Depletion of alloreactive B cells by drug- resistant chimeric alloantigen receptor T cells to prevent transplant rejection.

Antibody-mediated rejection (AMR) remains a major complication after solid organ transplantation (SOT). Current treatment options are inefficient and result in drastic impairment of the general immunity. To selectively eliminate responsible alloreactive B cells characterized by anti-donor-HLA B-cell receptors (BCRs), we generated T cells overcoming rejection by antibodies (CORA-Ts) engineered with a novel chimeric receptor comprising a truncated donor-HLA molecule as antigen recognition domain.

Prediction of Survival After Pediatric Cardiac Arrest Using Quantitative EEG and Machine Learning Techniques.

Background And Objectives: Early neuroprognostication in children with reduced consciousness after cardiac arrest (CA) is a major clinical challenge. EEG is frequently used for neuroprognostication in adults, but has not been sufficiently validated for this indication in children. Using machine learning techniques, we studied the predictive value of quantitative EEG (qEEG) features for survival 12 months after CA, based on EEG recordings obtained 24 hours after CA in children.

Risk Stratification Before Living Donor Kidney Transplantation in Patients With Preformed Donor-specific Antibodies by Different Crossmatch Methods.

Background: Preformed donor-specific HLA antibodies (DSA) are a well-known risk factor in kidney transplantation. There is still considerable debate, however, about the optimal risk stratification among patients with preformed DSA. Additionally, data on the prognostic value of different crossmatch assays in DSA-positive patients are scarce.

Human leukocyte antigen-DQA1*04:01 and rs2040406 variants are associated with elevated risk of childhood Burkitt lymphoma.

Burkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum. However, whether human leukocyte antigen (HLA) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi.

An Improved Protocol for Targeted Differentiation of Primed Human Induced Pluripotent Stem Cells into HLA-G-Expressing Trophoblasts to Enable the Modeling of Placenta-Related Disorders.

Abnormalities at any stage of trophoblast development may result in pregnancy-related complications. Many of these adverse outcomes are discovered later in pregnancy, but the underlying pathomechanisms are constituted during the first trimester. Acquiring developmentally relevant material to elucidate the disease mechanisms is difficult.

Lung transplantation despite preformed donor-specific antihuman leukocyte antigen antibodies: a 9-year single-center experience.

Pretransplant allosensitization to human leukocyte antigens (HLA) increases the recipient's waiting list time and mortality in lung transplantation. Rather than waiting for crossmatch-negative donors, since 2013, recipients with preformed donor-specific antiHLA antibodies (pfDSA) have been managed with repeated IgA- and IgM-enriched intravenous immunoglobulin (IgGAM) infusions, usually in combination with plasmapheresis before IgGAM and a single dose of antiCD20 antibody. This retrospective study presents our 9-year experience with patients transplanted with pfDSA.

A novel HLA-DPB1 allele, HLA-DPB1*1447:01, identified by next-generation sequencing.

HLA-DPB1*1447:01 differs from HLA-DPB1*04:01:01 by a single nucleotide in exon 2 from A to C at position 134.

Incidence of Air Leaks in Critically Ill Patients with Acute Hypoxemic Respiratory Failure Due to COVID-19.

Subcutaneous emphysema, pneumothorax and pneumomediastinum are well-known complications of invasive ventilation in patients with acute hypoxemic respiratory failure. We determined the incidences of air leaks that were visible on available chest images in a cohort of critically ill patients with acute hypoxemic respiratory failure due to coronavirus disease of 2019 (COVID-19) in a single-center cohort in the Netherlands. A total of 712 chest images from 154 patients were re-evaluated by a multidisciplinary team of independent assessors; there was a median of three (2-5) chest radiographs and a median of one (1-2) chest CT scans per patient.

Next-generation sequencing reveals a novel HLA-C allele, HLA-C*15:255.

HLA-C*15:255 differs from HLA-C*15:02:01 by five nucleotide substitutions located in exons 4 and 5.

Next generation sequencing reveals a novel HLA-C allele, HLA-C*16:201.

HLA-C*16:201 differs from HLA-HLA-C*16:01:01 by one nucleotide substitution in codon 73 (ACT ->GCT).

A novel null-allele, HLA-B*35:574N, containing a mutation in the start-codon.

HLA-B*35:574N contains a single nucleotide substitution at nucleotide position 2 (ATG to ACG).

HLA-C*07:1044N a novel allele, caused by a single nucleotide deletion in exon 3 of HLA-C*07:01:01:01.

HLA-C*07:1044N differs from HLA-C*07:01:01:01 by a single nucleotide deletion in exon 3, codon 124, nt. 442.

A novel HLA allele, HLA-A*03:420, identified by next-generation sequencing.

HLA-A*03:420 differs from HLA-A*03:01:01:01 by a single nucleotide in exon 1, codon -22.

Rapid Manufacturing of Highly Cytotoxic Clinical-Grade SARS-CoV-2-specific T Cell Products Covering SARS-CoV-2 and Its Variants for Adoptive T Cell Therapy.

Evaluation of the feasibility of SARS-CoV-2-specific T cell manufacturing for adoptive T cell transfer in COVID-19 patients at risk to develop severe disease. Antiviral SARS-CoV-2-specific T cells were detected in blood of convalescent COVID-19 patients following stimulation with PepTivator SARS-CoV-2 Select using Interferon-gamma Enzyme-Linked Immunospot (IFN-γ ELISpot), SARS-CoV-2 T Cell Analysis Kit (Whole Blood) and Cytokine Secretion Assay (CSA) and were characterized with respect to memory phenotype, activation state and cytotoxic potential by multicolor flow cytometry, quantitative real-time PCR and multiplex analyses. Clinical-grade SARS-CoV-2-specific T cell products were generated by stimulation with MACS GMP PepTivator SARS-CoV-2 Select using CliniMACS Prodigy and CliniMACS Cytokine Capture System (IFN-gamma) (CCS).

Heart transplantation across preformed donor-specific antibody barriers using a perioperative desensitization protocol.

Heart transplantation across preformed donor-specific HLA-antibody barriers is associated with impaired short- and long-term survival. Therefore, in recipients with preformed anti-HLA antibodies, waiting for crossmatch-negative donors is standard practice. As an alternative strategy, recipients with preformed anti-HLA donor specific antibodies have been managed at our institutions with a perioperative desensitization regimen.

Defining integrity: An approach and military application.

Personnel selection research has seen an increasing interest in integrity tests. Although these tests have been found to predict a variety of workplace criteria, a long-standing criticism of integrity tests is their criterion-focussed nature. A construct-oriented approach to integrity test development involves identifying important elements of integrity and developing content to reflect those elements.

Reimagining Postdiagnostic Care and Support in Young-Onset Dementia.

Although dementia has a profound impact in general, young-onset dementia causes additional problems and challenges as people are affected in their prime years. Awareness has increased that people with young-onset dementia and their families have specific care needs and dedicated services are necessary to accommodate those needs. However, in many countries, age-appropriate care and support for people with young-onset dementia is still largely unavailable.

B cell depletion impairs vaccination-induced CD8 T cell responses in a type I interferon-dependent manner.

Objectives: The monoclonal anti-CD20 antibody rituximab is frequently applied in the treatment of lymphoma as well as autoimmune diseases and confers efficient depletion of recirculating B cells. Correspondingly, B cell-depleted patients barely mount de novo antibody responses during infections or vaccinations. Therefore, efficient immune responses of B cell-depleted patients largely depend on protective T cell responses.

Steering Transplant Immunosuppression by Measuring Virus-Specific T Cell Levels: The Randomized, Controlled IVIST Trial.

Background: Pharmacokinetic monitoring is insufficient to estimate the intensity of immunosuppression after transplantation. Virus-specific T cells correlate with both virus-specific and general cellular immune defense. Additional steering of immunosuppressive therapy by virus-specific T cell levels might optimize dosing of immunosuppressants.

Two novel antithetical KN blood group antigens may contribute to more than a quarter of all KN antisera in Europe.

Background: All antigens described in the KN blood group system are located in the long homologous repeat D (LHR-D) of complement receptor 1 (CR1). While there have been reports that some sera react only with the long homologous repeat C (LHR-C), the antigens in LHR-C are unknown.

Study Design And Methods: Recombinant LHR-C and LHR-D were used to identify antibodies directed against LHR-C of CR1, into which a point mutation was introduced to characterize the underlying blood group antigens.

Non-invasive screening for subclinical liver graft injury in adults via donor-specific anti-HLA antibodies.

The majority of liver grafts exhibit abnormal histological findings late after transplantation, even when liver enzymes are normal. Such subclinical graft injuries were associated with rejection and fibrosis progression in recent studies. The identification of non-invasive biomarkers for subclinical graft injury might help to individualize immunosuppression.

Generating low immunogenic pig pancreatic islet cell clusters for xenotransplantation.

Xenotransplantation of pancreatic islets offers a promising alternative to overcome the shortage of allogeneic donors. Despite significant advances, either immune rejection or oxygen supply in immune protected encapsulated islets remains major bottlenecks for clinical application. To decrease xenogeneic immune responses, we generated tissue engineered swine leucocyte antigen (SLA)-silenced islet cell clusters (ICC).

Variation in the Human Leukocyte Antigen system and risk for endemic Burkitt lymphoma in northern Uganda.

Endemic Burkitt lymphoma (eBL) is an aggressive childhood B-cell lymphoma associated with Plasmodium falciparum (Pf) malaria and Epstein-Barr virus (EBV) infections. Variation in the Human Leukocyte Antigen (HLA) system is suspected to play a role, but assessments using less accurate serology-based HLA typing techniques in small studies yielded conflicting results. We studied 200 eBL cases and 400 controls aged 0-15 years enrolled in northern Uganda and typed by accurate high-resolution HLA sequencing methods.

Six-year experience with treatment of early donor-specific anti-HLA antibodies in pediatric lung transplantation using a human immunoglobulin-based protocol.

Objectives: Experience with the treatment of early donor-specific anti-HLA antibodies (eDSA) after lung transplantation in children is very limited. At our institution, we have treated patients with eDSA since 2013 with successive infusions of intravenous human immunoglobulins (IVIG), combined in some cases with a single dose of Rituximab and plasmapheresis (therapeutic plasma exchange [tPE]) or immunoabsorption. The aim of this study was to present the 6-year results of IVIG-based therapy in pediatric lung recipients.

Increased frequency of CD4 CD25 CD127 T cells early after lung transplant is associated with improved graft survival - a retrospective study.

In this retrospective study, we analyzed the presence of any association of three CD4 CD25 regulatory T-cell subpopulations at 3 weeks after lung transplantation with the later incidence of chronic lung allograft dysfunction and graft survival. Among lung-transplanted patients between January 2009 and April 2018, only patients with sufficient T-cell measurements at 3 weeks after transplantation were included into the study. Putative regulatory T cells were defined as CD4 CD25 T cells, detected in peripheral blood and further analyzed for CD127 , FoxP3 , and CD152 using fluorescence-activated cell sorting (FACS) analysis.