Transplant International最新文献

The scarcity of donors has prompted the growing utilization of steatotic livers, which are susceptible to injuries following orthotopic liver transplantation (OLT). This study aims to assess the efficacy of multidrug donor preconditioning (MDDP) in alleviating injuries of steatotic grafts following rat OLT. Lean rats were subjected to a Western-style diet with high-fat (HF) and high-fructose (HFr) for 30 days to induce steatosis. Both lean and steatotic livers were implanted into lean recipients fed with a chow diet after OLT. The HF + HFr diet effectively elevated blood triglyceride and cholesterol levels and induced fat accumulation in rat livers. Our results demonstrated a significant decrease in alanine aminotransferase levels (p = 0.003), aspartate aminotransferase levels (p = 0.021), and hepatic Suzuki scores (p = 0.045) in the steatotic rat liver allograft group following MDDP treatment on post-operation day (POD) 7. Furthermore, the survival rates of steatotic rat liver allografts with MDDP (19/21, 90.5%) were significantly higher than those in the steatotic control (12/21, 57.1%, *p = 0.019). These findings indicate that MDDP treatment improves steatotic rat liver allograft function and recipient survival following OLT.

The Council of Europe (CoE) and the European Union (EU) share the same fundamental values, i.e., human rights, democracy and the rule of law, but are separate entities which perform different, yet complementary, roles. The CoE brings together governments from across Europe, and beyond, to agree minimum legal standards in a wide range of areas. CoE monitors how countries apply the standards that they have chosen to sign up to. It provides technical assistance, often working together with the EU. The EU refers to those same European values as a key element of its political and economic integration processes. It often builds upon CoE standards when drawing up legal instruments and agreements which apply to the member states, furthermore, monitoring work in its dealings with neighbouring countries, many of which are CoE member states. At CoE, the European Committee on Organ Transplantation (CD-P-TO) is the steering committee in charge of organ transplantation activities. In the EU, the regulation on Substances of Human Origin (SoHO) was endorsed in 2024. The CoE and the EU thave concluded an agreement expanding their co-operation in the field of SoHO. In the BTC regulation, xenotransplantation is not included.

Intestinal microsporidiosis caused by Enterocytozoon bieneusi is an opportunistic infection that especially affects solid organ transplant (SOT) recipients. Management revolves around tapering the immunosuppressive regimen and/or using a specific anti-microsporidia treatment, but only fumagillin has demonstrated efficacy for treatment of this infection. Since fumagillin has been commercially discontinued, nitazoxanide is increasingly being used in this indication. We aimed to describe therapeutic management of E. bieneusi infections in this context. We conducted a French nationwide observational retrospective study on reported cases of E. bieneusi infections in SOT recipients. We identified 154 cases: 64 (41.6%) were managed by simply modifying the immunosuppressive regimen, 54 (35.1%) were given fumagillin, and 36 (23.4%) were given nitazoxanide. Clinical remission rate ranged from 77.8% to 90.7% and was not significantly different between therapeutic strategies but tended to be lower with nitazoxanide. Stool negativization rate was highest with fumagillin (91.7%) and lowest with nitazoxanide (28.6%). Relapses occurred in 6.9% of cases and were more frequent with nitazoxanide (14.3%). This study shows that tapering immunosuppression can result in a satisfactory remission rate but is sometimes accompanied by relapses. Nitazoxanide had limited effectiveness, whereas fumagillin had good results that provide a solid rationale for bringing fumagillin back to market.

Trial registration number: ClinicalTrials.gov ID: NCT05417815.

While the Banff classification dichotomizes kidney allograft rejection based on the localization of the cells in the different compartments of the cortical kidney tissue [schematically interstitium for T cell mediated rejection (TCMR) and glomerular and peritubular capillaries for antibody-mediated rejection (AMR)], there is a growing evidences that subtyping the immune cells can help refine prognosis prediction and treatment tailoring, based on a better understanding of the pathophysiology of kidney allograft rejection. In the last few years, multiplex IF techniques and automatic counting systems as well as transcriptomics studies (bulk, single-cell and spatial techniques) have provided invaluable clues to further decipher the complex puzzle of rejection. In this review, we aim to better describe the inflammatory infiltrates that occur during the course of kidney transplant rejection (active AMR, chronic active AMR and acute and chronic active TCMR). We also discuss minor components of the inflammatory response (mastocytes, eosinophils, neutrophils, follicular dendritic cells). We conclude by discussing whether the over simplistic dichotomy between AMR and TCMR, currently used in clinical routine, remains relevant given the great diversity of immune actors involved in rejections.

After kidney transplantation, conversion to belatacept is a promising alternative in patients with poor graft function or intolerance to calcineurin inhibitors. The risk of acute rejection has not been well described under these conditions. Here we present a retrospective multicenter study investigating the occurrence of acute rejection after conversion in 901 patients (2011-2021). The incidence of cellular and humoral rejection was 5.2% and 0.9%, respectively. T-cell mediated rejection (TCMR) occurred after a median of 2.6 months after conversion. Out of 47 patients with TCMR, death-censored graft survival was 70.1%, 55.1% and 50.8% at 1 year, 3 years and 5 years post-rejection, respectively. Eight patients died after rejection, mainly from infectious diseases. We compared these 47 patients with a cohort of kidney transplant recipients who were converted to belatacept between 2011 and 2017 and did not develop rejection (n = 238). In multivariate analysis, shorter time between KT and conversion, and the absence of anti-thymocyte globulin induction after KT were associated with the occurrence of TCMR after belatacept conversion. The occurrence of rejection after conversion to belatacept appeared to be less frequent than with de novo use. Nevertheless, the risk of graft loss could be significant in patients with already low renal function.

HLA typing and matching have been crucial in kidney transplantation, but methods for assessing tissue histocompatibility have advanced significantly. While serological-level HLA typing remains common, it captures only a small fraction of true HLA variation, and molecular matching is already replacing traditional HLA matching. Recent studies have expanded our understanding of genetic tissue compatibility beyond HLA loci. Candidate gene analyses and genome-wide association studies (GWAS) have identified genetic factors linked to post-transplant complications, though replication of these findings is challenging. An alternative approach involves genome-wide matching of genes or genetic variations. This method has shown promise in hematopoietic stem cell and kidney transplantation. For instance, homozygous gene deletions in LIMS1 or complement factor H (CFH) genes have been associated with acute rejection risk. This may be due to alloimmune responses against proteins absent in the patient but present in the graft, or due to the missing protein's function. Genetic studies in clinical medicine face challenges due to the interplay of genetic and environmental factors, necessitating large datasets for meaningful associations. International collaboration and large consortia, like iGeneTRAin, are essential for validating findings and advancing the field. This review highlights recent advancements in immunogenetics and tissue histocompatibility, emphasizing future research directions.

Xenotransplantation of porcine organs has made remarkable progress towards clinical application. A key factor has been the generation of genetically multi-modified source pigs for xenotransplants, protected against immune rejection and coagulation dysregulation. While efficient gene editing tools and multi-cistronic expression cassettes facilitate sophisticated and complex genetic modifications with multiple gene knockouts and protective transgenes, an increasing number of independently segregating genetic units complicates the breeding of the source pigs. Therefore, an optimal combination of essential genetic modifications may be preferable to extensive editing of the source pigs. Here, we discuss the prioritization of genetic modifications to achieve long-term survival and function of xenotransplants and summarise the genotypes that have been most successful for xenogeneic heart, kidney, and islet transplantation. Specific emphasis is given to the choice of the breed/genetic background of the source pigs. Moreover, multimodal deep phenotyping of porcine organs after xenotransplantation into human decedents will be discussed as a strategy for selecting essential genetic modifications of the source pigs. In addition to germ-line gene editing, some of these modifications may also be induced during organ preservation/perfusion, as demonstrated recently by the successful knockdown of swine leukocyte antigens in porcine lungs during ex vivo perfusion.

Kidney retransplantations are associated with an increased risk of rejection and reduced graft survival compared to first transplantations, notably due to HLA sensitization. The impact of repeated eplet mismatches on retransplantation outcome has not been investigated. We retrospectively assessed the risk of antibody-mediated rejection (ABMR) and graft loss associated with preformed DSA targeting Repeated Eplet MisMatches (DREMM) in sensitized patients undergoing kidney retransplantation. We included 45 retransplanted patients with preformed DSA against the second donor. We determined HLA incompatibilities at the eplet levels, and the eplet target of the DSA using HLAMatchmaker^®. Repeated mismatches were more frequent at the eplet (87%) than at the antigenic level (22%), but were not associated with the risk of ABMR. The eplet specificity of the DSA revealed that 60% of patients (n = 27) had DREMM. The presence of DREMM was associated with a higher frequency of ABMR (70% versus 28%, P = 0.005) and with a lower death-censored graft survival (log-rank test, P = 0.01). However, in multivariate Cox model, we could not show that DREMM were associated with the risk of ABMR. In conclusion, this study suggests that identifying DREMM may be an interesting clinical tool, however further larger studies are necessary to precise their exact predictive value.