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.

Correction: Broadly directed SARS-CoV-2-specific CD4+ T cell response includes frequently detected peptide specificities within the membrane and nucleoprotein in patients with acute and resolved COVID-19.

[This corrects the article DOI: 10.1371/journal.ppat.

Concordance with established tests and reproducibility of results obtained with a new single antigen chip array for HLA antibody detection (HISTO SPOT® HLA AB).

The purpose of this study was to analyze performance of a new single antigen chip array system (HISTO SPOT® HLA AB) developed for HLA antibody detection and compare with results obtained using single antigen Luminex-based systems and serum samples from the Eurotransplant external proficiency testing scheme. Results were analysed from 11 independent Eurotransplant laboratories using HISTO SPOT® HLA AB utilising the Eurotransplant external proficiency testing (EPT) sera and these were compared to published results from 67 labs using the Luminex-based technologies. In addition, QC results from different batches of the test were analysed.

Detection of EXP1-Specific CD4+ T Cell Responses Directed Against a Broad Range of Epitopes Including Two Promiscuous MHC Class II Binders During Acute Malaria.

T cells are thought to play a major role in conferring immunity against malaria. This study aimed to comprehensively define the breadth and specificity of the -specific CD4+ T cell response directed against the exported protein 1 (EXP1) in a cohort of patients diagnosed with acute malaria. Peripheral blood mononuclear cells of 44 patients acutely infected with , and of one patient infected with , were stimulated and cultured with an overlapping set of 31 -specific 13-17-mer peptides covering the entire EXP1 sequence.

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene polymorphisms in liver transplant donors and impact on acute cellular liver transplant rejection.

The PTPN22 gene encodes the lymphoid protein tyrosine phosphatase involved in regulation the immune response. The single nucleotide polymorphisms (SNPs) rs1217388, rs1310182, rs2476601, and rs2488457 are located within the PTPN22 gene. We investigated whether these SNPs in liver transplant donors are associated with acute cellular rejection in the recipients.

HCV-specific CD4+ T cells of patients with acute and chronic HCV infection display high expression of TIGIT and other co-inhibitory molecules.

The combined regulation of a network of inhibitory and activating T cell receptors may be a critical step in the development of chronic HCV infection. Ex vivo HCV MHC class I + II tetramer staining and bead-enrichment was performed with baseline and longitudinal PBMC samples of a cohort of patients with acute, chronic and spontaneously resolved HCV infection to assess the expression pattern of the co-inhibitory molecule TIGIT together with PD-1, BTLA, Tim-3, as well as OX40 and CD226 (DNAM-1) of HCV-specific CD4+ T cells, and in a subset of patients of HCV-specific CD8+ T cells. As the main result, we found a higher expression level of TIGIT+ PD-1+ on HCV-specific CD4+ T cells during acute and chronic HCV infection compared to patients with spontaneously resolved HCV infection (p < 0,0001).

Preformed Donor-Specific HLA Antibodies in Living and Deceased Donor Transplantation: A Multicenter Study.

Background And Objectives: The prognostic value of preformed donor-specific HLA antibodies (DSA), which are only detectable by sensitive methods, remains controversial for kidney transplantation.

Design, Setting, Participants, & Measurements: The outcome of 4233 consecutive kidney transplants performed between 2012 and 2015 in 18 German transplant centers was evaluated. Most centers used a stepwise pretransplant antibody screening with bead array tests and differentiation of positive samples by single antigen assays.

Limited impact of pre-existing donor specific HLA-antibodies (DSA) on long term allograft survival after first adult liver transplantation.

The relevance of pre-existing HLA-antibodies (HLA-Ab) in liver transplantation (LTx) is controversial. While livers are allocated without HLA match or preoperative crossmatch testing, several studies point to an impact of donor specific antibodies (DSA) for acute rejection, bile duct complications or even graft loss. To investigate the role of DSA in long term liver allograft survival we analysed 177 pre transplant sera of first LTx patients with Luminex single antigen technology defining a MFI of >1500 as positive.

Differential virus-specific CD8 T-cell epitope repertoire in hepatitis C virus genotype 1 versus 4.

Virus-specific CD8 T-cell responses play an important role in the outcome of hepatitis C virus (HCV) infection. To date, most HCV-specific CD8 T-cell epitopes have been defined in HCV genotype 1 infection. In contrast, the HCV genotype 4-specific CD8 T-cell response is poorly defined.

Polymorphisms of the human platelet antigen-1, -2, -3, -5, and -15 systems and acute cellular liver transplant rejection.

The human platelet antigen (HPA)-1, -2, -3, -5, and -15 systems are characterized as polymorphic alloantigens expressed on platelets and endothelial cells. In this retrospective study, we investigated, whether HPA-1, -2, -3, -5, and -15 incompatibilities are associated with acute cellular liver transplant rejection. A total of 96 Caucasian liver transplant recipients and corresponding donors were analyzed, 43 with biopsy proven acute cellular rejection (BPAR) and 53 without acute cellular rejection (No-BPAR).

Assignment of C1q-binding HLA antibodies as unacceptable HLA antigens avoids positive CDC-crossmatches prior to transplantation of deceased donor organs.

Soon, a virtual crossmatch shall replace the complement-dependent cytotoxicity (CDC) allocation crossmatch in the Eurotransplant region. To prevent positive CDC-crossmatches in the recipient centre, careful definition of unacceptable antigens is necessary. For highly sensitized patients, this is difficult by CDC alone.

De novo mTOR inhibitor-based immunosuppression in ABO-incompatible kidney transplantation.

ABO-incompatible (ABOi) kidney transplantation (KTx) has become an accepted therapeutic option in renal replacement therapy for patients without a blood group-compatible living donor. Using different desensitization strategies, most centers apply B-cell depletion with rituximab and maintenance immunosuppression (IS) with tacrolimus and mycophenolic acid. This high load of total IS leads to an increased rate of surgical complications and virus infections in ABOi patients.

High B-cell activating factor is not associated with worse 3-year graft outcome in blood group-incompatible kidney transplantation with rituximab induction.

B cells and their regulation by B-cell activating factor BAFF are of growing interest in kidney transplantation (KTx). There is evidence that high serum (s) BAFF leads to increased allosensitization and impaired long-term graft function. We prospectively investigated sBAFF, peripheral blood lymphocytes (PBL), and donor-specific HLA antibodies (DSA) in patients after ABOi with B-cell depleting rituximab induction treatment and compared them to a group of blood group-compatible (ABOc) living donor kidney recipients.

Tetramer enrichment reveals the presence of phenotypically diverse hepatitis C virus-specific CD8+ T cells in chronic infection.

Unlabelled: Virus-specific CD8(+) T cells are rarely detectable ex vivo by conventional methods during chronic hepatitis C virus (HCV) infection. In this study, however, we were able to detect and characterize HCV-specific CD8(+) T cells in all chronically HCV genotype 1a-infected, HLA-A*02:01-positive patients analyzed by performing major histocompatibility complex (MHC) class I tetramer enrichment. Two-thirds of these enriched HCV-specific CD8(+) T-cell populations displayed an effector memory phenotype, whereas, surprisingly, one-third displayed a naive-like phenotype despite ongoing viral replication.

Incomplete tumour control following DNA vaccination against rat gliomas expressing a model antigen.

Background: Vaccination against tumour-associated antigens is one approach to elicit anti-tumour responses. We investigated the effect of polynucleotide (DNA) vaccination using a model antigen (E. coli lacZ) in a syngeneic gliosarcoma model (9L).

gammadelta T-cells: basic features and potential role in vasculitis.

gammadelta T-cells are a numerically small subset of T-cells with distinct features. They recognise antigens that are not seen by other immune cells. At the functional level, gammadelta T-cells share some features with alphabeta T-cells but also exert functions that are otherwise performed by specialised subsets of alphabeta T-cells (e.

Increase in tumor size following intratumoral injection of immunostimulatory CpG-containing oligonucleotides in a rat glioma model.

The immunosuppressive environment of malignant gliomas is likely to suppress the anti-tumor activity of infiltrating microglial cells and lymphocytes. Macrophages and microglial cells may be activated by oligonucleotides containing unmethylated CpG-motifs, although their value in cancer immunotherapy has remained controversial. Following injection of CpG-containing oligonucleotides (ODN) into normal rat brain, we observed a local inflammatory response with CD8+ T cell infiltration, upregulation of MHC 2, and ED1 expression proving the immunogenic capacity of the CpG-ODN used.

Variant FCGR3 genes: transcription and possible origins.

The Fc receptors for human immunoglobulin G (FcgammaR) IIIb are encoded by genes clustered on the long arm of chromosome 1 (band q21 --> 24) and exhibit allelic polymorphisms. Several rare FCGR3B sequences were identified in both white and black donors. However, the origins of these genomic variants are unknown and their transcription has not yet been investigated.

HDR brachytherapy irradiation of the jaw - as a new experimental model of radiogenic bone damage.

Introduction: Hitherto, no suitable experimental model exists to test new treatments for radiogenic bone damage, such as new step from knowledge about bone growth factors or angiogenesis factors. The goal of this investigation was to establish such a standardised experimental model.

Material And Methods: Twenty-four rats were used in this study.

BMP-2 and bFGF in an irradiated bone model.

Introduction: Basic fibroblast growth factor (bFGF) is considered to enhance angiogenesis and to support bone formation in the presence of vital bone cells. Bone morphogenetic protein-2 (rhBMP-2) is known to induce bone formation. The aim of this study was to analyze the effect of bFGF and rhBMP-2 in the irradiated mandible.

Direct costimulatory effect of TLR3 ligand poly(I:C) on human gamma delta T lymphocytes.

TLR3 recognizes viral dsRNA and its synthetic mimetic polyinosinic-polycytidylic acid (poly(I:C)). TLR3 expression is commonly considered to be restricted to dendritic cells, NK cells, and fibroblasts. In this study we report that human gammadelta and alphabeta T lymphocytes also express TLR3, as shown by quantitative real-time PCR, flow cytometry, and confocal microscopy.