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Current opinion in organ transplantation [journal]
- The bile duct in donation after cardiac death donor liver transplant. [JOURNAL ARTICLE]
- Curr Opin Organ Transplant 2014 Aug; 19(4):447-452.
This review considers the biliary complications associated with liver transplantation using donation after cardiac death (DCD) donor grafts.The increasing use of DCD liver grafts with their increased incidence of biliary complications is discussed. The ethics of this greater use is briefly analysed. Recent animal and human study evidence to support the peribiliary vascular plexus' role in ischaemic cholangiopathy is reviewed. Recent advances in in-vivo and ex-vivo perfusion are explored. In particular, the latest theories regarding perfusion's peribiliary plexus preserving effects and the mechanism by which biliary regeneration may be promoted as a consequence are discussed.This article explores the need for DCD liver graft use and the associated biliary complications. The current theories regarding the cause of DCD biliary complications are reviewed, as are the current strategies to reduce them.
- Human leukocyte antigen epitope antigenicity and immunogenicity. [JOURNAL ARTICLE]
- Curr Opin Organ Transplant 2014 Aug; 19(4):428-435.
Human leukocyte antigen (HLA) antibodies are now recognized as being specific for epitopes which can be defined structurally with amino acid differences between HLA alleles. This article addresses two general perspectives of HLA epitopes namely antigenicity, that is their reactivity with antibody and immunogenicity, that is their ability of eliciting an antibody response.Single-antigen bead assays have shown that HLA antibodies recognize epitopes that are equivalent to eplets or corresponding to eplets paired with other residue configurations. There is now a website-based Registry of Antibody-Defined HLA Epitopes (http://www.epregistry.com.br). Residue differences within eplet-defined structural epitopes may also explain technique-dependent variations in antibody reactivity determined in Ig-binding, C1q-binding and lymphocytotoxicity assays.HLA antibody responses correlate with the numbers of eplets on mismatched HLA antigens, and the recently proposed nonself-self paradigm of epitope immunogenicity may explain the production of epitope-specific antibodies.These findings support the usefulness of HLA matching at the epitope level, including the identification of acceptable mismatches for sensitized patients and permissible mismatching for nonsensitized patients aimed to reduce HLA antibody responses.
- Epitope-based human leukocyte antigen matching for transplantation. [Journal Article]
- Curr Opin Organ Transplant 2014 Aug; 19(4):418-9.
- BK virus infection following kidney transplantation: an overview of risk factors, screening strategies, and therapeutic interventions. [JOURNAL ARTICLE]
- Curr Opin Organ Transplant 2014 Aug; 19(4):401-412.
In recipients of kidney transplants, the emergence of BK virus (BKV)-associated clinical syndromes, such as viruria, viremia, and BK nephropathy, coincided with the advent of potent immunosuppressive therapy. There is currently no standardized protocol for the management of BK viruria or viremia, or established BK nephropathy. Suggested risk factors for BKV replication and a literature overview on various treatment strategies for BKV-associated clinical syndromes are presented, followed by the authors' proposed approach for screening, monitoring, and treatment of post-transplant BKV infection.BKV infection can occur under all combinations of immunosuppressive therapy. Although both humoral and cellular immunity may be essential, BKV-specific T-cell immunity appears to play a pivotal role in controlling BKV replication. Monitoring BKV-specific immune response might prove useful in guiding therapeutic intervention. The beneficial effects of antiviral agents remain unclear. Development of T-cell or antibody-based vaccines against BKV is a subject of future research.In the absence of conclusive evidence that any particular immunosuppressive agent has a specific influence over another on BKV infection risk and the unclear benefit of antiviral agents, intensive monitoring of serum BKV using PCR and immunological containment of BKV replication should remain the mainstay of therapy. The routine recommendations of antiviral agents in the treatment of BKV-associated clinical syndromes await results of large prospective randomized trials.
- Editorial introductions. [JOURNAL ARTICLE]
- Curr Opin Organ Transplant 2014 Aug; 19(4):v.
- Chronic kidney disease and the aging population. [JOURNAL ARTICLE]
- Curr Opin Organ Transplant 2014 Jul 7.
- Drug minimization in transplantation: an opinion. [JOURNAL ARTICLE]
- Curr Opin Organ Transplant 2014 Jul 2.
- Insight into the role of mTOR and metabolism in T cells reveals new potential approaches to preventing graft rejection. [JOURNAL ARTICLE]
- Curr Opin Organ Transplant 2014 Jul 2.
In this review, we discuss the recent advances with regard to the mammalian target of rapamycin (mTOR) signaling pathway and focus on how this pathway modulates immune responses. Overall, these insights provide important clues in terms of strategically integrating mTOR and metabolic inhibitors into transplantation rejection protocols.mTOR is regulated by environmental cues and activates diverse downstream pathways to guide cell growth and fate. What has emerged from recent studies is that mechanistically mTOR directs T cell differentiation and function in part by regulating metabolic programs. Such findings not only inform us with regard to the metabolic demands of effector and memory T cells but also elucidate metabolic pathways that might be targeted to selectively regulate immune responses.Initial studies focused on the ability of the mTOR inhibitor rapamycin to suppress immune responses by inhibiting T cell proliferation. Since then, both pharmacologic and genetic studies have revealed a central role for mTOR in regulating T cell activation, differentiation, and function independent of proliferation. Specifically, it has become clear that mTOR plays an important role in regulating the metabolic machinery necessary for effector, regulatory, and memory T cell generation. As such, direct inhibition of metabolism may emerge as a potent and selective means of preventing graft rejection. This review will discuss new insights regarding the ability of downstream signaling pathways, including mTOR-dependent metabolic pathways in regulating T cell responses. Finally, we will discuss these new insights in the context of developing novel immunoregulatory regimens for transplantation.
- Recent developments in kidney transplantation in children. [JOURNAL ARTICLE]
- Curr Opin Organ Transplant 2014 Jul 2.
Renal transplantation in childhood is a well established procedure with excellent short-term outcomes. However, waiting times for transplantation are still relatively long if living donation cannot be performed, and long-term outcomes after transplantation have not significantly improved during the last decade.This review describes alternative modalities to improve donation rates such as en bloc kidney transplantation from young donors, ABO-incompatible transplantation and kidney paired donation. This review also deals with long-term post-transplant morbidities, such as follows: first, medication side-effects (metabolic syndrome, cardiovascular disease) and with the benefits of steroid and calcineurin inhibitor drug minimization; second, the deleterious impact of viral infections and their management and third, chronic antibody-mediated rejection, its therapeutic and prevention possibilities.Donor shortage and long-term morbidities, after transplantation, are still relevant issues in paediatric renal transplantation medicine. Significant research and efforts have been made to advance the field and create novel approaches for improvement of transplantation rates and post-transplant graft or patient survival. These modalities are to be established in the routine setting.
- Structural and electrostatic analysis of HLA B-cell epitopes: inference on immunogenicity and prediction of humoral alloresponses. [JOURNAL ARTICLE]
- Curr Opin Organ Transplant 2014 Jun 28.
The immunogenic capacity of donor human leukocyte antigen (HLA) to induce humoral immune responses is not an intrinsic property of the mismatched alloantigen but depends on the HLA phenotype of the recipient. In recent years, advances in molecular sequence technology and information from X-ray crystallography have enabled structural comparison of donor and recipient HLA type providing an opportunity for a more rational approach for determining HLA compatibility. In this article, we review studies investigating the molecular basis of antibody-antigen interactions and present computational approaches to determine the complex physiochemical and structural properties of B-cell epitopes.The relative immunogenicity of individual HLA mismatches may be predicted from analysis of polymorphic amino acids at continuous and discontinuous HLA sequence positions. The use of alloantigen sequence information alone, however, provides limited insight into key determinants of B-cell epitope immunogenicity, such as the orientation, accessibility and physiochemical properties of amino acid side chains. Advances in computational molecular modelling techniques now enable assessment of HLA-alloantibody interactions at the atomic level. Recent evidence supports a strong link between HLA B-cell epitope surface electrostatic potential and their immunogenicity.Assessment of the surface electrostatic properties of HLA alloantigens and computational analyses of HLA-alloantibody interactions represent a promising area for future research into the molecular basis of HLA immunogenicity and antigenicity.