High resolution HLA genotyping with third generation sequencing technology-A multicentre study.

Molecular HLA typing techniques are currently undergoing a rapid evolution. While real-time PCR is established as the standard method in tissue typing laboratories regarding allocation of solid organs, next generation sequencing (NGS) for high-resolution HLA typing is becoming indispensable but is not yet suitable for deceased donors. By contrast, high-resolution typing is essential for stem cell transplantation and is increasingly required for questions relating to various disease associations.

Pre-transplant donor specific antibodies in ABO incompatible kidney transplantation - data from the Swiss transplant cohort study.

Background: Living donor (LD) kidney transplantation in the setting of ABO blood group incompatibility (ABOi) has been previously reported to be associated with increased risk for antibody-mediated rejection (ABMR). It is however unclear if the presence of pre-transplant donor specific antibodies (DSA) works as an additive risk factor in the setting of ABOi and if DSA positive ABOi transplants have a significantly worse long-term outcome as compared with ABO compatible (ABOc) DSA positive transplants.

Methods: We investigated the effect of pre-transplant DSA in the ABOi and ABOc setting on the risk of antibody-mediated rejection (ABMR) and graft loss in a cohort of 952 LD kidney transplants.

Donation type and the effect of pre-transplant donor specific antibodies - Data from the Swiss Transplant Cohort Study.

Introduction: The type of donation may affect how susceptible a donor kidney is to injury from pre-existing alloimmunity. Many centers are, therefore, reluctant to perform donor specific antibody (DSA) positive transplantations in the setting of donation after circulatory death (DCD). There are, however, no large studies comparing the impact of pre-transplant DSA stratified on donation type in a cohort with a complete virtual cross-match and long-term follow-up of transplant outcome.

The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation - Data from the Swiss transplant cohort study.

Background: Pre-transplant donor specific antibodies (DSA), directed at non-self human leukocyte antigen (HLA) protein variants present in the donor organ, have been associated with worse outcomes in kidney transplantation. The impact of the mean fluorescence intensity (MFI) and the target HLA antigen of the detected DSA has, however, not been conclusively studied in a large cohort with a complete virtual cross-match (vXM).

Methods: We investigated the effect of pre-transplant DSA on the risk of antibody-mediated rejection (ABMR), graft loss, and the rate of eGFR decline in 411 DSA positive transplants and 1804 DSA negative controls.

Pre-transplant donor-specific HLA antibodies and risk for poor first-year renal transplant outcomes: results from the Swiss Transplant Cohort Study.

The aim of this study was to analyze first year renal outcomes in a nationwide prospective multicenter cohort comprising 2215 renal transplants, with a special emphasis on the presence of pre-transplant donor-specific HLA antibodies (DSA). All transplants had a complete virtual crossmatch and DSA were detected in 19% (411/2215). The investigated composite endpoint was a poor first-year outcome defined as (i) allograft failure or (ii) death or (iii) poor allograft function (eGFR ≤25 ml/min/1.

Analysis of biological models to predict clinical outcomes based on HLA-DPB1 disparities in unrelated transplantation.

HLA compatibility is a key factor for survival after unrelated hematopoietic stem cell transplantation (HSCT). HLA-A, -B, -C, -DRB1, and -DQB1 are usually matched between donor and recipient. By contrast, HLA-DPB1 mismatches are frequent, although it is feasible to optimize donor selection and DPB1 matching with prospective typing.

Peripheral Donor-specific Antibodies Are Associated With Histology and Cellular Subtypes in Protocol Liver Biopsies of Pediatric Recipients.

Background: The cellular infiltrate in protocol liver biopsies (PB) following pediatric liver transplantation remains mostly uncharacterized, yet there is increasing concern about the role of inflammation and fibrosis in long-term liver allografts. We aimed to define cell types in PB and to analyze their relationship with donor-specific antibodies (DSA) and histological phenotype.

Methods: PB were performed at least 1 year after transplantation.

Correction: High-resolution HLA phased haplotype frequencies to predict the success of unrelated donor searches and clinical outcome following hematopoietic stem cell transplantation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Preformed and de novo DSA are associated with T-cell-mediated rejection in pediatric liver transplant recipients requiring clinically indicated liver biopsy.

Despite growing interest about the impact of donor-specific HLA antibodies (DSA) in LT limited data are available for pediatric recipients. Our aim was to perform a retrospective single-center chart review of children (0-16 years) having undergone LT between January 1, 2005 and December 31, 2017, to characterize DSA, to identify factors associated with the development of de novo DSA, and to analyze potential associations with the diagnosis of TCMR. Information on patient- and donor-characteristics and LB reports were analyzed retrospectively.

High-resolution HLA phased haplotype frequencies to predict the success of unrelated donor searches and clinical outcome following hematopoietic stem cell transplantation.

HLA matching is a critical factor for successful allogeneic hematopoietic stem cell transplantation. For unrelated donor searches, matching is usually based on high-resolution typing at five HLA loci, looking for a 10/10 match. Some studies have proposed that further matching at the haplotype level could be beneficial for clinical outcome.

Identification of seven novel HLA class I and II alleles.

Seven novel alleles were identified using two next generation sequencing technologies. Three alleles were confirmed.

Factors associated with immune hemolytic anemia after pediatric liver transplantation.

Immune-mediated hemolytic anemia following SOT is a rare disorder, the risk factors for which are unknown. Our purpose was to analyze a seemingly increased incidence in our center with the aim to identify predisposing factors. This recipients single-center retrospective study reviewed the medical records of 96 pediatric LT between 2000 and 2013.

Clinical and histological evolution after de novo donor-specific anti-human leukocyte antigen antibodies: a single centre retrospective study.

Background: Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) can be preformed or de novo (dn). Strategies to manage preformed DSA are well described, but data on the management and outcomes of dnDSA are lacking.

Methods: We performed a retrospective analysis of data from a single centre of the management and outcomes of 22 patients in whom a dnDSA was identified with contemporary and follow up biopsies.

Identification of 3 novel HLA-B alleles: B*08:173, B*18:72:03 and B*53:05:02.

A total of 3 novel human leukocyte antigen-B (HLA-B) alleles were detected by next generation sequencing and confirmed by monoallelic sequencing.

Immunogenicity of Anti-HLA Antibodies in Pancreas and Islet Transplantation.

The aim of the current study was to characterize the anti-HLA antibodies before and after pancreatic islet or pancreas transplantation. We assessed the risk of anti-donor-specific antibody (DSA) sensitization in a single-center, retrospective clinical study at Geneva University Hospital. Data regarding clinical characteristics, graft outcome, HLA mismatch, donor HLA immunogenicity, and anti-HLA antibody characteristics were collected.

Kidney paired donation: a plea for a Swiss National Programme.

Growing incidence of end-stage renal disease, shortage of kidneys from deceased donors and a better outcome for recipients of kidneys from living donor have led many centres worldwide to favour living donor kidney transplantation programmes. Although criteria for living donation have greatly evolved in recent years with acceptance of related and unrelated donors, an immunological incompatibility, either due to ABO incompatibility and/or to positive cross-match, between a living donor and the intended recipient, could impede up to 40% of such procedures. To avoid refusal of willing and healthy living donors, a number of strategies have emerged to overcome immunological incompatibilities.

Expression of killer cell immunoglobulin-like receptors (KIRs) by natural killer cells during acute CMV infection after kidney transplantation.

Human cytomegalovirus (CMV) infection may be a serious complication related to immunosuppression after solid organ transplantation. Due to their cytotoxicity, T-cells and natural killer (NK) cells target and clear the virus from CMV-infected cells. Although immunosuppressive drugs suppress T-cell proliferation and activation, they do not affect NK cells that are crucial for controlling the infection.

Late antibody-mediated rejection by de novo donor HLA-DP-specific antibody after renal transplantation: a case report.

The role of donor HLA-DP-specific antibodies after renal transplantation is controversial, and only preformed HLA-DP-specific antibodies have been shown to mediate rejection. Here we present a case of late humoral rejection mediated by de novo donor HLA-DP-specific antibodies in a non-sensitized recipient. This unique case demonstrates the pathogenic role of de novo anti-DP antibodies and suggests that HLA-DP matching might be relevant for renal transplantation.