The concept of immunothrombosis in pancreas transplantation.

Early failure of a pancreatic allograft due to complete thrombosis has an incidence of approximately 10% and is the main cause of comorbidity in pancreas transplantation. Although several risk factors have been identified, the exact mechanisms leading to this serious complication are still unclear. In this review, we define the roles of the individual components involved during sterile immunothrombosis-namely endothelial cells, platelets, and innate immune cells.

Corneal Graft Rejection: Is it Reflected in Peripheral Immune Cells? Results of a Prospective Multicenter Study (VISICORT).

Background: Allogeneic graft rejection is the leading cause of graft failure in corneal transplantation (CT) despite the immune privilege of the anterior chamber and corneal bed. The ability to identify patients at higher risk of acute rejection before or after CT could have a major impact on the clinical management of these patients.

Methods: To address this important issue, a multicenter European cohort of low-risk (n = 142) and high-risk (n = 102) CT recipients was established, and the immune system was evaluated in detail in peripheral blood mononuclear cells and plasma before and 6 and 12 mo posttransplantation.

Rise of a CD27 IgD CD11c B cells population in kidney recipients achieving long-term graft stability under immunosuppression.

The use of immunosuppressive treatment is required to prevent rejection events, even a long time after kidney transplantation despite rare recipients achieving long-term graft stability without the need for immunosuppressive treatment, called operationally tolerant patients (TOLs). We comprehensively investigate the immune system of long-term IS recipients (LTTs) and TOLs to highlight their shared and unique immune features. Blood immune cell phenotyping was performed by spectral cytometry.

Microvascular Inflammation of Kidney Allografts and Clinical Outcomes.

Background: The heterogeneous clinical presentation of graft microvascular inflammation poses a major challenge to successful kidney transplantation. The effect of microvascular inflammation on allograft outcomes is unclear.

Methods: We conducted a cohort study that included kidney-transplant recipients from more than 30 transplantation centers in Europe and North America who had undergone allograft biopsy between 2004 and 2023.

Archetypal Analysis of Kidney Allograft Biopsies Using Next-generation Sequencing Technology.

Background: In kidney transplantation, molecular diagnostics may be a valuable approach to improve the precision of the diagnosis. Using next-generation sequencing (NGS), we aimed to identify clinically relevant archetypes.

Methods: We conducted an Illumina bulk RNA sequencing on 770 kidney biopsies (540 kidney recipients) collected between 2006 and 2021 from 11 European centers.

Evaluation of non-invasive biomarkers of kidney allograft rejection in a prospective multicenter unselected cohort study (EU-TRAIN).

Non-invasive biomarkers are promising tools for improving kidney allograft rejection monitoring, but their clinical adoption requires more evidence in specifically designed studies. To address this unmet need, we designed the EU-TRAIN study, a large prospective multicentric unselected cohort funded by the European Commission. Here, we included consecutive adult patients who received a kidney allograft in nine European transplant centers between November 2018 and June 2020.

Regulatory B Cells Expressing Granzyme B from Tolerant Renal Transplant Patients: Highly Differentiated B Cells with a Unique Pathway with a Specific Regulatory Profile and Strong Interactions with Immune System Cells.

The aim of our study was to determine whether granzyme B-expressing regulatory B cells (GZMB B cells) are enriched in the blood of transplant patients with renal graft tolerance. To achieve this goal, we analysed two single-cell RNA sequencing (scRNAseq) datasets: (1) peripheral blood mononuclear cells (PBMCs), including GZMB B cells from renal transplant patients, i.e.

Blood Gene Signature as a Biomarker for Subclinical Kidney Allograft Rejection: Where Are We?

The observation decades ago that inflammatory injuries because of an alloimmune response might be present even in the absence of concomitant clinical impairment in allograft function conduced to the later definition of subclinical rejection. Many studies have investigated the different subclinical rejections defined according to the Banff classification (subclinical T cell-mediated rejection and antibody-mediated rejection), overall concluding that these episodes worsened long-term allograft function and survival. These observations led several transplant teams to perform systematic protocolar biopsies to anticipate treatment of rejection episodes and possibly prevent allograft loss.

Fine-tuning tumor- and allo-immunity: advances in the use of immune checkpoint inhibitors in kidney transplant recipients.

Cancer is a common complication after kidney transplantation. Kidney transplant recipients (KTR) have a 2- to 4-fold higher risk of developing cancer compared to the general population and post-transplant malignancy is the third most common cause of death in KTR. Moreover, it is well known that certain cancer types are overrepresented after transplantation, especially non-melanoma skin cancer.

Blood MMP-9 measured at 2 years after lung transplantation as a prognostic biomarker of chronic lung allograft dysfunction.

Background: Long-term outcomes of lung transplantation (LTx) remain hampered by chronic lung allograft dysfunction (CLAD). Matrix metalloproteinase 9 (MMP-9) is a secretory endopeptidase identified as a key mediator in fibrosis processes associated with CLAD. The objective of this study was to investigate whether plasma MMP9 levels may be prognostic of CLAD development.

Polyclonal antibodies selectively inhibit tumor growth and invasion and synergize with immune checkpoint inhibitors.

Heterologous polyclonal antibodies (pAb) were shown to possess oncolytic properties a century ago with reported clinical responses. More recent preclinical models confirmed pAb efficacy, though their ability to tackle complex target antigens reduces susceptibility to tumor escape. Owing to the recent availability of glyco-humanized pAb (GH-pAb) with acceptable clinical toxicology profile, we revisited use of pAb in oncology and highlighted their therapeutic potential against multiple cancer types.

Addressing vaccine hesitancy: experimental evidence from nine high-income countries during the COVID-19 pandemic.

We study the impact of public health messages on intentions to vaccinate and vaccination uptakes, especially among hesitant groups. We performed an experiment comparing the effects of egoistic and altruistic messages on COVID-19 vaccine intentions and behaviour. We administered different messages at random in a survey of 6379 adults in December 2020, following up with participants in the nationally representative survey Citizens' Attitudes Under COVID-19 Project covering nine high-income countries (Australia, Austria, France, Germany, Italy, New Zealand, Sweden, the UK and the USA).

Pre-transplant immune profile defined by principal component analysis predicts acute rejection after kidney transplantation.

Background: Acute rejection persists as a frequent complication after kidney transplantation. Defining an at-risk immune profile would allow better preventive approaches.

Methods: We performed unsupervised hierarchical clustering analysis on pre-transplant immunological phenotype in 1113 renal transplant recipients from the ORLY-EST cohort.

An exome-wide study of renal operational tolerance.

Background: Renal operational tolerance is a rare and beneficial state of prolonged renal allograft function in the absence of immunosuppression. The underlying mechanisms are unknown. We hypothesized that tolerance might be driven by inherited protein coding genetic variants with large effect, at least in some patients.

Immunosuppressant drugs and quality-of-life outcomes in kidney transplant recipients: An international cohort study (EU-TRAIN).

Patient-Reported Outcomes (PRO) integrate a wide range of holistic dimensions that arenot captured within clinical outcomes. Particularly, from induction treatment to maintenance therapy, patient quality-of-life (QoL) of kidney transplant recipients have been sparsely investigated in international settings. In a prospective, multi-centric cohort study, including nine transplant centers in four countries, we explored the QoL during the year following transplantation using validated elicitation instruments (EQ-5D-3L index with VAS) in a population of kidney transplant patients receiving immunosuppressive therapies.

Kidney allograft rejection is associated with an imbalance of B cells, regulatory T cells and differentiated CD28-CD8+ T cells: analysis of a cohort of 1095 graft biopsies.

Introduction: The human immune system contains cells with either effector/memory or regulatory functions. Besides the well-established CD4+CD25hiCD127lo regulatory T cells (Tregs), we and others have shown that B cells can also have regulatory functions since their frequency and number are increased in kidney graft tolerance and B cell depletion as induction therapy may lead to acute rejection. On the other hand, we have shown that CD28-CD8+ T cells represent a subpopulation with potent effector/memory functions.

An automated histological classification system for precision diagnostics of kidney allografts.

For three decades, the international Banff classification has been the gold standard for kidney allograft rejection diagnosis, but this system has become complex over time with the integration of multimodal data and rules, leading to misclassifications that can have deleterious therapeutic consequences for patients. To improve diagnosis, we developed a decision-support system, based on an algorithm covering all classification rules and diagnostic scenarios, that automatically assigns kidney allograft diagnoses. We then tested its ability to reclassify rejection diagnoses for adult and pediatric kidney transplant recipients in three international multicentric cohorts and two large prospective clinical trials, including 4,409 biopsies from 3,054 patients (62.

Subclinical rejection-free diagnostic after kidney transplantation using blood gene expression.

We previously established a six-gene-based blood score associated with operational tolerance in kidney transplantation which was decreased in patients developing anti-HLA donor-specific antibodies (DSA). Herein, we aimed to confirm that this score is associated with immunological events and risk of rejection. We measured this using quantitative PCR (qPCR) and NanoString methods from an independent multicenter cohort of 588 kidney transplant recipients with paired blood samples and biopsies at one year after transplantation validating its association with pre-existing and de novo DSA.

Regulation of CD8 T cell by B-cells: A narrative review.

Activation of CD4 T cells by B cells has been extensively studied, but B cell-regulated priming, proliferation, and survival of CD8 T cells remains controversial. B cells express high levels of MHC class I molecules and can potentially act as antigen-presenting cells (APCs) for CD8 T cells. Several studies in mice and humans demonstrate the role of B cells as modulators of CD8 T cell function in the context of viral infections, autoimmune diseases, cancer and allograft rejection.