vascularized-composite-hand-allograft-procurement-preparation-for

Vascularized Composite Hand Allograft Procurement and Preparation for Distal and Proximal Forearm Allotransplantation: A Stepwise Approach

Upper limb amputations represent a real medical and surgical challenge. The ideal treatment should restore function, sensation, and body image. At ...

vascularized-composite-upper-limb-allograft-harvesting-for-proximal

Vascularized Composite Upper Limb Allograft Harvesting for Proximal Arm Allotransplantation

In vascularized composite allograft (VCA) for upper limb reconstruction, upper arm-level or transhumeral transplantations are performed less frequently ...

procurement-for-vascularized-reinnervated-abdominal-wall

Procurement for a Vascularized and Reinnervated Abdominal Wall Allotransplantation

Extensive and complex abdominal wall defects, particularly those associated with intestinal or visceral organ damage, pose significant medical and ...

an-experimental-human-diep-flap-model-to-investigate-preservation

An Experimental Human DIEP Flap Model to Investigate Preservation Strategies for Vascularized Composite Allografts and Free Flaps

Recently, preservation approaches such as cytoprotective agents injection, ex vivo machine perfusion, and supercooling have emerged as strategies to ...

University Côte d'Azur

University Hospital of Nice

University Côte d’Azur

Université Côte d'Azur, CNRS, LP2M

The immunogenicity of a two-dose mRNA COVID-19 vaccine regimen is low in kidney transplant (KT) recipients. Here, we provide a thorough assessment of the immunogenicity of a three-dose COVID-19 vaccine regimen in this population.

Safety and cross-variant immunogenicity of a three-dose COVID-19 mRNA vaccine regimen in kidney transplant recipients.

Preventing allograft rejection has been the main challenge of transplantation medicine since the discovery of immune responses against foreign HLA molecules in the mid-20th century. Prevention of rejection currently relies on immunosuppressive drugs, which lack antigen specificity and therefore increase the risk for infections and cancers. Adoptive cell therapy with donor-reactive regulatory T cells (Tregs) has progressively emerged as a promising approach to reduce the need for pan-immunosuppressive drugs and minimize morbidity and mortality in solid-organ transplant recipients. Chimeric antigen receptor (CAR) technology has recently been used successfully to generate Tregs specific for donor HLA molecules and overcome the limitations of Tregs enrichment protocols based on repetitive stimulations with alloantigens. While this novel approach opens new possibilities to make Tregs therapy more feasible, it also creates additional challenges. It is essential to determine which source of therapeutic Tregs, CAR constructs, target alloantigens, safety strategies, patients and immunosuppressive regimens are optimal for the success of CAR Treg therapy. Here, we discuss unmet needs and strategies to bring donor-specific CAR Treg therapy to the clinic and make it as accessible as possible.

Overcoming barriers to widespread use of CAR-Treg therapy in organ transplant recipients.

Kidney transplant (KT) recipients are at increased risk of developing severe forms of COVID-19. Little is known about the immunological mechanisms underlying disease severity in these patients receiving T-cell targeting immunosuppressive drugs. We investigated the relationship between T cell responsiveness at the beginning of the infection and the risk of subsequent progression to respiratory failure. We performed a multicentric prospective study in KT recipients with a positive RT-PCR COVID-19 test and only mild symptoms at inclusion. Blood samples were collected at baseline in a cell culture system containing T cell stimuli. We assessed T cell responsiveness by computing the ratio between the levels of Th1, Th2, Th17 and Treg cytokines produced after polyclonal stimulation and the number of blood lymphocytes. We then used an unsupervised classification approach to stratify patients into low and high T cell responders and a penalized logistic regression to evaluate the association between T cell responsiveness and progression to severe pneumonia. Forty-five patients were included. All patients who progressed to severe pneumonia (24.4%, n = 11) were low T cell responders at baseline ( = 0.01). In multivariate analysis, low T cell responsiveness at baseline was the main risk factor for subsequent progression to severe pneumonia. This study provides novel insights into the mechanisms underlying COVID-19 severity in organ transplant recipients and data of interest to clinicians managing immunosuppressive drugs in these patients.

Low T Cell Responsiveness in the Early Phase of COVID-19 Associates with Progression to Severe Pneumonia in Kidney Transplant Recipients.

Mucosal antibodies can prevent virus entry and replication in mucosal epithelial cells and therefore virus shedding. Parenteral booster injection of a vaccine against a mucosal pathogen promotes stronger mucosal immune responses following prior mucosal infection compared with injections of a parenteral vaccine in a mucosally naive subject. We investigated whether this was also the case for the BNT162b2 coronavirus disease 2019 (COVID-19) messenger RNA vaccine.

A Single Dose of BNT162b2 Messenger RNA Vaccine Induces Airway Immunity in Severe Acute Respiratory Syndrome Coronavirus 2 Naive and Recovered Coronavirus Disease 2019 Subjects.

Drug-Induced Tubulointerstitial Nephritis: Insights From the World Health Organization Safety Database.

Solid organ transplant recipients are at high risk for fatal forms of coronavirus disease 2019 (COVID-19). We conducted a cohort study among kidney transplant (KT) recipients from the French Solid Organ Transplant COVID-19 Registry to investigate the association between maintenance immunosuppressive drugs and 60-d mortality.

Association Between Maintenance Immunosuppressive Regimens and COVID-19 Mortality in Kidney Transplant Recipients.

Immune checkpoint inhibitors (ICIs) foster anti-cancer immune responses. Their efficacy comes at the cost of immune-related adverse events (IRAEs). The latter affects various organs, including kidneys, mostly as acute tubulointerstitial nephritis, the pathophysiology of which remains unclear. We conducted a multicentre case-control study to compare the characteristics of patients with renal IRAEs (ICI-AKI) with those of patients diagnosed with other IRAEs.

Risk factors associated with immune checkpoint inhibitor-induced acute kidney injury compared with other immune-related adverse events: a case-control study.

Chimeric antigen receptor T (CAR-T) cells have proven to be a game changer for treating several hematologic malignancies. Randomized controlled trials have highlighted potential life-threatening adverse drug reactions (ADRs), including cytokine release syndrome (CRS). Acute renal failure (ARF) has also been reported in 20% of the patients treated. However, an analysis of renal safety supported by large-scale real-life data seems warranted.

CAR-T Cells and the Kidney: Insights from the WHO Safety Database.

Membranous nephropathy can lead to end-stage kidney disease, for which kidney transplantation is the preferred therapy. However, the disease often relapses, which can impact allograft survival.

Anti Phospholipase A2 Receptor 1 Antibodies and Membranous Nephropathy Recurrence After Kidney Transplantation.

Transplant recipients face increased cancer mortality due to immunosuppressive treatments. Immune checkpoint inhibitors (ICI) have improved survival rates, but data on the use of these agents in transplant recipients is scarce. ICI may trigger allograft rejection, but the absolute risk of AR between the different ICI classes remains to be defined.

PDL1 inhibitors may be associated with a lower risk of allograft rejection than PD1 and CTLA4 inhibitors: analysis of the WHO pharmacovigilance database.

ArticleTotal : 4	Year
Publication title	2025
Publication title	2025
Publication title	2025
Publication title	2025

Article	Year
Safety and cross-variant immunogenicity of a three-dose COVID-19 mRNA vaccine regimen in kidney transplant recipients. EBioMedicine\| PubMed ID: 34763205	2021
Overcoming barriers to widespread use of CAR-Treg therapy in organ transplant recipients. HLA\| PubMed ID: 35233971	2022
Low T Cell Responsiveness in the Early Phase of COVID-19 Associates with Progression to Severe Pneumonia in Kidney Transplant Recipients. Viruses\| PubMed ID: 35336949	2022
A Single Dose of BNT162b2 Messenger RNA Vaccine Induces Airway Immunity in Severe Acute Respiratory Syndrome Coronavirus 2 Naive and Recovered Coronavirus Disease 2019 Subjects. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America\| PubMed ID: 35579991	2022
Drug-Induced Tubulointerstitial Nephritis: Insights From the World Health Organization Safety Database. Kidney international reports\| PubMed ID: 35812279	2022
Association Between Maintenance Immunosuppressive Regimens and COVID-19 Mortality in Kidney Transplant Recipients. Transplantation\| PubMed ID: 35883236	2022
Risk factors associated with immune checkpoint inhibitor-induced acute kidney injury compared with other immune-related adverse events: a case-control study. Clinical kidney journal\| PubMed ID: 36158153	2022
CAR-T Cells and the Kidney: Insights from the WHO Safety Database. BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy\| PubMed ID: 37166707	2023
Anti Phospholipase A2 Receptor 1 Antibodies and Membranous Nephropathy Recurrence After Kidney Transplantation. Kidney international reports\| PubMed ID: 39698349	2024
PDL1 inhibitors may be associated with a lower risk of allograft rejection than PD1 and CTLA4 inhibitors: analysis of the WHO pharmacovigilance database. Frontiers in immunology\| PubMed ID: 39911399	2025

Antoine Sicard

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