Peptide Sharing Between CMV and Mismatched HLA Class I Peptides Promotes Early T-Cell-Mediated Rejection After Kidney Transplantation.

Cytomegalovirus (CMV) infection is related to acute rejection and graft loss after kidney transplantation, though the underlying mechanism remains largely unknown. Some CMV strains produce a peptide that is identical to a peptide sequence found in the leader peptide of specific HLA-A and -C alleles. In this retrospective study of 351 kidney transplantations, we explored whether CMV-seropositive recipients without the VMAPRTLIL, VMAPRTLLL or VMAPRTLVL HLA class I leader peptide receiving a transplant from a donor with this peptide, faced an increased risk of T-cell-mediated rejection (TCMR) in the first 90 days after transplantation.

Paternal HLA-Derived Epitopes and Live Birth in Secondary Recurrent Pregnancy Loss: New Insights From a Clinical Trial.

Recurrent pregnancy loss (RPL), defined as two or more pregnancy losses before the 24th week of gestation, affects 1%-3% of women worldwide. Approximately, 40% of RPL cases are secondary RPL (sRPL), where women have given birth before facing pregnancy losses. The underlying causes of RPL remain unclear, but immune-related factors may play a role.

Experimental Data on PIRCHE and T-Cell Reactivity: HLA-DPB1-Derived Peptides Identified by PIRCHE-I Show Binding to HLA-A*02:01 in vitro and T-Cell Activation in vivo.

Introduction: Human leukocyte antigen (HLA)-DPB1 mismatches during hematopoietic stem cell transplantation (HSCT) with an unrelated donor result in an increased risk for the development of graft-versus-host disease (GvHD). The number of CD8 T-cell epitopes available for indirect allorecognition as predicted by the PIRCHE algorithm has been shown to be associated with GvHD development. As a proof of principle, PIRCHE-I predictions for HLA-DPB1 mismatches were validated in vitro and in vivo.

The Value of Single-cell Technologies in Solid Organ Transplantation Studies.

Single-cell technologies open up new opportunities to explore the behavior of cells at the individual level. For solid organ transplantation, single-cell technologies can provide in-depth insights into the underlying mechanisms of the immunological processes involved in alloimmune responses after transplantation by investigating the role of individual cells in tolerance and rejection. Here, we review the value of single-cell technologies, including cytometry by time-of-flight and single-cell RNA sequencing, in the context of solid organ transplantation research.

T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation.

CD4 T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4 memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4 memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome.

Computational Eurotransplant kidney allocation simulations demonstrate the feasibility and benefit of T-cell epitope matching.

The EuroTransplant Kidney Allocation System (ETKAS) aims at allocating organs to patients on the waiting list fairly whilst optimizing HLA match grades. ETKAS currently considers the number of HLA-A, -B, -DR mismatches. Evidently, epitope matching is biologically and clinically more relevant.

PIRCHE-II: an algorithm to predict indirectly recognizable HLA epitopes in solid organ transplantation.

Human leukocyte antigen (HLA) mismatches between donors and recipients may lead to alloreactivity after solid organ transplantation. Over the last few decades, our knowledge of the complexity of the HLA system has dramatically increased, as numerous new HLA alleles have been identified. As a result, the likelihood of alloreactive responses towards HLA mismatches after solid organ transplantation cannot easily be assessed.

Exploratory Study of Predicted Indirectly ReCognizable HLA Epitopes in Mismatched Hematopoietic Cell Transplantations.

HLA-mismatches in hematopoietic stem-cell transplantation are associated with an impaired overall survival (OS). The aim of this study is to explore whether the Predicted Indirectly ReCognizable HLA-Epitopes (PIRCHE) algorithm can be used to identify HLA-mismatches that are related to an impaired transplant outcome. PIRCHE are computationally predicted peptides derived from the patient's mismatched-HLA molecules that can be presented by donor-patient shared HLA.

PIRCHE-II Is Related to Graft Failure after Kidney Transplantation.

Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in donor-specific HLA antibodies formation after kidney transplantation.

Computational Approaches to Facilitate Epitope-Based HLA Matching in Solid Organ Transplantation.

Epitope-based HLA matching has been emerged over the last few years as an improved method for HLA matching in solid organ transplantation. The epitope-based matching concept has been incorporated in both the PIRCHE-II and the HLAMatchmaker algorithm to find the most suitable donor for a recipient. For these algorithms, high-resolution HLA genotype data of both donor and recipient is required.

A Previous Miscarriage and a Previous Successful Pregnancy Have a Different Impact on HLA Antibody Formation during a Subsequent Successful Pregnancy.

Inherited paternal HLA antigens from the semi-allogeneic fetus may trigger maternal immune responses during pregnancy, leading to the production of child-specific HLA antibodies. The prevalence of these HLA antibodies increases with the number of successful pregnancies. In the present study, we investigated the effect of a single prior miscarriage on HLA antibody formation during a subsequent successful pregnancy.

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.

Completion of HLA protein sequences by automated homology-based nearest-neighbor extrapolation of HLA database sequences.

The IMGT/HLA database contains every publicly available HLA sequence. However, most of these HLA protein sequences are restricted to the alpha-1/alpha-2 domain for HLA class-I and alpha-1/beta-1 domain for HLA class-II. Nevertheless, also polymorphism outside these domains may play a role in alloreactivity after transplantation.

Immunogenetic factors in the selection of cord blood units for transplantation: current search strategies and future perspectives.

Hematopoietic stem cell transplantation is currently used as a curative treatment for patients with malignant and non-malignant hematologic diseases. Human leukocyte antigen (HLA) matching is a major determinant for hematopoietic stem cell transplantation outcome. For patients lacking a fully HLA-matched donor, umbilical cord blood (UCB) units are alternative sources of hematopoietic stem cells because UCB transplantation allows a less stringent HLA matching.

Predicting alloreactivity in transplantation.

Human leukocyte Antigen (HLA) mismatching leads to severe complications after solid-organ transplantation and hematopoietic stem-cell transplantation. The alloreactive responses underlying the posttransplantation complications include both direct recognition of allogeneic HLA by HLA-specific alloantibodies and T cells and indirect T-cell recognition. However, the immunogenicity of HLA mismatches is highly variable; some HLA mismatches lead to severe clinical B-cell- and T-cell-mediated alloreactivity, whereas others are well tolerated.

Active matrix metalloprotease-9 is associated with the collagen capsule surrounding the Madurella mycetomatis grain in mycetoma.

Madurella mycetomatis is the main causative organism of eumycetoma, a persistent, progressive granulomatous infection. After subcutaneous inoculation M. mycetomatis organizes itself in grains inside a granuloma with excessive collagen accumulation surrounding it.