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UNASSIGNED: Hematopoietic stem cell transplantation (HSCT) is an approach that has significantly improved the prognosis and survival of hematological patients. However, ovarian dysfunction and infertility following HSCT have gained increasing attention. Live births have been reported following ovarian tissue cryopreservation prior to HSCT and subsequent retransplantation of these tissues. Still, the feasibility of ovarian tissue cryopreservation (OTC) following graft failure (GF) of HSCT remains unknown. In this study, we report the first case of OTC following a GF of allogenic HSCT (allo-HSCT), as well as the cryopreservation of four MII oocytes via in vitro maturation with informed consent. Despite the lack of clinical outcomes after cryopreserved ovarian tissue retransplantation, we documented an interesting case in a woman after GF of allo-HSCT exhibiting functional ovaries and emphasized a clinical dilemma: whether OTC should be offered to women suffering from GF of HSCT.
UNASSIGNED: A 22-year-old woman with severe aplastic anemia who had suffered GF of allo-HSCT from her sibling brother [HLA allele match (7/10)] with a reduced dose conditioning regimen including fludarabine, cyclophosphamide, and antithymocyte globulin came to our reproductive center for fertility preservation, as she was about to receive the second allo-HSCT. We evaluated the ovarian reserve of this patient. Hormone assessments showed an anti-Müllerian hormone level of 3.921 ng/mL, a follicle-stimulating hormone level of 5.88 IU/L, a luteinizing hormone level of 10.79 IU/L, and an estradiol level of 33.34 pg/mL. Antral follicle counts accessed transvaginally showed 12-15 follicles. All assessments indicated a well-protected ovarian reserve. Due to the urgency of the second allo-HSCT, the patient decided to undergo ovarian cryopreservation. Laparoscopic surgery proceeded. Ovarian tissues were successfully cryopreserved using vitrification technology, and histologic evaluation demonstrated a follicle density of 20 per 2 × 2 mm2 biopsy with good viability. Four MII oocytes were obtained via in vitro maturation technology and cryopreserved. After the second HSCT, the patient relieved from aplastic anemia but suffered iatrogenic premature ovarian failure as predicted.
UNASSIGNED: OTC is applicable to fertility preservation in those undergoing GF of HSCT with benign hematological disorders and especially those who are about to receive the second HSCT.

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OBJECTIVE: This study aims to evaluate the presence of EBV, HCMV, and BKV genomic sequences in the plasma samples (active infection/viremia) of kidney transplant recipients suspected of rejection and to investigate host and risk factors related to the activation of these viruses in these patients.
METHODS: In this cross-sectional single-center study, plasma samples were collected from 98 suspected kidney transplant rejection patients at Labafinejad Hospital, Tehran, Iran, between December 2022 and June 2023. Quantitative real-time PCR assays for HCMV, EBV, and BK were performed using GeneProof Real-time PCR kits. ROC curve analysis was used to determine the viral load cutoff point for each virus.
RESULTS: HCMV active viremia was detected in 18 (18.36%) recipients, EBV active viremia in 7 (7.14%), and BKV active viremia in 5 (5.10%). ROC results indicated viral load cutoff points of 778, 661, and 457 points for HCMV, EBV, and BKV, respectively. The duration of time after transplantation significantly differed between active viremia and no viremia groups (120.5 vs. 46 months, P = 0.014). In the BKV active viremia group, the increase in creatinine compared to baseline creatinine was significantly higher than in the no viremia group (2.7 vs. 0.8, P = 0.017). The odds ratio of HCMV active viremia in patients taking tacrolimus was 2.84 times higher, and the odds of HCMV active viremia in patients taking antithymocyte globulin was 3.01 times higher than in patients not taking these drugs.
CONCLUSIONS: Rapid and timely diagnosis of viral active infections in kidney transplant patients is crucial for effective disease management and implementation of appropriate treatment strategies. Identifying potential risk factors, including host and treatment-related factors that influence transplantation, can facilitate the development of suitable preventive strategies.

HLA donor specific antibodies (DSA) are implicated in antibody-mediated rejection (AMR), graft dysfunction and failure in kidney transplant (KT) recipients. Non-HLA antibodies including angiotensin II type 1 receptor (AT1R) may also play a role in AMR, impact graft function and survival. Data is limited in paediatric KT cohorts. We aimed to assess the prevalence and effect of pre-transplant AT1R antibodies on rejection, graft function and survival in paediatric KT recipients. This was a retrospective cohort study conducted across two paediatric centres including KT recipients with a pre-transplant AT1R antibody level. Outcomes included rejection, de novo DSA formation, graft function, failure, proteinuria and hypertension. Of 71 individuals, 72% recorded a positive pre-transplant AT1R Ab level (≥17 U/mL). Over a median follow-up of 4.7 years, AT1R Ab positivity demonstrated a trend towards increased risk of rejection however was not statistically significant (HR 3.45, 95% CI 0.97-12.35, p-value 0.06). Sensitivity analysis with AT1R Ab levels of ≥25 U/mL (HR 2.05 95% CI 0.78-5.39, p-value 0.14) and ≥40 U/mL (HR 1.32, CI 95% 0.55-3.17, p-value 0.53) validated this. De novo DSA formation occurred more frequently with AT1R Ab positivity (41% vs. 20%, p-value 0.9). AT1R Ab was not associated with hypertension, proteinuria, graft failure or dysfunction. In conclusion, this cohort study demonstrated a high prevalence of pre-transplant AT1R Ab positivity (72%). AT1R Ab positivity demonstrated a trend towards increased risk of rejection and de novo DSA formation however did not meet statistical significance. There was no association between AT1R Ab and hypertension, proteinuria, graft failure or dysfunction.

BACKGROUND: Glycosylation is a complex and fundamental metabolic biosynthetic process orchestrated by multiple glycosyltransferases (GT) and glycosidases enzymes. Functions of GT have been extensively examined in multiple human diseases. Our study investigated the potential role of GT genes in T-cell mediated rejection (TCMR) and possible prediction of graft loss of kidney transplantation.
METHODS: We downloaded the microarray datasets and GT genes from the GEO and the HUGO Gene Nomenclature Committee (HGNC) databases, respectively. Differentially expressed GT genes (DE-GTGs) were obtained by differential expression and Venn analysis. A TCMR diagnostic model was developed based on the hub DE-GTGs using LASSO regression and XGboost machine learning algorithms. In addition, a predictive model for graft survival was constructed by univariate Cox and LASSO Cox regression analysis.
RESULTS: We have obtained 15 DE-GTGs. Both GO and KEGG analyses showed that the DE-GTGs were mainly involved in the glycoprotein biosynthetic process. The TCMR diagnostic model exhibited high diagnostic potential with generally highly correlated accuracies [aera under the curve (AUC) of 0.83]. The immune characteristics analysis revealed that higher levels of immune cell infiltration and immune responses were observed in the high-risk group than in the low-risk group. In particular, the Kaplan-Meier survival analysis revealed that renal grafts in the high-risk group have poor prognostic outcomes than the low-risk group. The predictive AUC values of 1-, 2- and 3-year graft survival were 0.76, 0.81, and 0.70, respectively.
CONCLUSIONS: Our results indicated that GT genes could be used for diagnosis of TCMR and prediction of graft loss in kidney transplantation. These results provide new perspectives and tools for diagnosing, treating and predicting kidney transplant-related diseases.

Rationale: Understanding the immune mechanisms associated with liver transplantation (LT), particularly the involvement of tissue-resident memory T cells (TRMs), represents a significant challenge. Methods: This study employs a multi-omics approach to analyse liver transplant samples from both human (n = 17) and mouse (n = 16), utilizing single-cell RNA sequencing, bulk RNA sequencing, and immunological techniques. Results: Our findings reveal a comprehensive T cell-centric landscape in LT across human and mouse species, involving 235,116 cells. Notably, we found a substantial increase in CD8+ TRMs within rejected grafts compared to stable ones. The elevated presence of CD8+ TRMs is characterised by a distinct expression profile, featuring upregulation of tissue-residency markers (CD69, CXCR6, CD49A and CD103+/-,), immune checkpoints (PD1, CTLA4, and TIGIT), cytotoxic markers (GZMB and IFNG) and proliferative markers (PCNA and TOP2A) during rejection. Furthermore, there is a high expression of transcription factors such as EOMES and RUNX3. Functional assays and analyses of cellular communication underscore the active role of CD8+ TRMs in interacting with other tissue-resident cells, particularly Kupffer cells, especially during rejection episodes. Conclusions: These insights into the distinctive activation and interaction patterns of CD8+ TRMs suggest their potential utility as biomarkers for graft rejection, paving the way for novel therapeutic strategies aimed at enhancing graft tolerance and improving overall transplant outcomes.

OBJECTIVE: The aim of the study was to determine outcomes after heart transplantation for cytomegalovirus (CMV) mismatched patients (D+/R-) who underwent a surveillance and preemptive therapy protocol, compared to nonmismatch patients.
METHODS: A review of patient records from January 2010 to December 2020 with follow-up to October 2023 was done. The protocol consisted weekly surveillance with CMV PCR starting 4 weeks after transplant continuing up until the patient seroconverts or up to 3 months posttransplant if the patient does not seroconvert. Valganciclovir was given for 2 weeks to those who seroconverted.
RESULTS: Two hundred and twenty-one patients were included, and 23% were mismatched patients. Overall survival was not different between CMV groups (p = NS). Causes of death and morbidities were also not significantly different (p = NS). Sixty-six percent of mismatch patients seroconverted, and there was also a significantly older donor age in the seroconverted patients compared to nonseroconverted patients (41 ± 11 vs. 29 ± 12 years, p < 0.005), indicating a higher risk donor profile. A multivariate Cox regression including donor age showed that there was no increase in mortality in the seroconverted mismatches compared to nonmismatch patients (p = NS).
CONCLUSIONS: There is no significant increased mortality or morbidity using a CMV surveillance and preemptive therapy protocol. The effect of donor age on seroconversion of mismatches requires further validation.

The progress of transplantation has been propelled forward by animal experiments. Animal models have not only provided opportunities to understand complex immune mechanisms in transplantation but also served as a platform to assess therapeutic interventions. While small animals have been instrumental in uncovering new therapeutic concepts related to immunosuppression and immune tolerance, the progression to human trials has largely been driven by studies in large animals. Recent research has begun to explore the potential of porcine organs to address the shortage of available organs. The consistent progress in transplant immunology research can be attributed to a thorough understanding of animal models. This review provides a comprehensive overview of the available animal models, detailing their modifications, strengths, and weaknesses, as well as their historical applications, to aid researchers in selecting the most suitable model for their specific research needs.

BACKGROUND: The scarcity of suitable donor organs has led to the inclusion of Expanded Criteria Donor (ECD) kidneys to augment the donor pool, despite potential concerns regarding post-transplant outcomes.
METHODS: This retrospective study analyzed the clinical outcomes of a cohort of 317 kidney transplant recipients from deceased donors at a single center between 2008 and 2018. Patients were categorized into ECD and Standard Criteria Donor (SCD) groups, with primary nonfunctioning grafts excluded. Comprehensive laboratory evaluations were conducted, including HLA typing and serum creatinine levels. Immunosuppressive regimens were standardized, and statistical analyses were performed using the SPSS program.
RESULTS: The sample consisted of 83 (26.18%) patients who received kidney transplants from ECDs and 234 (73.82%) from SCDs. The ECD group showed a longer cold ischemia time (p = 0.019) and a higher rate of delayed graft function (DGF) compared with the SCD group. No significant differences were observed in graft survival (p = 0.370) or patient survival (p = 0.993) between the ECD and SCD groups. However, differences in graft survival were noted between the groups when stratified by DGF status: ECD with DGF vs. ECD without DGF (p = 0.029), ECD with DGF vs. SCD with DGF (p = 0.188), ECD with DGF vs. SCD without DGF (p = 0.022), ECD without DGF vs. SCD with DGF (p = 0.014), ECD without DGF vs. SCD without DGF (p = 0.340), and SCD with DGF vs. SCD without DGF (p = 0.195). No differences in patient survival rates were observed among these groups for all pairwise comparisons (p > 0.05) when stratified by donor criteria and DGF status.
CONCLUSIONS: Graft and patient survival rates were comparable between ECD and SCD kidney transplant recipients.