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Kidney transplantation is the most efficient renal replacement therapy. Current diagnostics for monitoring graft health are either invasive or lack precision. Metabolomics is an emerging discipline focused on the analysis of the small molecules involved in metabolism. Given the kidneys\' central role in metabolic homeostasis and previous observations of altered metabolites correlating with restricted kidney graft function, metabolomics is highly promising for the discovery of novel biomarkers and the development of novel diagnostics. In this perspective, we summarize the known metabolic roles for the kidney, discuss biomarkers of graft health and immune status emerging from metabolomics research, and provide our perspective on how these and future findings can be integrated in clinical practice to enable precision diagnostics.
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Posttransplantation complications pose a major challenge to the long-term survival and quality of life of organ transplant recipients. These complications encompass immune-mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation. Here, we provide a comprehensive overview of the clinical features, risk factors, and molecular mechanisms of major posttransplantation complications. We systematically summarize the current understanding of the immunological basis of allograft rejection and graft-versus-host disease, the metabolic dysregulation associated with immunosuppressive agents, and the role of oncogenic viruses in posttransplantation malignancies. Furthermore, we discuss potential prevention and intervention strategies based on these mechanistic insights, highlighting the importance of optimizing immunosuppressive regimens, enhancing infection prophylaxis, and implementing targeted therapies. We also emphasize the need for future research to develop individualized complication control strategies under the guidance of precision medicine, ultimately improving the prognosis and quality of life of transplant recipients.

For patients with end stage heart disease and borderline hemodynamics, high HLA allosensitization presents a barrier for heart transplantation in a timely manner. Conventional desensitization protocols are inadequate in this context due to time constraints and for the most highly reactive immunologically. We previously reported performing heart after liver transplant with domino liver transplant (HALT-D) on a single patient without liver disease. We describe this patient\'s course to date as well as four subsequent patients listed for this novel therapy. This experience demonstrates that the liver effectively confers immunoprotection to the heart for patients with high-titer, preformed antibodies. This strategy may provide some measure of equity for demographic groups previously disadvantaged for heart transplantation due to allosensitization.

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The QuantiFERON CMV (QCMV) test evaluates specific adaptive immune system activity against CMV by measuring IFN-γ released by activated CD8+ T lymphocytes. We aimed to evaluate the QCMV test as a predictive tool for CMV manifestations and acute or chronic lung allograft rejection (AR and CLAD) in lung transplant (LTx) patients. A total of 73 patients were divided into four groups based on donor and recipient (D/R) serology for CMV and QCMV assay: group A low-risk for CMV infection and disease (D-/R-); group B and C at intermediate-risk (R+), group B with non-reactive QCMV and group C with reactive QCMV; group D at high-risk (D+/R-). Group D patients experienced higher viral replication; no differences were observed among R+ patients of groups B and C. D+/R- patients had a higher number of AR events and group C presented a lower incidence of AR. Prevalence of CLAD at 24 months was higher in group B with a higher risk of CLAD development (OR 6.33). The QCMV test allows us to identify R+ non-reactive QCMV population as the most exposed to onset of CLAD. This population had a higher, although non-significant, susceptibility to AR compared to the R+ population with reactive QCMV.

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. We prospectively assessed gene expression levels of 19 blood messenger RNAs, four antibodies targeting non-human leukocyte antigen (HLA) endothelial antigens, together with circulating anti-HLA donor-specific antibodies (DSA). The primary outcome was allograft rejection (antibody-mediated, T cell-mediated, or mixed) in the first year post-transplantation. Overall, 412 patients were included, with 812 biopsies paired with a blood sample. CD4 gene expression was significantly associated with rejection, while circulating anti-HLA DSA had a significant association with allograft rejection and a strong association with antibody-mediated rejection. All other tested biomarkers, including AKR1C3, CD3E, CD40, CD8A, CD9, CTLA4, ENTPD1, FOXP3, GZMB, ID3, IL7R, MS4A1, MZB1, POU2AF1, POU2F1, TCL1A, TLR4, and TRIB1, as well as antibodies against angiotensin II type 1 receptor, endothelin 1 type A receptor, C3a and C5a receptors, did not show significant associations with allograft rejection. The blood messenger RNAs and non-HLA antibodies did not show an additional value beyond standard of care monitoring parameters and circulating anti-HLA DSA to predict allograft rejection in the first year post-transplantation. Thus, our results open avenues for specifically designed studies to demonstrate the clinical relevance and implementation of other candidate non-invasive biomarkers in kidney transplantation practice.

BACKGROUND: Samples for transfusion rejected due to mislabelling can lead to harm when a patient has to be re-bled or has a transfusion or procedure delayed. Electronic labelling systems which scan the patient\'s identification band and generate a label at their side aim to reduce mislabelling and misidentification leading to wrong blood in tube (WBIT) errors. The 2022 National Comparative audit of sample collection aimed to compare national rates of sample mislabelling and WBIT to the 2012 audit and to examine the impact of electronic systems.
METHODS: All UK hospitals were invited to provide data on rejected transfusion samples and WBIT incidents in 1 month (October 2022) and were asked if they had electronic labelling.
RESULTS: Twenty-three thousand five hundred and eighty-four rejected samples were reported by 179 sites in 1 month. The rejection rate of 4.4% represents a 47% increase compared to 2012 (2.99%). There were 92 WBIT incidents, an incidence of 1 in 5882 samples-a 45% increase compared to 1 in 8547 in 2012. Twenty-three percent of sites can print a sample label at the patient\'s side, up by 224%. The six sites using only electronic sample labelling had a 46.9% lower rejection rate than sites using only hand-labelling but still reported WBIT.
CONCLUSIONS: The increase in sample rejection and WBIT may reflect pressures facing clinical staff, zero tolerance policies and the two-sample rule. A human factors approach to understanding and tackling underlying reasons locally is recommended. Electronic systems are associated with fewer labelling errors, but careful implementation and training is needed to maximise their safety benefits.

[This corrects the article DOI: 10.3389/fimmu.2024.1420351.].

Last twenties, tissue engineering has rapidly advanced to address the shortage of organ donors. Decellularization techniques have been developed to mitigate immune rejection and alloresponse in transplantation. However, a clear definition of effective decellularization remains elusive. This study compares various decellularization protocols using the human fascia lata model. Morphological, structural and cytotoxicity/viability analyses indicated that all the five tested protocols were equivalent and met Crapo\'s criteria for successful decellularization. Interestingly, only the in vivo immunization test on rats revealed differences. Only one protocol exhibited Human Leucocyte Antigen (HLA) content below 1% residual threshold, the only criterion preventing rat immunization with an absence of rat anti-human IgG switch after one month (N=4 donors for each of the 7 groups, added by negative and positive controls, n=28). By respecting a refined set of criteria, i.e. lack of visible nuclear material, <50ng DNA/mg dry weight of extracellular matrix, and <1% residual HLA content, the potential for adverse host reactions can be drastically reduced. In conclusion, this study emphasizes the importance of considering not only nuclear components but also major histocompatibility complex in decellularization protocols and proposes new guidelines to promote safer clinical development and use of bioengineered scaffolds.