Frontiers in transplantation最新文献

It is increasingly appreciated that the expression of immunoregulatory molecules within tumors have potential to shape a microenvironment that promotes local immunoevasion and immunoregulation. However, little is known about tissue-intrinsic immunomodulatory mechanisms following transplantation. We propose that differences in the phenotype of microvascular endothelial cells impact the alloantigenicity of the graft and its potential to promote immunoregulation following transplantation. We focus this review on the concept that graft-dependent immunoregulation may evolve post-transplantation, and that it is dependent on the phenotype of select subsets of intragraft endothelial cells. We also discuss evidence that long-term graft survival is critically dependent on adaptive interactions among immune cells and endothelial cells within the transplanted tissue microenvironment.

More than a year after the Biological License Application (BLA) approval for CellTrans, cadaveric islet transplantation remains in demise in the United States (U.S.). While the therapy is unavailable to Americans, it is already a standard of care procedure in other countries, including Canada, Australia, and many in Europe. This article discusses the challenges stemming from an outdated regulatory framework in the U.S. concerning cadaveric islet transplantation. It also presents advocacy efforts by the transplant community for appropriate regulatory adjustments and discusses future perspectives.

Mass Spectrometry allied with in-vivo generation of activated alloreactive T cell populations and tetramer screening facilitates the identification of endogenous peptides that are directly recognised in complex with allogeneic Major Histocompatibility class I (MHC I) molecules by alloreactive CD8⁺ T cells. We had previously used this approach for the discovery of immunogenic self-peptides presented by the allomorph H-2K^b (K^b). In this study, we identified 22 highly immunogenic self-peptides presented by H-2K^d (K^d). Peptide abundance across skin, spleen and liver samples (estimated as the product of the spectral intensity obtained for these samples) was the principal factor influencing recognition of peptide-K^d epitopes. Predicted binding affinity (BA score) and overall peptide hydrophobicity were also independently correlated with immunogenicity, while there was no significant correlation between the IEDB immunogenicity score and the proportion of T cells recognising a given epitope. Eight peptide-K^d epitopes were selected for inclusion in a tetramer panel to detect directly alloreactive CD8⁺ T cells. This panel bound over 30% of activated alloreactive CD8⁺ T cells after a prime-boost against K^d. Moreover, the panel identified alloreactive CD8⁺ T cells within the graft infiltrate, spleen and draining lymph node during rejection of a K^d-bearing heart graft. In conclusion, small animal studies have demonstrated the feasibility of high-throughput approaches for the discovery of pMHC epitopes recognised by directly alloreactive T cells. Translating this approach to the human setting is achievable and will yield both critical insights into the fundamental basis of alloreactivity and powerful tools for immune monitoring in transplantation.

The Transplantation Society (TTS) has been presenting the Medawar Prize at its biennial Congresses since 1990 in recognition of Sir Peter Medawar's seminal contributions to organ transplantation. This prestigious award acknowledges individuals for their outstanding accomplishments in experimental and clinical transplantation. On September 25, 2024, I was honored to introduce Ronald W. Busuttil, M.D., Ph.D., as the 2024 Medawar Prize Laureate during the 30th TTS Congress in Istanbul, Turkey. This article highlights the remarkable achievements and critical milestones in Dr. Busuttil's over 40-year career in organ transplantation, which have profoundly advanced scientific knowledge and clinical practice, embodying the true spirit of this accolade.

This case report on recurrent urinary tract infections (UTIs) caused by multidrug-resistant (MDR) Klebsiella pneumoniae in a post-renal transplant patient underscores the significant clinical challenge of managing MDR infections in immunocompromised individuals, particularly in the context of renal transplantation. The patient was treated with an extended infusion of meropenem, which offers prolonged drug exposure and enhances bactericidal activity against MDR pathogens. This approach is critical in overcoming the resistance mechanisms inherent to Klebsiella pneumoniae, thereby improving the likelihood of therapeutic success. The findings presented here highlight the potential efficacy of extended meropenem infusion in treating MDR infections, providing a valuable therapeutic option for clinicians facing similar cases. This report contributes to the growing evidence supporting advanced antibiotic administration techniques in managing complicated urinary tract infections in transplant in resource limited countries.

Background: COVID-19 disease burden has been mitigated by vaccination; however, concerns persist regarding weakened immune responses in liver transplant (LT) recipients. This study investigates COVID-19 outcomes in LT recipients based on vaccination status.

Methods: This single-center retrospective study identified LT recipients with PCR-confirmed COVID-19 infection from 03/01/2020 to 07/31/2023. Logistic regression analyses were conducted, adjusting for age, race, co-morbidities, number of immunosuppressive agents, and infection date.

Results: Of 1,787 registered LT recipients, 361 had confirmed COVID-19 infection. Of those, 136 were unvaccinated and 225 were vaccinated. 13% had 1 vaccine dose, 31% had 2 vaccine doses, and 56% had 3 vaccine doses prior to infection. Logistic regression found higher mortality (p = 0.001) and hospitalization (p = 0.016) rates for older recipients, while those with 3 or more vaccine doses had lower mortality (p = 0.039) and hospitalization (p = 0.008) rates. Chronic kidney disease (CKD) increased risk of hospitalization (p < 0.001). Adjusting for the date when the Omicron variant became locally predominant, the protective effect from 3 or more vaccine doses declined to an OR (95% CI) of 0.58 (0.15-2.23), p = 0.39.

Conclusions: Three or more COVID-19 vaccine doses could decrease mortality for LT recipients, particularly older recipients and those with CKD. These individuals may benefit from vaccination and other interventions.

Introduction: The clinical characteristics of de novo inflammatory bowel disease (dnIBD) diagnosed after solid organ transplant (SOT) are not well-described, particularly since the advent of biologic therapy for treatment of IBD.

Methods: We conducted a single-center, retrospective review of SOT recipients between 2010 and 2022 at the University of Minnesota Medical Center who were diagnosed with IBD after transplant.

Results: Of 89 patients at our center with IBD and a history of SOT, five (5.6%) patients were diagnosed with IBD post-transplant (three liver, one kidney, and one simultaneous liver and kidney): three patients were female and four were Caucasian. Mean age at transplant and IBD diagnosis were 46.7 and 49.4 years respectively. Indication for transplant were alcohol-related cirrhosis (n = 2), idiopathic fulminant hepatic failure (n = 1), metabolic dysfunction-associated steatotic liver disease (n = 1), and IgA nephropathy (n = 1). Four patients were diagnosed with ulcerative colitis (UC) and one with Crohn's disease (CD). Three patients (all with UC) required escalation to a biologic therapy. Four patients were in clinical remission from IBD at last follow-up, one patient required IBD surgery, while there was no rejection and no deaths following IBD diagnosis.

Conclusion: dnIBD post-SOT is uncommon, while newer IBD therapies may be safe and effective. Further study is required to better understand the natural history and IBD outcomes of this population relative to non-SOT patients.

Vascularized composite allograft (VCA) transplantation represents a significant advancement in reconstructive surgery and offers hope to individuals who experienced congenital disorders or severe tissue injuries to restore physical appearance, function, and enhance quality of life. VCA recovery introduces complexities to conventional solid organ recovery, and there remain concerns regarding the potential impact of VCA recovery on non-VCA organs for transplant. The current retrospective study examines deceased donor characteristics and observed-to-expected (O/E) organ yield ratios for 51 VCA donors recovered in the US between July 4, 2014 and March 31, 2024, compared with a contemporary cohort of non-VCA donors recovered in 2023. Among the VCA donors, 17 donated a uterus, 15 each donated head and neck and upper limbs, 4 were abdominal wall donors, and 2 donated external male genitalia. The findings indicate that VCA donors tended to be younger (18-34 years old), predominantly White, non-Hispanic, and had no history of diabetes, along with lower weight, lower kidney donor profile index, and lower ejection fraction. The analysis revealed that VCA donors had higher observed overall organ yield than expected (O/E: 1.24, 95% CI: 1.16-1.33), with better-than-expected organ yields across VCA types. The number of deceased VCA donors in the US is still relatively small compared to the overall donor population. As the field continues to evolve and more data becomes available, further analyses need to be conducted to understand the demographics of VCA donors and the potential impact of VCA donation within the donation and transplant system.

Background and aims: There is growing interest in the environmental impact of surgical procedures, yet more information is needed specifically regarding liver transplantation. This study aims to quantify the total greenhouse gas emissions, or carbon footprint, associated with adult whole-size liver transplantation from donors after brain death, including the relevant back-table graft preparation.

Methods: The carbon footprint was calculated retrospectively using a bottom-up approach. This approach sums the volumes of energy consumption (kWh), volatile anesthetics (ml), solid waste (kg), and units of blood products transfused for each transplant. These consumption values were converted using validated conversion factors to the equivalent mass of carbon dioxide released into the environment (kg CO2e).

Results: A total of 147 patients with a mean age of 55 years (male, 78.9%) who underwent liver transplants between 2021 and 2022 were analyzed, resulting in 45.5 tons CO2e. The mean (SD) carbon footprint for each procedure was 309.8 (33.2) kg CO2e [95% CI: 304.4; 315.3]. Total energy power consumption was 96.5 MW, contributing 65.4% of greenhouse emissions (29.8 tons CO2e), while volatile anesthetics, solid waste, and blood product transfusions contributed 8.0% (3.64 tons CO2e), 5.9% (2.7 tons CO2e), and 20.6% (9.4 tons CO2e), respectively. The duration of surgery (t = 29.0; p < 0.001), transfused red blood cells (t = 13.1; p < 0.001), fresh frozen plasma (t = 11.1; p < 0.001), platelets (t = 8.9; p < 0.001), and the use of an extracorporeal pump machine (t = 3.6; p < 0.001) had the greatest effects on greenhouse gas emissions.

Conclusions: Liver transplantation requires significant energy and is associated with considerable greenhouse gas emissions, particularly during longer procedures. Transplant clinicians, hospital administrators, policymakers, and patients should be aware of the environmental impact of liver transplantation and collaborate to adopt sustainable energy practices.

The acute rejection (AR) diagnosis depends on transbronchial biopsy, which is semi-invasive and not easily performed. Our study used the Nanostring gene expression technology on PBMCs obtained from lung transplant recipients (LTRs) to search for biomarkers. We identified distinct differential gene profiles between patients with stable status (STA) and AR. Subsequently, we independently evaluated monocyte compositions in PBMCs using flow cytometry and assessed the levels of 7 chemokines in serum using Luminex. The 48 top differentially expressed genes (DEGs) were identified, utilizing a criterion of at least a 1.5-fold change between two groups, with a false discovery rate (FDR) p-Adj < 0.05. Of these 48 genes, the top 10 genes with the highest fold changes and significant p-values were selected for qPCR validation. CD68, ANXA1, ITGB, and IFI30 can be confirmed among the validated genes. A significantly lower percentage of CD14 + CD16- classical monocytes was observed in AR than in STA patients, which aligns with downregulated DEGs. Many of the DEGs were related to monocytes-macrophages and chemokines. Although these results still need to be confirmed in larger cohorts, they suggest that gene profiling of PBMC can help to identify markers related to AR in LTRs.