biology and health, including the origin and diversity of the major histocompatibility complex. After screening of a group of related animals for polymorphisms associated with a well-defined microsatellite marker, subsequent MHC class I typing of a selected population of 24 animals was performed on two distinct next-generation sequencing (NGS) platforms. A substantial number of 21 A and 80 B transcripts were discovered, about half of which had not been previously reported. Per animal, from one to four highly transcribed A alleles (majors) were observed, in addition to ones characterised by low transcripion levels (minors), such as members of the A*14 lineage. Furthermore, in one animal, up to 13 B alleles with differential transcription level profiles may be present. Based on segregation profiles, 16 Paan-AB haplotypes were defined. A haplotype encodes in general one or two major A and three to seven B transcripts, respectively. A further peculiarity is the presence of at least one copy of a B*02 lineage on nearly every haplotype, which indicates that B*02 represents a separate locus with probably a specialistic function. Haplotypes appear to be generated by recombination-like events, and the breakpoints map not only between the A and B regions but also within the B region itself. Therefore, the genetic makeup of the olive baboon MHC class I region appears to have been subject to a similar or even more complex expansion process than the one documented for macaque species. [ABSTRACT FROM AUTHOR]

Gene products of the major histocompatibility complex (MHC) of human and non-human primates play a crucial role in adaptive immunity, and most of the relevant genes not only show a high degree of variability (polymorphism) but also copy number variation (CNV) is observed. Due to this diversity, MHC proteins influence the capability of individuals to cope with various pathogens. MHC and/or MHC-linked gene products such as odorant receptor genes are thought to influence mate choice and reproductive success. Therefore, MHC typing of wild and captive primate populations is considered to be useful in conservation biology, which is, however, often hampered by the need of invasive and time-consuming methods. All intact Mhc-DRB genes in primates appear to possess a complex and highly divergent microsatellite, DRB-STR. A panel of 154 pedigreed olive baboons ( Papio anubis) was examined for their DRB content by DRB-STR analysis of genomic DNA. Using the same methodology on DNA of feces samples, DRB variability of a silvery gibbon population ( Hylobates moloch) ( N = 24), an endangered species, could successfully be studied. In both species, length determination of the DRB-STR resulted in the definition of unique genotyping patterns that appeared to be specific for a certain chromosome. Moreover, the different STR lengths were shown to segregate with the allelic variation of the respective gene. The results obtained expand data gained previously on DRB-STR typing in macaques, great apes, and humans and strengthen the conclusion that this protocol is applicable in molecular ecology, conservation biology, and colony management, especially of endangered primate species. [ABSTRACT FROM AUTHOR]

Bortezomib has appeared recently as a potential active treatment for acute AMR for few years. We reported a patient who received two courses of bortezomib for the treatment of an acute AMR associated with de novo HLA DSA that occurred 18 months after renal transplantation because of non-compliance. Graft biopsy revealed features of acute humoral rejection with plasmocyte infiltration and C4d staining. Bortezomib was associated with corticosteroid pulses, IVIgs, and PP. Despite this rapid management, the patient lost his graft and carried on dialysis. Bortezomib therapy in addition to current therapy of AMR is not always effective in the treatment for late acute AMR in renal transplantation. We discuss on the place of such a treatment and other therapeutic strategies in this indication. [ABSTRACT FROM AUTHOR]

Lymphocyte-activation gene-3 (LAG-3, CD223) is a marker for recently activated effector T cells. Activated T lymphocytes are of major importance in many autoimmune diseases and organ transplant rejection. Therefore, specifically depleting LAG-3 T cells might lead to targeted immunosuppression that would spare resting T cells while eliminating pathogenic activated T cells. We have shown previously that anti-LAG-3 antibodies sharing depleting as well as modulating activities inhibit heart allograft rejection in rats. Here, we have developed and characterized a cytotoxic LAG-3 chimeric antibody (chimeric A9H12), and evaluated its potential as a selective therapeutic depleting agent in a non-human primate model of delayed-type hypersensitivity (DTH). Chimeric A9H12 showed a high affinity to its antigen and depleted both cytomegalovirus (CMV)-activated CD4 and CD8 human T lymphocytes in vitro. In vivo, a single intravenous injection at either 1 or 0·1 mg/kg was sufficient to deplete LAG-3-activated T cells in lymph nodes and to prevent the T helper type 1 (Th1)-driven skin inflammation in a tuberculin-induced DTH model in baboons. T lymphocyte and macrophage infiltration into the skin was also reduced. The in vivo effect was long-lasting, as several weeks to months were required after injection to restore a positive reaction after antigen challenge. Our data confirm that LAG-3 is a promising therapeutic target for depleting antibodies that might lead to higher therapeutic indexes compared to traditional immunosuppressive agents in autoimmune diseases and transplantation. [ABSTRACT FROM AUTHOR]

In this review, we summarize the work published over the last 2 years using genetic modifications of animals in the field of xenotransplantation. Genetic engineering of the donor has become a powerful tool in xenotransplantation, both for the inactivation of one particular porcine gene and for the addition of human genes with the goal of overcoming xenogeneic barriers. We summarize the work relative to the knockout of the α1,3-galactosyltransferase gene, followed by genetic engineering aimed at reducing the humoral and cellular immune response, complement activation and coagulation. Finally, we report on the genetic modification of pigs to reduce porcine endogenous retrovirus infection risk in the xenogeneic context.Gene Therapy (2008) 15, 1247–1256; doi:10.1038/gt.2008.119 [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the potential usefulness of dynamic MR with echoplanar imaging (EPI) in assessing the renal function in patients with renal allografts.Material and Methods: Using a T1-weighted sequence, EPI was performed after injection of a Gd-chelate in 17 patients with normally functioning renal allografts. Time-intensity curves were plotted from the signal intensity (SI) measurements of the cortex and the medulla.Results: The pattern of corticomedullar differentiation (CMD) observed after contrast enhancement was divided into four phases using the T1-EPI. After a rapid decrease in the SI of cortical structures, and a subsequent return to precontrast levels, a gradual fall in the SI of the medulla was observed. The average time between the two periods of signal loss was 60 s.Conclusion: This study illustrated the potential use of dynamic T1-EPI to demonstrate contrast-induced CMD in renal allografts. [ABSTRACT FROM AUTHOR]