Prevention of allograft rejection often requires lifelong immune suppression, risking broad impairment of host immunity. Nonselective inhibition of host T cell function increases recipient risk of opportunistic infections and secondary malignancies. Here we demonstrate that AJI-100, a dual inhibitor of JAK2 and Aurora kinase A, ameliorates skin graft rejection by human T cells and provides durable

Vaccine-induced immune thrombosis and thrombocytopenia (VITT) syndrome is a new entity, characterised by severe thrombocytopenia and multiple sites of thrombosis1. The presumed mechanism is driven by anti-platelet factor 4 (PF4) antibodies causing platelet activation1. Donors with VITT syndrome have a particular relevance for liver transplantation (LT), due to the associated risk of passenger lymphocyte

Long-term survival after lung transplantation is limited by chronic allograft dysfunction. The aim of this study was to investigate the effect of locally augmented immunosuppression with liposomal cyclosporine A for inhalation (L-CsA-i) for the prevention of bronchiolitis obliterans syndrome (BOS). In a randomized, double-blind, placebo-controlled, multi-center Phase 3 study, 180 LT recipients in BOS

Obesity initiates a chronic inflammatory network linked to perioperative complications and increased acute rejection rates in organ transplantation. Bariatric surgery is the most effective treatment of obesity recommended for morbidly obese transplant recipients. Here, we delineated the effects of obesity and bariatric surgery on alloimmunity and transplant outcomes in diet-induced obese (DIO) mice

Hispanic patients receive disproportionately fewer living donor kidney transplants (LDKTs) than non-Hispanic Whites (NHWs). The Northwestern Medicine Hispanic Kidney Transplant Program (HKTP), designed to increase Hispanic LDKTs, was evaluated as a nonrandomized, implementation-effectiveness hybrid trial of patients initiating transplant evaluation at two intervention and two similar control sites

Despite decennia of research and numerous successful interventions in the preclinical setting, renal ischemia reperfusion (IR) injury remains a major problem in clinical practice, pointing towards a translational gap. Recently, two clinical studies on renal IR injury (manifested either as acute kidney injury or as delayed graft function), identified metabolic derailment as a key driver of renal IR

Immunogenicity following inactivated SARS-CoV-2 vaccination among solid organ transplant recipients has not been assessed. Seventy-five patients (37 kidney transplant [KT] recipients and 38 healthy controls) received two doses, at 4-week intervals, of an inactivated whole-virus SARS-CoV-2 vaccine. SARS-CoV-2-specific humoral (HMI) and cell-mediated immunity (CMI) were measured before, 4 weeks post-first

T cells must be activated and become effectors first before executing allograft rejection, a process that is regulated by diverse signals and transcription factors. In this study, we studied the basic leucine zipper ATF-like transcription factor (BATF) family members in regulating T cell activities in a heart transplant model and found that mice deficient for both BATF and BATF3 (Batf−/−Batf3−/− mice)

Our understanding of the involvement of the gut microbiota (GM) in human health has expanded exponentially over the last few decades, particularly in the fields of metabolism, inflammation, and immunology. Immunosuppressive treatment (IST) prescribed to solid organ transplant (SOT) recipients produces GM changes that affect these different processes. This review aims at describing the current knowledge

The probability of kidney transplantation for waitlisted candidates varies widely in the United States. The 3-year probability of deceased donor transplantation ranges from 4% to 64.2% - representing a 16 fold variation.(1) This variation is often attributed to geographical differences in the underlying organ supply but may be explained even more by the willingness of transplant programs to accept

While older males are at highest risk for poor COVID-19 outcomes, it is not known if this applies to the immunosuppressed recipient of a solid organ transplant (SOT), nor how the type of allograft transplanted may impact outcomes. In a cohort study of adult (>18 years) patients testing positive for COVID-19 (Jan 01, 2020-June 21, 2021) from 56 sites across the United States identified using the National

Hyperlipidemia induces accelerated rejection of cardiac allografts and resistance to tolerance induction using costimulatory molecule blockade in mice due in part to anti-donor Th17 responses and reduced regulatory T cell function. Accelerated rejection in hyperlipidemic mice is also associated with increased serum levels of IL-6. Here, we examined the role of IL-6 in hyperlipidemia-induced accelerated

On the cover: Over the past decade, tremendous progress in basic science arenas, including cell biology and bioengineering, coupled with wide-ranging technological advances from gene editing to normothermic perfusion platforms have exploded the horizon of opportunity for cellular therapies. Parsons et al. (page 3225) paint the current landscape. They begin with familiar applications of islet and hepatocyte

This month's installment of “The AJT Report” explores the challenge of sex disparity in transplant and what might be done to address this ongoing problem. We also report on a recent amendment to the U.S. Food and Drug Administration’s COVID-19 vaccine emergency use authorizations that affects solid organ recipients.

B cells infiltrating kidney allografts express a transcriptional program of innate inflammatory cells and are not selected for allospecificity.

More than one rational approach may address sex disparity in liver transplantation—now is the time for leadership and action rather than more analyses. Wood et al.'s article is on page 3296.

This editorial comments on a landmark case of single-stage long segment tracheal transplantation (Genden et al., page 3421).

Pregnant women with influenza-A have an increased risk of developing acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) can be used as salvage therapy, with lung transplantation as a therapeutic option. However, successful bilateral lung transplantation during pregnancy has never been reported before. We herein report the case of a 34-year-old primipara, who was

Summary What is already known about this topic? Nonpharmaceutical interventions introduced to mitigate the impact of COVID-19 reduced transmission of common respiratory viruses in the United States. What is added by this report? Influenza viruses and human metapneumovirus circulated at historic lows through May 2021. In April 2021, respiratory syncytial virus activity increased. Common human coronaviruses

Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020–June 19, 2020) and late 2020 (June 20, 2020–December 31, 2020). Multivariable logistic

Studies are urgently needed to characterize immunogenicity, efficacy, and safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in kidney transplant (KT) recipients, excluded from major clinical trials. Complex ELISPOT and other cellular response techniques have been applied, but simpler tools are needed. An easy-to-use real-world monitoring of SARS-CoV-2 IgG antibodies

I have read the manuscript entitled “Pure laparoscopic living donor liver transplantation: Dreams come true”,1 and I congratulate the authors. However, I think that some points must be clarified. The Oxford dictionary defines “dream”, as “… a wish to have or be something, especially one that seems difficult to achieve.” Is “Pure laparoscopic living donor liver transplantation” a dream? In my opinion

Kidney transplantation (KT) from deceased donors with hepatitis C virus (HCV) into HCV-negative recipients has become more common. However, the risk of complications such as BK polyomavirus (BKPyV) remains unknown. We assembled a retrospective cohort at four centers. We matched recipients of HCV-viremic kidneys to highly similar recipients of HCV-aviremic kidneys on established risk factors for BKPyV

Relevant concerns are being raised regarding the weak serological response of solid organ transplant (SOT) recipients after receiving two doses of messenger RNA-based vaccine against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1 and some severe cases of coronavirus disease (COVID-19) occurring after vaccination.2 Thus, additional preventive booster doses are proposed to enhance

Knowledge of living donor liver transplantation (LDLT) for autoimmune liver diseases (AILDs) is scarce. This study analyzed survival in LDLT recipients registered in the European Liver Transplant Registry with autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis (PSC) and the non-autoimmune disorder alcohol-related cirrhosis.

We conducted a randomized, placebo-controlled, double-blind study of pediatric lung transplant recipients, hypothesizing that rituximab plus rabbit anti-thymocyte globulin induction would reduce de novo donor-specific human leukocyte antigen antibodies (DSA) development and improve outcomes. We serially obtained clinical data, blood, and respiratory samples for at least one year post transplant. We

A number of studies have emphasized the weak humoral response to COVID-19 m-RNA vaccination in hemodialysis patients and kidney transplant recipients naïve to SARS-CoV-2.1, 2 Firket et al.3 recently reported in this journal that kidney transplant recipients previously infected with SARS-CoV-2 develop similar levels of anti-S1/S2 IgG titers compared with healthy controls following of BNT162b2 mRNA vaccination

While many adult solid organ transplant recipients (SOTRs) have impaired antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, pediatric SOTRs’ response has not been assessed.1, 2 We report the immunogenicity and safety of BNT162b2 mRNA vaccination in pediatric SOTRs.

Nearly 20 years ago, the implementation of the Model for End Stage Liver Disease (MELD) score was anticipated to reduce disparities in liver transplantation (LT). Prior to its rollout, Black patients with liver disease were noted to have lower listing rates and higher waitlist mortality compared to White patients.1, 2 While initial analysis did support that a transition to a MELD-based organ allocation

To meet new Centers for Medicare and Medicaid Services (CMS) metrics, organ procurement organizations (OPOs) will benefit from understanding performance across decedent and hospital types. We sought to determine the utility of existing data-reporting structures for this purpose by reviewing Scientific Registry of Transplant Recipient (SRTR) OPO-Specific Reports (OSRs) from 2013 to 2019. OSRs contain

Organ transplant recipients may not mount an adequate immune response to COVID-19 infection and therefore may benefit greatly from passive immunization with anti-spike monoclonal antibodies (mAbs), which have been shown to decrease hospitalization rates in the general outpatient population. We evaluated the efficacy of mAb therapy in decreasing hospitalizations or emergency room (ER) visits among kidney

Opportunities continue to be lost with a high rate of kidneys recovered for transplant but not utilized, particularly those considered less than ideal quality. The Organ Procurement and Transplant Network (OPTN) Organ Center is tasked with allocating arguably the most difficult-to-place kidneys, and we hypothesized an accelerated placement pathway would increase utilization of kidneys placed by the

The potential of adoptive cell therapy with regulatory T cells (Tregs) to promote transplant tolerance is under active exploration. However, the impact of specific transplant settings and protocols on Treg manufacturing is not well-delineated. Here, we compared the use of peripheral blood mononuclear cells (PBMCs) from patients before or after liver transplantation to the use of healthy control PBMCs

Donor-derived cell-free DNA (dd-cfDNA) has been evaluated as a rejection marker in organ transplantation. This study sought to assess the utility of dd-cfDNA to diagnose graft injury in liver transplant recipients (LTR) and as a predictive biomarker prior to different causes of graft dysfunction. Plasma from single and multicenter LTR cohorts was analyzed for dd-cfDNA. Phenotypes of treated biopsy-proven

Kidney transplant recipients (KTRs) are extremely vulnerable to SARS-CoV-2 infection and show an impaired immune response to SARS-CoV-2 vaccination. We analyzed factors related to vaccination efficiency in KTRs. In a multicenter prospective observational study (NCT04743947), IgG antibodies levels against SARS-CoV-2 spike S1 subunit and their neutralization capacity after SARS-CoV-2 vaccination were

Belatacept was developed to replace calcineurin inhibitors in kidney transplantation. Its use is associated with better kidney transplant function, a lower incidence of anti-donor antibodies and higher graft survival. However, it is also associated with a higher risk of cellular rejection. We studied the activation and proliferation mechanisms of belatacept-resistant T lymphocytes (TLs), to identify

In the current issue of AJT, Suh et al. report the first case of pure laparoscopic living donor liver transplantation, including native liver explantation and graft implantation.1 The procedure was successful with both donor (graft also procured by a pure laparoscopic approach of course) and recipient discharged without early complications. Liver transplantation, considered the ultimate limit to minimally

Recently, Dr. Kyung-Suk Suh and colleagues1 reported pure laparoscopic living donor liver transplantation, which raised great interest. Both explant hepatectomy and implantation of a modified graft were performed by laparoscopy for a 60-year-old recipient with alcoholic cirrhosis and hepatocellular carcinoma. This epoch-making work was the world's first liver transplantation (LT) totally accomplished

Food-safety measures are recommended to solid organ transplant (SOT) recipients. However, the burden of foodborne infections in SOT recipients has not been established. We describe the epidemiology and outcomes of bacterial foodborne infections in a nationwide cohort including 4405 SOT recipients in Switzerland between 2008 and 2018. Participants were prospectively followed for a median of 4.2 years

Galactosyl transferase knock-out pig lungs fail rapidly in baboons. Based on previously identified lung xenograft injury mechanisms, additional expression of human complement and coagulation pathway regulatory proteins, anti-inflammatory enzymes and self-recognition receptors, and knock-down of the β4Gal xenoantigen were tested in various combinations. Transient life-supporting GalTKO.hCD46 lung function

Immune responses reflect a complex interplay of cellular and extracellular components which define the microenvironment of a tissue. Therefore, factors that locally influence the microenvironment and re-establish tolerance might be beneficial to mitigate immune-mediated reactions, including the rejection of a transplant. In this study, we demonstrate that pre-incubation of donor tissue with the immune

Unlike immunocompetent hosts, the duration of viral persistence after infection with severe acute respiratory syndrome coronavirus 2 can be prolonged in immunosuppressed patients. Here, we present a case of viral persistence for over 19 weeks in a patient with a history of solid organ transplant and explore the clinical, virologic, and immunologic course. Our patient still demonstrated viral persistence

The SARS-CoV-2 pandemic has upended the world and the field of transplantation. With the introduction of COVID-19 vaccines, we have entered a new phase; however, our understanding of vaccine responses and protection against infection in solid organ transplant recipients continue to evolve. The current manuscript from Herrera et al. provides new insight into mRNA vaccine immune responses to mRNA-1273

Persistent interest in controlled donation after circulatory death (cDCD) liver transplantation exists due to supply-demand discrepancy for liver allografts. In the United States, over 2000 patients die or become too sick while awaiting liver transplant annually. cDCD liver transplantation has increased the source of donor organs; however, is associated with higher risk of primary non-function (PNF)

Donor/recipient incompatibility in kidney transplantation classically refers to ABO/HLA-incompatibility. Kidney paired donation (KPD) was historically established to circumvent ABO/HLA-incompatibility, with the goal of identifying ABO/HLA-compatible matches. However, there is a broad range of donor factors known to impact recipient outcomes beyond ABO/HLA-incompatibility, such as age and weight, and

This study assessed the impact of cancer on the risk of death with a functioning graft of kidney transplant (KT) recipients, as compared to corresponding recipients without cancer. A matched cohort study was conducted using data from a cohort of 13 245 individuals who had undergone KT in 17 Italian centers (1997–2017). Cases were defined as subjects diagnosed with any cancer after KT. For each case

Healthcare systems worldwide were challenged during the COVID-19 pandemic. In Mexico, the public hospitals that perform most transplants were adapted to provide care for COVID-19 patients. Using a nationwide database, we describe the first report of the impact of COVID-19 and related transplantation healthcare policies in a middle-income country by comparing statistics before and during the pandemic

Status 1A liver transplant candidates are given the highest medical priority for the allocation of deceased donor livers. Organ Procurement and Transplantation Network (OPTN) policy requires physicians to certify that a candidate has a life expectancy without a transplant of less than 7 days for that candidate to be given status 1A. Additionally, candidates receiving status 1A must have one of six

Graft survival beyond year 1 has not changed after orthotopic liver transplantation (OLT) over the last decades. Likewise, OLT causes comorbidities such as infection, renal impairment and cancer. We evaluated our single-center real-world individualized immunosuppression program after OLT, based on 211 baseline surveillance biopsies (svLbx) without any procedural complications. Patients were classified

The IgG-degrading enzyme derived from Streptococcus pyogenes (Imlifidase, Hansa Biopharma) is a novel agent that cleaves all four human subclasses of IgG and has therapeutic potential for HLA desensitization in kidney transplantation and antibody-mediated rejection. Data from clinical trials in kidney transplantation demonstrated rapid degradation of anti-HLA donor-specific antibodies facilitating

COVID-19 pandemic dramatically impacted transplantation landscape. Scientific societies recommend against the use of donors with active SARS-CoV-2 infection. Italian Transplant Authority recommended to test recipients/donors for SARS-CoV-2-RNA immediately before liver transplant (LT) and, starting from November 2020, grafts from deceased donors with active SARS-CoV-2 infection were allowed to be considered

Graft-versus-host disease (GVHD) after liver transplantation (LT) is a rare but horrific scenario. While it is far less common than steroid-refractory GVHD (SR-GVHD) seen after allogeneic hematopoietic stem cell transplantation (allo-HSCT), GVHD after LT is more ferocious and lethal. Even after the introduction of targeted biologicals that suppress signaling by certain pro-inflammatory cytokines such

Despite prevention strategies, cytomegalovirus (CMV) remains a common infection in pediatric solid organ transplant recipients (SOTR). We sought to determine the frequency, associations with, and long-term outcomes of CMV DNAemia in pediatric SOTR. We performed a single-center retrospective cohort study, including 687 first time SOTR ≤21 years receiving universal prophylaxis from 2011 to 2018. Overall

Poor responses to mRNA COVID-19 vaccine have been reported after 2 vaccine injections in kidney transplant recipients (KTRs) treated with belatacept. We analyzed the humoral response in belatacept-treated KTRs without a history of SARS-CoV-2 infection who received three injections of BNT162b2-mRNA COVID-19 vaccine. We also investigated vaccine immunogenicity in belatacept-treated KTRs with prior COVID-19

Niemann-Pick type C disease is a rare autosomal recessive lysosomal disorder that leads to the accumulation of lipids in cellular organelles. Affected infants are often cholestatic with hepatosplenomegaly, developmental delay and may present in acute liver failure. Medical therapy has shown some promise in long-term studies, in patients with milder phenotypes of the disease. Liver transplantation has

Increasing numbers of compatible pairs are choosing to enter paired exchange programs, but motivations, outcomes, and system-level effects of participation are not well described. Using a linkage of the Scientific Registry of Transplant Recipients and National Kidney Registry, we compared outcomes of traditional (originally incompatible) recipients to originally compatible recipients using the Kaplan–Meier

Coronavirus disease-19 (COVID-19) infection causing severe gastrointestinal complications is rare. A 9-year-old child after recovering from mild COVID-19 infection developed small bowel gangrene due to superior mesenteric artery thrombosis. He required resection of entire necrotic small bowel along with caecum causing ultra-short bowel syndrome. Reverse transcriptase-polymerase chain reaction (RT-PCR)

We have read the article written by Ison et al.1 that has raised some issues we would like to discuss. COVID-19 breakthrough infection rates in vaccinated kidney transplant (KT) recipients much higher than in the general vaccinated population have been reported.2 Furthermore, the severity remains markedly high. Although Ison et al. referred cases are rarely severe, other series, and among them, the

Lung transplantation with lungs procured from donors after circulatory death (DCD) has been established as an alternative technique to traditional donation after brain death (DBD) with comparable outcomes. Recently, in situ thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as a novel technique employed in the procurement of cardiac allografts after circulatory death. TA-NRP, in