Transplant immunology最新文献

Tuberculosis (TB) infection in solid organ transplantation is a non-negligible problem in TB-endemic countries, and none of the existing guidelines recommend using organs from individuals with active TB infections. Here, we describe three cases of utilization of kidneys from TB-infected donors in renal transplantation at our center, two of whom had active TB. In these three cases, all recipients had good graft function and negative TST results during the 1-4 year follow-up period. This case report emphasizes the critical role of early diagnosis, prophylaxis and treatment of TB in renal transplantation, demonstrates the potential for utilizing kidneys from donors with active TB, and opens up a new possibilities for solid organ transplantation.

Objective: This study aimed to explore the clinical features, early diagnostic methods, and therapeutic approaches for invasive pulmonary aspergillosis (IPA) in patients after renal transplantation (RT).

Methods: We retrospectively examined 22 patients who were diagnosed with IPA post-RT and treated at our institution between 2005 and 2024.

Results: Patients had an average age of 46.4 ± 9.4 years, with a predominance of men (72.7 %). The incidence of IPA after RT was 1.29 %. The median time of IPA onset after transplantation was 12 months. Fever was the predominant symptom (72.7 %), followed by cough and expectoration (31.8 %) and hemoptysis (13.6 %). Frequent computed tomography findings included consolidations (68.2 %) and cavities (45.5 %) with halo signs, multiple nodules, and air crescent signs. Neutropenia was noted in five patients, including one case of agranulocytosis. Impaired renal function was observed in 59.1 % of the cases. Serum 1,3-β-D-glucan and galactomannan (GM) assays were positive in 45.5 % of patients, with bronchoalveolar lavage fluid GM tests confirming IPA in 83.3 % of those tested. Next-generation sequencing confirmed Aspergillus infection in 11 patients. Ultimately, 68.2 % of the patients recovered, whereas 31.8 % succumbed to the infection, with the deceased demonstrating a significantly high rate of complications.

Conclusions: Patients with IPA had high mortality rates. The symptoms of IPA after RT are usually nonspecific, making diagnosis very difficult. Bronchoalveolar lavage fluid GM testing and next-generation sequencing proved relatively helpful as detection methods for IPA. Antifungal treatments should be initiated as soon as possible to avoid complications.

Background: Ischemia-reperfusion injury (IRI) is an unavoidable consequence post-kidney transplantation, which inevitably leads to kidney damage. Numerous studies have demonstrated that mitophagy is implicated in human cancers. However, the function of mitophagy in kidney transplantation remains poorly understood. This study aims to develop mitophagy-related gene (MRGs) signatures to predict delayed graft function (DGF) and renal allograft loss post-kidney transplantation.

Methods: Differentially expressed genes (DEGs) were identified and intersected with the MRGs to obtain mitophagy-related DEGs (MRDEGs). Functional enrichment analyses were conducted. Subsequently, random forest and SVM-RFE machine learning were employed to identify hub genes. The DGF diagnostic prediction signature was constructed using LASSO regression analysis. The renal allograft prognostic prediction signature was developed through univariate Cox and LASSO regression analysis. In addition, ROC curves, immunological characterization, correlation analysis, and survival analysis were performed.

Results: Nineteen MRDEGs were obtained by intersecting 61 DEGs with 4897 MRGs. Seven hub genes were then identified through machine learning. Subsequently, a five-gene DGF diagnostic prediction signature was established, with ROC curves indicating its high diagnostic value for DGF. Immune infiltration analysis revealed that many immune cells were more abundant in the DGF group compared to the Immediate Graft Function (IGF) group. A two-gene prognostic signature was developed, which accurately predicted renal allografts prognosis.

Conclusions: The mitophagy-related gene signatures demonstrated high predictive accuracy for DGF and renal allograft loss. Our study may provide new perspectives on prognosis and treatment strategies post-kidney transplantation.

The discovery and use of cyclosporine since its inception into the clinics in the '70s and up have played a crucial role in the advancement of transplant therapy and containment of immune-based rejections. The drug had improved rates of acute rejections, and supported early graft survival. However, the long-term survival of renal allografts is still less prevalent, and an in-depth analysis and reported findings led us to believe that there is a chronic irreversible component to the drug that is tackled through its metabolites, and causes toxicity, which led to new therapies, including monoclonal antibody based medications. A recap of the immunosuppressive effects and entwined toxicity of the drug, now relegated to solid transplants, overviews the past protocols used to minimize and avoid, or use in combination with this calcineurin inhibitor class drug with other drugs. The current review circumvents the cyclosporine's mechanism of action, pathophysiology, cytochrome roles, and other factors associated with acute and chronic toxicity. It also attempts to find conclusive strategies reported in recent studies to avoid its toxic side effects and develop a safe-use strategy for the drug. Gastrointestinal decontamination, supporting the airway, monitoring for signs of respiratory insufficiency, monitoring for severe reactions such as seizures, administration of oxygen, and avoiding the administration of drugs that increase the blood levels of cyclosporine are beneficial interventions when encountering cyclosporine toxicity cases. The constrained therapeutic outcome has also led to redesign, and combine formulation to review the pharmacokinetics of the drug.

Background: High-resolution typing of human leukocyte antigen (HLA) may revolutionize the field of kidney transplantation by selection of low immunogenic grafts. The new 250-nautical mile circle allocation system offers a unique opportunity to find low HLA immunogenic donors for eligible recipients.

Methods: 501 transplant candidates from the University of Toledo Medical Center (UTMC) between 2015 and 2019, registered at the Scientific Registry of Transplant Recipients (SRTR) were virtually matched to 4812 donors procured within 250-nautical miles using an in-house-developed simulation algorithm. Immunogenicity of HMS (hydrophobic mismatch score) ≤10 was measured based on imputed high-resolution HLAs. Simulated "optimal" matches with a KDPI≤50 % were compared with the transplant cohort between 2000 and 2010 with their kidney allograft survivals.

Results: Out of 501 recipients 500 (99.8 %) were matched with donors ≤10 HMS and KDPI ≤50 %. The average HMS value for simulated transplants was 1.4 (range 0-10) versus 6.3 (range 0-75) in the retrospective cohort (p < 0.001). The simulated model had a median mismatch number of 3/6, while the reference cohort 4/6 among HLA-A/B/DR antigens (p < 0.001). The estimated median graft survival was 18.2 years for the simulated cohort vs. 13.4 years in the real-life cohort (p < 0.001), gaining 4.9 years per transplant and 2450 survival years for all patients. For year 2014, out of 98 patients and 659 donors, each recipient had a median number of 141 donors (HMS < 10; range 8-378). Similar values were found for patients between 2015 and 2019.

Conclusion: Donors within 250-nautical miles proffers excellent and multiple options for finding well-matched low immunogenic HLA kidney donors for UTMC patients, thus significantly improving their chances for long-term allograft survival.