Safety and Immunogenicity of SARS-CoV-2 mRNA Vaccine Booster Doses in Kidney Transplant Recipients: Results of a 12-mo Follow-up From a Prospective Observational Study.

Background: Booster doses of SARS-CoV-2 mRNA vaccines are commonly used in kidney transplant recipients (KTRs). However, there is uncertainty regarding the waning of vaccination responses and immunological safety in KTRs.

Methods: A total of 123 KTRs were included in the final analysis of this prospective observational cohort study.

Effect of SARS-CoV-2 infection on anti-HLA antibodies and de novo donor specific antibodies incidence in lung transplant recipients.

Purpose: There are no clear guidelines on how to handle immunosuppression in lung transplant recipients (LTRs) infected by SARS-CoV-2. Antimetabolite reduction with corticosteroid escalation is the most frequent strategy. The aim of this study was to determine the effect of this therapeutic approach on the incidence of de novo donor specific-antibodies (dnDSA).

haplotype is associated with poor graft survival in kidney transplant recipients with thrombotic microangiopathy.

thrombotic microangiopathy (TMA) is associated with poor kidney graft survival, and as we previously described, it is a recipient driven process with suspected genetic background. Direct Sanger sequencing was performed in 90 KTR with TMA and 90 corresponding donors on selected regions in , and genes that involve variations with a functional effect or confer a risk for aHUS. Additionally, 37 recipients of paired kidneys who did not develop TMA were analyzed for the haplotype.

Predictive Potential of Flow Cytometry Crossmatching in Deceased Donor Kidney Transplant Recipients Subjected to Peritransplant Desensitization.

Recipient sensitization is a major risk factor of antibody-mediated rejection (ABMR) and inferior graft survival. The predictive effect of solid-phase human leukocyte antigen antibody testing and flow cytometry crossmatch (FCXM) in the era of peritransplant desensitization remains poorly understood. This observational retrospective single-center study with 108 donor-specific antibody (DSA)-positive deceased donor kidney allograft recipients who had undergone peritransplant desensitization aimed to analyze variables affecting graft outcome.

Intimal Arteritis and Microvascular Inflammation Are Associated With Inferior Kidney Graft Outcome, Regardless of Donor-Specific Antibodies.

The prognostic role of intimal arteritis of kidney allografts in donor-specific antibody negative (DSA-) antibody-mediated rejection (ABMR) remains unclear. Seventy-two out of 881 patients who had undergone kidney transplantation from 2014 to 2017 exhibited intimal arteritis in biopsies performed during the first 12 months. In 26 DSA negative cases, the intimal arteritis was accompanied by tubulointerstitial inflammation as part of T cell-mediated vascular rejection (TCMRV, = 26); intimal arteritis along with microvascular inflammation occurred in 29 DSA negative (ABMRV/DSA-) and 19 DSA positive cases (ABMRV, DSA+, = 17).

ELISpot assay and prediction of organ transplant rejection.

The ELISpot assay is a sensitive technique applied to assess cytokine-producing memory/effector T cells and human leukocyte antigens (HLA)-specific IgG-producing B cells. Besides the fact that the method is laborious and is difficult to standardise between laboratories, it may provide valuable information on the immune response of recipients before and after organ transplantation. In this article, we briefly review the recent literature and discuss the clinical significance of the ELISpot assay in predicting the risk and incidence of allograft rejection and survival.

Chronic Active Antibody-Mediated Rejection Is Associated With the Upregulation of Interstitial But Not Glomerular Transcripts.

Molecular assessment of renal allografts has already been suggested in antibody-mediated rejection (ABMR), but little is known about the gene transcript patterns in particular renal compartments. We used laser capture microdissection coupled with quantitative RT-PCR to distinguish the transcript patterns in the glomeruli and tubulointerstitium of kidney allografts in sensitized retransplant recipients at high risk of ABMR. The expressions of 13 genes were quantified in biopsies with acute active ABMR, chronic active ABMR, acute tubular necrosis (ATN), and normal findings.

Changes in phenotypic patterns of blood monocytes after kidney transplantation and during acute rejection.

Peripheral blood monocytes, which serve as precursors for tissue macrophages and dendritic cells (DC), play a key role in the immune response to kidney allograft, reparation processes and homeostasis regulation. In this prospective study, we used multicolor flow cytometry to monitor the phenotypic patterns of peripheral monocytes in subjects with uncomplicated outcomes and those with acute rejection. We found a reciprocal increase in the proportion of "classical monocytes" (CD14+CD16-) along with a decline in pro-inflammatory "intermediary" (CD14+CD16+) and "non-classical" (CD14lowCD16+) monocytes in subjects with normal outcomes.

Data and optimisation requirements for Kidney Exchange Programs.

Kidney Exchange Programs (KEP) are valuable tools to increase the options of living donor kidney transplantation for patients with end-stage kidney disease with an immunologically incompatible live donor. Maximising the benefits of a KEP requires an information system to manage data and to optimise transplants. The data input specifications of the systems that relate to key information on blood group and Human Leukocyte Antigen (HLA) types and HLA antibodies are crucial in order to maximise the number of identified matched pairs while minimising the risk of match failures due to unanticipated positive crossmatches.

A Europe wide acceptable mismatch program will enable transplantation of long waiting highly sensitised patients with a compatible donor.

Immunisation against Human Leucocyte Antigens (HLA) can be caused by pregnancy, blood transfusion, or organ transplants. The HLA antibody status of a given patient significantly influences their access and waiting time to transplant. For some highly sensitised patients (HSP) there is hardly any suitable donor available in the deceased donor pool of their allocation organisation and therefore they wait a very long time before being offered a kidney for transplant.

Donor specific anti-HLA antibodies and cardiac allograft vasculopathy: A prospective study using highly automated 3-D optical coherence tomography analysis.

Introduction: Recent studies suggested potential positive correlations between HLA-specific antibodies and development of cardiac allograft vasculopathy (CAV).

Methods: This prospective two-center study investigated early progression of CAV by coronary optical coherence tomography in 1 month and 12 months after heart transplantation (HTx) in 104 patients. Detection and characterization of donor specific (DSA) and MHC class-I polypeptide-related sequence A (MICA) antibodies were performed before, 1, 6 and 12 months after transplantation.

De novo HLA Class II antibodies are associated with the development of chronic but not acute antibody-mediated rejection after liver transplantation - a retrospective study.

Donor-specific antibodies (DSA) cause antibody-mediated rejection (AMR); however, their pathogenic role has not yet been adequately investigated after liver transplantation. The aim of our study was to analyse the clinical significance of DSA and complement-binding DSA for the prediction of AMR after liver transplantation. Our cohort included 120 liver recipients with assessed protocol biopsies one year post-transplant.

Crossing borders to facilitate live donor kidney transplantation: the Czech-Austrian kidney paired donation program - a retrospective study.

Kidney paired donation (KPD) is a valuable tool to overcome immunological barriers in living donor transplantation. While small national registries encounter difficulties in finding compatible matches, multi-national KPD may be a useful strategy to facilitate transplantation. The Czech (Prague) and Austrian (Vienna) KPD programs, both initiated in 2011, were merged in 2015.

Heterologous Cytomegalovirus and Allo-Reactivity by Shared T Cell Receptor Repertoire in Kidney Transplantation.

Cytomegalovirus (CMV) infection is associated with allograft rejection but the mechanisms behind are poorly defined yet. Although cross-reactivity of T cells to alloantigen and CMV has been hypothesized, direct evidence in patients is lacking. In this observational cohort study, we tested the pre-transplant effector/memory T cell response to CMV peptide pools and alloantigen in 78 living donor/recipient pairs using the interferon-gamma Enzyme-Linked ImmunoSpot (ELISPOT) assay.

Towards uniformity in the definition of acceptable mismatches for highly sensitized patients.

The Eurotransplant (The Eurotransplant International Foundation) acceptable mismatch programme has been shown to be a successful tool to enhance transplantation of highly sensitized patients(HSPs). However, patients with rare HLA phenotypes in relation to the Eurotransplant donor population remain on the waiting list. EUROSTAM is an European Union funded project to explore the feasibility of a Europe-wide acceptable mismatch programme enabling transplantation of HSPs with rare HLA phenotypes within their own organ exchange organization.

Risk of recurrence of primary sclerosing cholangitis after liver transplantation is associated with inflammatory bowel disease.

Aim: To evaluate risk factors for primary sclerosing cholangitis (PSC) recurrence (rPSC) after orthotopic liver transplantation (OLT) in patients with well-preserved colons.

Methods: We retrospectively evaluated the medical records of all patients transplanted for PSC in our center between July 1994 and May 2015 and selected 47 with follow-up of at least 60 mo for further analysis based on strict inclusion and exclusion criteria. rPSC was confirmed by magnetic resonance or endoscopic retrograde cholangiopancreatography and liver biopsy.

Efficacy and safety of BORTEZOMIB treatment for refractory acute antibody-mediated rejection-a pilot study.

A novel therapeutic approach to refractory acute antibody-mediated rejection (AMR) in kidney transplant recipients was applied in 23 patients based on administration of Bortezomib, intravenous corticosteroids, plasmapheresis and Rituximab. Application of Bortezomib regimen led to diminishing of donor-specific antibodies (DSA) to HLA-B (P = 0.004) and HLA-DR (P = 0.

Antibody-mediated rejection after liver transplantation-relevance of C1q and C3d-binding antibodies.

The aim of our study was to evaluate the relevance of complement-binding donor-specific antibodies (DSA) for prediction of antibody-mediated rejection (AMR) after liver transplantation. Sera from 123 liver transplant recipients were retrospectively defined for HLA specificity and complement-fixing activity using the single antigen beads, C1q and C3d techniques. Liver-recipients' sera were tested before transplantation, 3, 6 months and 1 year after transplantation.

The possible critical role of T-cell help in DSA-mediated graft loss.

In this review, we discuss a possible central role of T-cell help in severe forms of graft damage mediated by donor-specific HLA antibodies (DSA). Some kidney transplant recipients with pretransplant DSA show a high graft failure rate, whereas in other patients DSA do not harm the transplanted kidney and in most cases, disappear shortly after transplantation. Analyzing 80 desensitized highly immunized kidney transplant recipients and another multicenter cohort of 385 patients with pretransplant HLA antibodies, we reported recently that an ongoing T-cell help from an activated immune system, as measured by an increased level of soluble CD30 in serum, might be necessary for the DSA to exert a deleterious effect.

The effect of induction therapy on established CMV specific T cell immunity in living donor kidney transplantation.

Cytomegalovirus (CMV) infection influences both short and long term outcomes in immunosuppressed organ transplant recipients. The aim of this study was to evaluate the effect of different induction immunosuppression regimens on CMV specific T cell response in patients with already established CMV immunity. In 24 seropositive living donor kidney recipients, the frequency of CMV specific T cells was determined by ELISPOT (Enzyme-Linked ImmunoSpot) assay prior and 6 months after transplantation.