The first modified Delphi consensus statement on sleeve gastrectomy.

Introduction: Sleeve gastrectomy (SG) is the commonest bariatric procedure worldwide. Yet there is significant variation in practice concerning its various aspects. This paper report results from the first modified Delphi consensus-building exercise on SG.

Predicting Humoral Alloimmunity from Differences in Donor and Recipient HLA Surface Electrostatic Potential.

In transplantation, development of humoral alloimmunity against donor HLA is a major cause of organ transplant failure, but our ability to assess the immunological risk associated with a potential donor-recipient HLA combination is limited. We hypothesized that the capacity of donor HLA to induce a specific alloantibody response depends on their structural and physicochemical dissimilarity compared with recipient HLA. To test this hypothesis, we first developed a novel computational scoring system that enables quantitative assessment of surface electrostatic potential differences between donor and recipient HLA molecules at the tertiary structure level [three-dimensional electrostatic mismatch score (EMS-3D)].

Sensitization in Transplantation: Assessment of Risk (STAR) 2017 Working Group Meeting Report.

The presence of preexisting (memory) or de novo donor-specific HLA antibodies (DSAs) is a known barrier to successful long-term organ transplantation. Yet, despite the fact that laboratory tools and our understanding of histocompatibility have advanced significantly in recent years, the criteria to define presence of a DSA and assign a level of risk for a given DSA vary markedly between centers. A collaborative effort between the American Society for Histocompatibility and Immunogenetics and the American Society of Transplantation provided the logistical support for generating a dedicated multidisciplinary working group, which included experts in histocompatibility as well as kidney, liver, heart, and lung transplantation.

A Comparison of HLA Molecular Mismatch Methods to Determine HLA Immunogenicity.

Background: Antibody-mediated rejection is a major cause of premature graft loss in kidney transplantation. Multiple scoring systems are available to assess the HLA mismatch between donors and recipients at the molecular level; however, their correlation with the development of de novo donor-specific antibody (dnDSA) has not been compared in recipients on active immunosuppression.

Methods: HLA-DRβ1/3/4/5/DQα1β1 molecular mismatch was determined using eplet analysis, amino acid mismatch, and electrostatic mismatch for 596 renal transplant recipients and correlated with HLA-DR/DQ dnDSA development.

Technical Limitations of the C1q Single-Antigen Bead Assay to Detect Complement Binding HLA-Specific Antibodies.

Background: Solid-phase assays to distinguish complement binding from noncomplement binding HLA-specific antibodies have been introduced, but technical limitations may compromise their interpretation. We have examined the extent to which C1q-binding to HLA-class I single-antigen beads (SAB) is influenced by denatured HLA on SAB, antibody titre, and complement interference that causes a misleading low assessment of HLA-specific antibody levels.

Methods: Sera from 25 highly sensitized patients were tested using Luminex IgG-SAB and C1q-SAB assays.

Logistical Factors Influencing Cold Ischemia Times in Deceased Donor Kidney Transplants.

Background: Prolonged cold ischemia time (CIT) is associated with a significant risk of short- and long-term graft failure in deceased donor kidney transplants across the world. The aim of this prospective longitudinal study was to determine the importance of logistical factors on CIT.

Method: Data on 1763 transplants were collected prospectively over 14 months from personnel in 16 transplant centers, 19 histocompatibility and immunogenetics laboratories, transport providers, and National Health Service Blood and Transplant.

Setting Up a Haplobank: Issues and Solutions.

The development of induced pluripotent stem cells offers the possibility of the scalable manufacture of cellular therapies for regenerative medicine. Moreover, donors can be selected on the basis of major transplant antigen systems to match the widest possible number of recipients worldwide, reducing the likely risk of immunological rejection and the degree of immune suppression or tolerance required. If such cell lines are to be broadly available, there will need to be mutual recognition of common standards across different jurisdictions.

The efficacy of bariatric surgery performed in the public sector for obese patients with comorbid conditions.

Objective: To determine the efficacy of bariatric surgery in the public sector for the treatment of complicated obesity.

Design, Setting And Participants: A longitudinal observational study of obese participants with comorbid conditions, aged 21-73 years, who underwent publicly funded bariatric surgery. Data were extracted from clinical databases (1 October 2009 to 1 September 2013) and recorded at seven time points.

Transplantation between monozygotic twins: how identical are they?

Advances in developmental biology have shown that monozygous twins may not be as phenotypically identical as once believed, and the mechanisms responsible for such differences are now becoming clearer. Whether such phenotypic differences are capable of triggering graft rejection of an organ transplanted between identical twins remains unknown but the risks seem low, and long-term transplant outcome is excellent. Available evidence to guide immunosuppressive therapy in this setting is limited but a prudent approach would include the use of steroids together with a calcineurin inhibitor after transplantation.

Structural and electrostatic analysis of HLA B-cell epitopes: inference on immunogenicity and prediction of humoral alloresponses.

Purpose Of Review: 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.

Impact of donor mismatches at individual HLA-A, -B, -C, -DR, and -DQ loci on the development of HLA-specific antibodies in patients listed for repeat renal transplantation.

We have analyzed the relationship between donor mismatches at each HLA locus and development of HLA locus-specific antibodies in patients listed for repeat transplantation. HLA antibody screening was undertaken using single-antigen beads in 131 kidney transplant recipients returning to the transplant waiting list following first graft failure. The number of HLA mismatches and the calculated reaction frequency of antibody reactivity against 10,000 consecutive deceased organ donors were determined for each HLA locus.

LILRB2 interaction with HLA class I correlates with control of HIV-1 infection.

Natural progression of HIV-1 infection depends on genetic variation in the human major histocompatibility complex (MHC) class I locus, and the CD8+ T cell response is thought to be a primary mechanism of this effect. However, polymorphism within the MHC may also alter innate immune activity against human immunodeficiency virus type 1 (HIV-1) by changing interactions of human leukocyte antigen (HLA) class I molecules with leukocyte immunoglobulin-like receptors (LILR), a group of immunoregulatory receptors mainly expressed on myelomonocytic cells including dendritic cells (DCs). We used previously characterized HLA allotype-specific binding capacities of LILRB1 and LILRB2 as well as data from a large cohort of HIV-1-infected individuals (N = 5126) to test whether LILR-HLA class I interactions influence viral load in HIV-1 infection.

Laparoscopic sleeve gastrectomy: review of 500 cases in single surgeon Australian practice.

Introduction: Reported results and techniques of laparoscopic sleeve gastrectomy (LSG) are variable. Our objective was to assess results of weight loss, complications and reflux in a large consecutive series of LSG, describing technical detail which contributed to outcomes.

Methods: Retrospective review of prospectively collected data of 500 consecutive patients undergoing LSG.

Toward the development of a global induced pluripotent stem cell library.

The ability to preselect the donor genotype of iPSC lines provides important opportunities for immune matching in cell therapy. Here we propose that an international assessment should be made of how immune incompatibility can best be managed and how a network of GMP HLA homozygous haplobanks could be operated.

Elevated pretransplantation soluble BAFF is associated with an increased risk of acute antibody-mediated rejection.

Background: B cells play an important role in renal allograft pathology, particularly in acute and chronic antibody-mediated rejection (AMR). B-cell activating factor belonging to the tumor necrosis factor family (BAFF; also known as BLyS) is a cytokine that enhances B-cell survival and proliferation.

Methods: We analyzed serum BAFF levels in 32 patients undergoing antibody-incompatible (Ai) renal transplantation and 319 antibody-compatible transplant recipients and sought to determine whether there was a correlation with acute rejection and with transplant function and survival.

Consensus guidelines on the testing and clinical management issues associated with HLA and non-HLA antibodies in transplantation.

Background: The introduction of solid-phase immunoassay (SPI) technology for the detection and characterization of human leukocyte antigen (HLA) antibodies in transplantation while providing greater sensitivity than was obtainable by complement-dependent lymphocytotoxicity (CDC) assays has resulted in a new paradigm with respect to the interpretation of donor-specific antibodies (DSA). Although the SPI assay performed on the Luminex instrument (hereafter referred to as the Luminex assay), in particular, has permitted the detection of antibodies not detectable by CDC, the clinical significance of these antibodies is incompletely understood. Nevertheless, the detection of these antibodies has led to changes in the clinical management of sensitized patients.

Generating an iPSC bank for HLA-matched tissue transplantation based on known donor and recipient HLA types.

The likelihood for immunological rejection of Human Leukocyte Antigens (HLA)-mismatched induced pluripotent stem cells (iPSCs) limits their therapeutic potential. Here we show how a tissue bank from 150 selected homozygous HLA-typed volunteers could match 93% of the UK population with a minimal requirement for immunosuppression. Our model provides a practical approach for using existing HLA-typed samples to generate an iPSC stem cell bank that circumvents prospective typing of a large number of individuals.

High-resolution, three-dimensional modeling of human leukocyte antigen class I structure and surface electrostatic potential reveals the molecular basis for alloantibody binding epitopes.

The potential of human leukocyte antigens (HLA) to stimulate humoral alloimmunity depends on the orientation, accessibility and physiochemical properties of polymorphic amino acids. We have generated high-resolution structural and physiochemical models of all common HLA class I alleles and analyzed the impact of amino acid polymorphisms on surface electrostatic potential. Atomic resolution three-dimensional structural models of HLA class I molecules were generated using the MODELLER computer algorithm.