Transplant immunology最新文献

{"title":"Transcriptomics-based exploration of shared M1-type macrophage-related biomarker in acute kidney injury after kidney transplantation and acute rejection after kidney transplantation","authors":"Jun Pei ,&nbsp;Jie Zhang ,&nbsp;Chengjun Yu ,&nbsp;Jin Luo ,&nbsp;Sheng Wen ,&nbsp;Yi Hua ,&nbsp;Guanghui Wei","doi":"10.1016/j.trim.2024.102066","DOIUrl":"10.1016/j.trim.2024.102066","url":null,"abstract":"<div><h3>Background</h3><p>Macrophage type 1 (M1) cells are associated with both acute kidney injury (AKI) during kidney transplantation and acute rejection (AR) after kidney transplantation. Our study explored M1-related biomarkers involved in both AKI and AR and their potential biological functions.</p></div><div><h3>Methods</h3><p>Based on the Gene Expression Omnibus (GEO) database, the immune cell infiltration levels and differentially expressed genes were examined in AKI and AR in the kidney transplantation; M1-related genes shared in AKI and AR were identified using weighted gene co-expression analysis (WGCNA) system. Subsequently, protein-protein interaction (PPI) networks and machine learning methods to identify Hub genes and construct diagnostic models. Both AKI model and AR rat models were built to validate the expressions of Hub genes and test the injury phenotype, oxidative stress markers, and inflammatory factors. Finally, the transcription factor (TF)-Hub gene and micro-RNA (miRNA)-Hub gene regulatory networks were constructed based on identified Hub genes.</p></div><div><h3>Results</h3><p>Out of 2167 differential expression genes (DEGs) in AKI and 2100 DEGs in AR, four M1-related Hub genes were obtained by PPI networks and machine learning methods, namely GBP2, TYROBP, CCR5, and TLR8. The calibration curves in the nomogram diagnostic model for these four Hub genes suggested the same predictive probability as an ideal model for AKI and AR after kidney transplantation (AUC values of the area under the ROC curve were all &gt;0.7). The same observations were confirmed in ischemia reperfusion injury (IRI) and AR rat models by identifying common four Hub genes (GBP2, TYROBP, TLR8, and CCR5). Western blots showed that these four Hub genes were significantly different in rat models of IRI and AR (all p&lt;0.05). Compared with the control group, IRI and AR groups showed aggravated histopathological damage and increased secretion of oxidative stress markers and inflammatory factors in rat kidneys (all p&lt;0.05). Finally, TF-Hub and miRNA-Hub gene regulatory networks were constructed to provide a theoretical basis for the regulation of Hub genes.</p></div><div><h3>Conclusion</h3><p>We identified four macrophage M1-related Hub genes shared among AKI and AR after kidney transplantation. These genes may be considered for diagnosis of AKI and AR after kidney transplantation.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"85 ","pages":"Article 102066"},"PeriodicalIF":1.5,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Belatacept based immunosuppression: What and when to combine?","authors":"Juliana Schilsky ,&nbsp;Reut Hod Dvorai ,&nbsp;Christine Yang ,&nbsp;Liye Suo ,&nbsp;Giovanna Saracino ,&nbsp;Rauf Shahbazov","doi":"10.1016/j.trim.2024.102050","DOIUrl":"10.1016/j.trim.2024.102050","url":null,"abstract":"<div><h3>Introduction</h3><p>This study examines the effect of belatacept based salvage regimens on kidney transplant outcomes.</p></div><div><h3>Methods</h3><p>This single-center retrospective study included all adult kidney transplant recipients between 2011 and 2022 who were converted to belatacept salvage therapy during their follow up. eGFR, graft survival, incidence of infections and neoplasia, histology and DSA data were collected through systematic review of the medical record.</p></div><div><h3>Results</h3><p>Patients were divided into 3 groups based on salvage regimen: Mycophenolate mofetil/belatacept (MMF/Bela) (<em>n</em> = 28), low-dose Calcineurin inhibitors/belatacept (CNI/Bela) (<em>n</em> = 22), and low-dose Calcineurin inhibitors/ Mycophenolate mofetil /belatacept (CNI/MMF/Bela) (<em>n</em> = 13). Patients with antibody-mediated rejection were more likely to receive CNIs in addition to belatacept (low-dose CNI/MMF/Bela 54%, low-dose CNI/Bela 45%, MMF/Bela 3.6%, <em>p</em> &lt; 0.001). DSA decreased in all groups after transition to belatacept by 15.67% (<em>p</em> = 0.15). No difference in Glomerular filtration rate (eGFR) over time was observed between the groups, and eGFR remained stable over the first year after transition to belatacept. The incidence of death and allograft failure was similar between the groups (low- dose CNI/MMF/Bela <em>n</em> = 3, low-dose CNI/Bela <em>n</em> = 7, MMF/Bela <em>n</em> = 4; <em>p</em> = 0.41). Patients in the low-dose CNI/Bela cohort who were transitioned to belatacept within 6 months from transplant showed a decline in eGFR over the first year after transition, while the other treatment cohorts demonstrated stable or slight increase in eGFR.</p></div><div><h3>Conclusions</h3><p>The present study demonstrates comparable transplant outcomes in terms of eGFR, graft survival, incidence of infections and neoplasia, rejection rate and donor specific antibody (DSA) in three belatacept-based maintenance immunosuppression regimens supporting the safety and efficacy of these therapeutic options.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"85 ","pages":"Article 102050"},"PeriodicalIF":1.5,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful bilateral lung transplantation in a five-year-old child with pulmonary interstitial fibrosis caused by an ABCA3 gene mutation","authors":"Feifan Ge ,&nbsp;Jialong Liang ,&nbsp;Jintao Zhou ,&nbsp;Yuan Chen,&nbsp;Jingyu Chen,&nbsp;Shugao Ye","doi":"10.1016/j.trim.2024.102056","DOIUrl":"10.1016/j.trim.2024.102056","url":null,"abstract":"<div><p>The ATP-binding cassette subfamily A member 3 (ABCA3) protein plays a fundamental role in surfactant homeostasis. Most children with ABCA3 gene mutations develop pulmonary interstitial fibrosis leading to the development of interstitial lung disease. Since traditional medicine does not offer effective therapy, the best option is lung transplantations, especially bilateral lung transplantations. We are reporting the case of a successful bilateral lung transplantation in a five-year-old child with pulmonary interstitial fibrosis caused by ABCA3 gene mutations. This successful transplantation enabled the patient to get rid of chronic cough and tachypnea.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"85 ","pages":"Article 102056"},"PeriodicalIF":1.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141133109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting kidney allograft survival with explainable machine learning","authors":"Raquel A. Fabreti-Oliveira ,&nbsp;Evaldo Nascimento ,&nbsp;Luiz Henrique de Melo Santos ,&nbsp;Marina Ribeiro de Oliveira Santos ,&nbsp;Adriano Alonso Veloso","doi":"10.1016/j.trim.2024.102057","DOIUrl":"10.1016/j.trim.2024.102057","url":null,"abstract":"<div><h3>Introduction</h3><p>Despite significant progress over the last decades in the survival of kidney allografts, several risk factors remain contributing to worsening kidney function or even loss of transplants. We aimed to evaluate a new machine learning method to identify these variables which may predict the early graft loss in kidney transplant patients and to assess their usefulness for improving clinical decisions.</p></div><div><h3>Material and methods</h3><p>A retrospective cohort study was carried out with 627 kidney transplant patients followed at least three months. All these data were pre-processed, and their selected features were used to develop an automatically working a machine learning algorithm; this algorithm was then applied for training and parameterization of the model; and finally, the tested model was then used for the analysis of patients' features that were the most impactful for the prediction of clinical outcomes. Our models were evaluated using the Area Under the Curve (AUC), and the SHapley Additive exPlanations (SHAP) algorithm was used to interpret its predictions.</p></div><div><h3>Results</h3><p>The final selected model achieved a precision of 0.81, a sensitivity of 0.61, a specificity of 0.89, and an AUC value of 0.84. In our model, serum creatinine levels of kidney transplant patients, evaluated at the hospital discharge, proved to be the most important factor in the decision-making for the allograft loss. Patients with a weight equivalent to a BMI closer to the normal range prior to a kidney transplant are less likely to experience graft loss compared to patients with a BMI below the normal range. The age of patients at transplantation and Polyomavirus (BKPyV) infection had significant impact on clinical outcomes in our model.</p></div><div><h3>Conclusions</h3><p>Our algorithm suggests that the main characteristics that impacted early allograft loss were serum creatinine levels at the hospital discharge, as well as the pre-transplant values such as body weight, age of patients, and their BKPyV infection. We propose that machine learning tools can be developed to effectively assist medical decision-making in kidney transplantation.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"85 ","pages":"Article 102057"},"PeriodicalIF":1.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141136390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of donor-specific antibody with low mean fluorescence intensity on allograft outcomes in kidney transplant","authors":"Rungthiwa Kitpermkiat ,&nbsp;Surasak Kantachuvesiri ,&nbsp;Sansanee Thotsiri ,&nbsp;Duangtawan Thammanichanond ,&nbsp;Lionel Rostaing ,&nbsp;Punlop Wiwattanathum","doi":"10.1016/j.trim.2024.102054","DOIUrl":"10.1016/j.trim.2024.102054","url":null,"abstract":"<div><h3>Background</h3><p>Immune-mediated rejection is the most common cause of allograft failure in kidney transplant (KT) patients. Exposure to alloantigen, including human leukocyte antigen (HLA), results in the production of donor-specific antibodies (DSA). There are limited data about low levels of mean fluorescence intensity (MFI) DSA, especially post-transplantation. This study evaluated allograft outcomes in KT patients with low MFI DSA.</p></div><div><h3>Methods</h3><p>From January 2007 to December 2021, KT patients who were tested for post-transplant DSA at Ramathibodi Hospital, Bangkok, Thailand, with the DSA MFI ≤ 1000 were evaluated. These KT patients were categorized into two groups: very low DSA (VLL; MFI = 1–500) and low DSA (LL; MFI = 501–1000). All KT patients were evaluated for the primary outcomes, such as the incidence of acute rejection, serum creatinine levels at one and five years after transplantation as well as allograft and patient survivals.</p></div><div><h3>Results</h3><p>Among 36 KT patients 25 were included as those with VLL and 11 as those with LL. The LL group had significantly higher T-cell mediated allograft rejection (TCMR) than the VLL group (45% vs. 12%, <em>P</em> = 0.04). In addition, 10 patients, 5 in the VLL group and 5 in the LL group developed antibody-mediated allograft rejection (ABMR). Both TCMR and ABMR were confirmed by biopsy results. There was a trend toward higher MFI in KT patients with ABMR than without ABMR (<em>P</em> = 0.22). At 5 post-transplant years, serum creatinine, allograft and patient survivals were comparable between these two groups. Furthermore, the univariate and multivariate analyzes revealed that the LL group was a high risk for rejection.</p></div><div><h3>Conclusion</h3><p>Low MFI DSA values after transplantation may be associated with a higher incidence of rejection, but this finding did not show differences in allograft and patient survival in this study's analysis.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102054"},"PeriodicalIF":1.5,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0966327424000704/pdfft?md5=543c38d942e511d6f6fee8bbbb437f4a&pid=1-s2.0-S0966327424000704-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal study on the trajectory and influencing factors of cognitive dysfunction in lung transplantation patients","authors":"Lei Cao ,&nbsp;Shugao Ye ,&nbsp;Yuan Chen ,&nbsp;You Pei ,&nbsp;Jingyu Chen ,&nbsp;Xianwen Li","doi":"10.1016/j.trim.2024.102053","DOIUrl":"10.1016/j.trim.2024.102053","url":null,"abstract":"<div><h3>Introduction</h3><p>Lung transplantation is an effective method for treating end-stage lung disease. It prolongs the survival time of patients, improves the quality of life, and prevents the degree of mental disability. In particular, postoperative cognitive dysfunction (POCD) is one of the complications after lung transplantation. Despite this, longitudinal studies on the identification and heterogeneity of cognitive dysfunction subgroup trajectories in transplant patients are lacking. Therefore<strong>,</strong> our study aimed to evaluate the factors that influence POCD in lung transplant patients.</p></div><div><h3>Methods</h3><p>This prospective longitudinal study included patients who underwent lung transplantation at the transplant center of Wuxi People's Hospital from September 2022 to September 2023. Patients with lung transplants were evaluated at 8 days (T1), 1 month (T2), 3 months (T3), and 6 months (T4) after the operation. The general information questionnaire evaluated cognitive functions using the Montreal Cognitive Assessment (MoCA) numerical rating scale (NRS) and the digital pain assessment to obtain the POCD values. Latent category growth model (LCGM) analysis was used to identify heterogeneous POCD subgroups in the four observation periods. Univariate and logistic regression analyses were used to identify factors affecting POCD classification and independent risk factors.</p></div><div><h3>Results</h3><p>Based on clinical outcomes, 79 patients completed all four surveys, of whom 16 were lost during the follow-up period (loss rate, 16.8%). The cognitive function by MoCA NRS score was 14.18 ± 5.32 points on day 8 (T1), 22.51 ± 5.13 points at 1 month (T2), 25.44 ± 3.61 at 3 months (T3), and 27.04 ± 3.03 points at 6 months (T4) after lung transplantation, showing an increasing trend. The LCGM, used to fit the trajectory of MoCA scores, observed a heterogeneous trajectory of changes in lung transplant patients. Based on this analysis, patients could be divided into two categories: those with high risk (25,32%) and those with low risk (54,68%). The single-factor analysis identified that POCD values were affected by early postoperative rehabilitation exercise, degree of pain, intensive care unit (ICU) stay time, and donor lung cold ischemia time (all <em>P</em> &lt; 0.05). Using the low-risk group as the reference class, logistic regression analysis showed that the model could correctly classify the subjects.</p></div><div><h3>Conclusion</h3><p>Our 6-month observation of lung transplant patients showed that the degree of cognitive dysfunction had an overall downward trend and that patients could be divided into two trajectories of high and low risk for POCD. Early postoperative rehabilitation exercise, degree of pain, ICU stay time, and donor lung cold ischemia time were all influencing factors for POCD in lung transplant patients.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102053"},"PeriodicalIF":1.5,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0966327424000698/pdfft?md5=39bad18d7db0f9b2797c03ea6ec1ab7d&pid=1-s2.0-S0966327424000698-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of subclinical ocular inflammation in the aqueous humor of patients with myopia following bilateral sequential collamer lens implantation","authors":"Xiao-Qin Wang ,&nbsp;Shi-Jie Zheng ,&nbsp;Yong-Guo Xiang ,&nbsp;Fan-Fan Huang ,&nbsp;Rong-Xi Huang ,&nbsp;Wen-Juan Wan ,&nbsp;Ke Hu","doi":"10.1016/j.trim.2024.102052","DOIUrl":"10.1016/j.trim.2024.102052","url":null,"abstract":"<div><h3>Background</h3><p>The aqueous humor, a transparent fluid secreted by the ciliary body, supports the lens of the eyeball. In this study, we analyzed the cytokine and chemokine profiles within the aqueous humor of the contralateral eye post-implantation of an implantable collamer lens (ICL) to evaluate potential subclinical inflammation in the second eye subsequent to ICL implantation in the first eye.</p></div><div><h3>Methods</h3><p>Aqueous humor samples were procured from both eyes of 40 patients (totaling 80 eyes) prior to bilateral ICL insertion. Subsequently, a comprehensive statistical analysis was conducted using the Luminex assay to quantify 30 different cytokines in these samples.</p></div><div><h3>Results</h3><p>Compared to the first eye, the aqueous humor of the second eye demonstrated decreased concentrations of IFN-γ (<em>P</em> = 0.038), IL-13 (<em>P</em> = 0.027), IL-17/IL-17 A (<em>P</em> = 0.012), and IL-4 (<em>P</em> = 0.025). No significant differences were observed in other cytokine levels between the two groups. Patients were then categorized based on the postoperative rise in intraocular pressure (IOP) in the first eye. The group with elevated IOP displayed elevated levels of EGF in the aqueous humor of the first eye (<em>P</em> = 0.013) and higher levels of PDGF-AB/BB in the aqueous humor of the second eye (<em>P</em> = 0.032) compared to the group with normal IOP. Within the elevated IOP group, the levels of EGF (<em>P</em> = 0.013) and IL-17/IL-17 A (<em>P</em> = 0.016) in the aqueous humor were lower in the second eye than in the first eye. In the normal IOP group, cytokine levels did not differ notably between eyes.</p></div><div><h3>Conclusion</h3><p>Following sequential ICL implantation, it appears that a protective response may be activated to mitigate subclinical inflammation in the second eye induced by the initial implantation in the first eye. Additionally, the increase in IOP subsequent to surgery in the first eye may correlate with the presence of inflammatory mediators in the aqueous humor.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"85 ","pages":"Article 102052"},"PeriodicalIF":1.5,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuances in the interpretation and utility of donor-derived cell-free DNA in lung transplantation following allogeneic hematopoietic stem cell transplantation – Case report","authors":"Suresh Manickavel ,&nbsp;Renata Glehn-Ponsirenas ,&nbsp;Jennifer Gray ,&nbsp;Yuka Furuya ,&nbsp;Dennis Fu ,&nbsp;Natali Gulbahce ,&nbsp;Robert Woodward ,&nbsp;Hugo Kaneku ,&nbsp;Juan Castillo-Fernandez ,&nbsp;Juan Salgado ,&nbsp;Andres Pelaez ,&nbsp;Mauricio Pipkin ,&nbsp;Tiago Machuca ,&nbsp;Neeraj Sinha","doi":"10.1016/j.trim.2024.102055","DOIUrl":"10.1016/j.trim.2024.102055","url":null,"abstract":"<div><p>Respiratory complications following allogeneic HSCT can lead to severe morbidity and mortality. Lung transplantation (LT) is a potential treatment for select patients with late-onset non-infectious pulmonary complications post-HSCT. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive biomarker for monitoring the health of allografts following LT. However, its utility in a multi-genome setting of LT after HSCT has not yet been clinically validated. Here we describe a case of a 75-year-old, male patient who underwent single-lung transplantation for BOS related to chronic GVHD and presented with persistently elevated dd-cfDNA levels. In a surveillance biopsy, the patient was diagnosed with mild acute cellular rejection at three months. The patient's lung function remained stable, and the reported dd-cfDNA levels decreased after the rejection episode but remained elevated above levels that would be considered quiescent for LT alone. In this unique setting, as 3 different genomes contributed to the dd-cfDNA% reported value, valuable insight was obtained by performing further analysis to separate the specific SNPs to identify the contribution of recipient, lung-donor, and HSCT-donor cfDNA. This study highlights the potential utility of dd-cfDNA in the multi-genome setting of lung transplant post-HSCT, nuances that need to be considered while interpreting the results, and its value in monitoring lung rejection.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102055"},"PeriodicalIF":1.5,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beneficial effects of human umbilical cord mesenchymal stem cell (HUCMSC) transplantation on cyclophosphamide (CTX)-induced premature ovarian failure (POF) in Tibetan miniature pigs","authors":"Junhong Cai ,&nbsp;Xiaochen Liang ,&nbsp;Yuting Sun ,&nbsp;Shan Bao","doi":"10.1016/j.trim.2024.102051","DOIUrl":"10.1016/j.trim.2024.102051","url":null,"abstract":"<div><h3>Background</h3><p>Premature ovarian failure (POF), also known as primary ovarian insufficiency, is a common endocrine disease in young women. The emergence of regenerative medicine using stem cells may improve ovarian function and structure, and represents a promising prospect for POF treatment. In his study, we explored the therapeutic effects of human umbilical cord mesenchymal stem cell (HUCMSC) transplantation in a Tibetan miniature pig model of cyclophosphamide (CTX)-induced POF.</p></div><div><h3>Methods</h3><p>We cultured and identified HUCMSCs, labeled them with DiR iodide red dye, and implanted them into a CTX-induced model of POF in Tibetan miniature pigs. The daily weight changes were recorded, and the levels of estradiol (E2) and follicle-stimulating hormone (FSH) were measured on days 0, 7, and 14. At the end of the 21-day observation period, in vivo imaging of the bilateral ovaries was performed, and the ovarian index was measured. Ovarian tissue morphology and follicles were examined by hematoxylin-eosin staining. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay was employed to assess cell apoptosis, and immunohistochemistry was used to determine the levels of p-AKT, p-ERK1/2, BAX, and BCL2 expression.</p></div><div><h3>Results</h3><p>Our analysis indicated successful delivery of HUCMSCs to the ovaries of the POF pig model. Significant increases were observed in body weight, E2 levels, ovarian index, and number of normal follicles (all <em>p</em> &lt; 0.05). Moreover, FSH levels reduced and ovarian tissue morphology improved following HUCMSCs transplantation (all <em>p</em> &lt; 0.05). Importantly, upregulated p-AKT, p-ERK1/2, and BCL2 expression were observed, whereas the expression of BAX was suppressed (all <em>p</em> &lt; 0.05), suggesting the inhibition of ovarian cell apoptosis.</p></div><div><h3>Conclusion</h3><p>Our study highlights the significant therapeutic effects of HUCMSC transplantation on CTX-induced POF in a Tibetan miniature pig model.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102051"},"PeriodicalIF":1.5,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated human leukocyte antigens eplets, importance of typing the partner","authors":"Carolina dos Reis Ferreira ,&nbsp;Vítor Martinho da Silva Fernandes ,&nbsp;Sandra Cristina Ribeiro Tafulo ,&nbsp;Ana Cerqueira ,&nbsp;Ana Cristina Braga Rocha ,&nbsp;Ana Teresa Pires Morais Nunes ,&nbsp;Inês Passos Castro Neto Ferreira ,&nbsp;Maria Joana Cunha Santos ,&nbsp;Ana Teresa Marques Teixeira Pinho ,&nbsp;Isabel Cristina Tavares ,&nbsp;Maria Manuela Brito Bustorff Guerra ,&nbsp;Susana Maria Moreira Sampaio Norton","doi":"10.1016/j.trim.2024.102049","DOIUrl":"10.1016/j.trim.2024.102049","url":null,"abstract":"<div><h3>Introduction</h3><p>Antibody-mediated rejection (AMR) is the most common cause of immune-mediated allograft failure after kidney transplant and impacts allograft survival. Previous sensitization is a major risk factor for development of donor specific antibodies (DSA). AMR can have a wide range of clinical features such as impaired kidney function, proteinuria/hypertension or can be subclinical. HLA molecules have specific regions of antigens binding antibodies called epitopes and eplets are considered essential components responsible for immune recognition. We present a patient with subclinical AMR 1 week post transplantation.</p></div><div><h3>Case report</h3><p>A 48-year-old, caucasian woman with end-stage kidney disease (ESKD) secondary to autosomal dominant polycystic kidney disease (ADPKD) on peritoneal dialysis was registered in deceased donor waitlist. She was a hypersensitized patient from 3 prior pregnancies with a calculated panel reactive antibody of 93,48%. She was transplanted through kidney paired exchange donation with no evidence of DSA pre transplantation. Surgery and post-op were unremarkable with excellent and immediate graft function. Per protocol DSA levels on the 5th day was DR1 of 3300 MFI, with an increase in MFI by day 13 with 7820 MFI and a new B41 1979MFI. Allograft kidney biopsy findings were diagnostic of AMR and she was treated with immunoglobulin and plasmapheresis. As early onset AMR post transplantation was observed an anamnestic response was hypothesized from a previous exposure to allo-HLA. We decided to type her husband, her son's father, which was presented with DSA. Mismatch eplet analysis revealed a shared 41 T and 67LQ eplets between the donor and husband, responsible for the reactivity and new HLA class I B41 and HLA class II DR1 DSA, respectively.</p></div><div><h3>Discussion</h3><p>Shared eplets between the patient husband and donor was responsible for the alloimmune response and early development of DSAs. This case highlights the importance of early monitoring DSA levels in highly sensitized patients after transplant in order to promptly address and lower inflammatory damage. Mismatch eplet analysis can provide a thorough and precise evaluation of immune compatibility providing a useful technique to immune risk stratification, donor selection and post-transplant immunosuppressive therapy and monitoring.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102049"},"PeriodicalIF":1.5,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140903952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}