{"title":"Utilization of kidneys from tuberculosis-infected donors in renal transplantation: A case report.","authors":"Lu Yifan, Liu Yiting, Zhou Jiangqiao, Qiu Tao","doi":"10.1016/j.trim.2024.102151","DOIUrl":"https://doi.org/10.1016/j.trim.2024.102151","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":" ","pages":"102151"},"PeriodicalIF":1.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688885","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":"Clinical characteristics and outcomes of invasive pulmonary aspergillosis in renal transplant recipients: A single-center experience.","authors":"Jilin Zou, Zeya Jin","doi":"10.1016/j.trim.2024.102150","DOIUrl":"https://doi.org/10.1016/j.trim.2024.102150","url":null,"abstract":"<p><strong>Objective: </strong>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).</p><p><strong>Methods: </strong>We retrospectively examined 22 patients who were diagnosed with IPA post-RT and treated at our institution between 2005 and 2024.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":" ","pages":"102150"},"PeriodicalIF":1.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688878","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":"Identification of mitophagy-related gene signatures for predicting delayed graft function and renal allograft loss post-kidney transplantation.","authors":"Kaifeng Mao, Fenwang Lin, Yige Pan, Zhenquan Lu, Bingfeng Luo, Yifei Zhu, Jiaqi Fang, Junsheng Ye","doi":"10.1016/j.trim.2024.102148","DOIUrl":"10.1016/j.trim.2024.102148","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":" ","pages":"102148"},"PeriodicalIF":1.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644625","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}
Razan Alqadi, Amal Alqumia, Ibrahim S Alhomoud, Ahmed Alhowail, Maha Aldubayan, Hamdoon A Mohammed, Husam Alhomoud, Riaz A Khan
{"title":"Cyclosporine's immunosuppressive effects, entwined toxicity, and clinical modulations of an organ transplant drug.","authors":"Razan Alqadi, Amal Alqumia, Ibrahim S Alhomoud, Ahmed Alhowail, Maha Aldubayan, Hamdoon A Mohammed, Husam Alhomoud, Riaz A Khan","doi":"10.1016/j.trim.2024.102147","DOIUrl":"https://doi.org/10.1016/j.trim.2024.102147","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":" ","pages":"102147"},"PeriodicalIF":1.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644319","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}
Fayeq Jeelani Syed, Dulat Bekbolsynov, Robert C Green, Devinder Kaur, Obi Ekwenna, Puneet Sindhwani, Michael Rees, Stanislaw Stepkowski
{"title":"Potential of new 250-nautical mile concentric circle allocation system for improving the donor/recipient HLA matching: Development of new matching algorithm.","authors":"Fayeq Jeelani Syed, Dulat Bekbolsynov, Robert C Green, Devinder Kaur, Obi Ekwenna, Puneet Sindhwani, Michael Rees, Stanislaw Stepkowski","doi":"10.1016/j.trim.2024.102146","DOIUrl":"10.1016/j.trim.2024.102146","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":" ","pages":"102146"},"PeriodicalIF":1.6,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628799","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":"Association of PIRCHE-II score with anti-donor T-cell response and risk of de novo donor-specific antibody production in kidney transplant recipients","authors":"Hiroaki Yamane, Kentaro Ide, Yuka Tanaka, Masahiro Ohira, Hiroyuki Tahara, Seiichi Shimizu, Hiroshi Sakai, Ryosuke Nakano, Hideki Ohdan","doi":"10.1016/j.trim.2024.102145","DOIUrl":"10.1016/j.trim.2024.102145","url":null,"abstract":"<div><h3>Background</h3><div><em>De novo</em> donor-specific antibodies (dnDSAs) affect long-term outcomes of kidney transplantation (KT). A higher Predicted Indirectly ReCognizable Human Leukocyte Antigen (HLA) Epitopes (PIRCHE-II) score correlates with various clinical outcomes, including dnDSA formation. However, a detailed analysis of the relationship between the PIRCHE-II score and anti-donor T-cell response is lacking. Therefore, this study investigated the relationship between PIRCHE-II scores associated with dnDSA formation and mixed lymphocyte reaction results of anti-donor T-cell response.</div></div><div><h3>Methods</h3><div>Data of 105 adult living-donor KT recipients were retrospectively assessed.</div></div><div><h3>Results</h3><div>Of the 105 patients, 13.3 % developed dnDSAs during the observation period. The PIRCHE-II score at the HLA-DQ locus (PIRCHE-DQ) was significantly higher in patients with dnDSA formation than in those without. The incidence of dnDSA formation was significantly higher in the PIRCHE-DQ ≥ 77 group than in the PIRCHE-DQ < 77 group. The proportion of patients with increased anti-donor T-cell response was significantly higher in the PIRCHE-DQ ≥ 77 group than in the PIRCHE-DQ < 77 group before KT and at 4 and 5 years after KT.</div></div><div><h3>Conclusions</h3><div>PIRCHE-DQ may predict dnDSA formation and anti-donor T-cell response. Reducing the immunosuppressive drug dose in cases of high PIRCHE-DQ might not be prudent.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 102145"},"PeriodicalIF":1.6,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584388","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}
Yu Wang , Tingting Lan , Shao-Hua Wu , Jiangong Ma , Xunfeng Zou
{"title":"A betaine-contained solution reduced cold ischemia damage through inhibiting vacuolar degeneration in livers","authors":"Yu Wang , Tingting Lan , Shao-Hua Wu , Jiangong Ma , Xunfeng Zou","doi":"10.1016/j.trim.2024.102144","DOIUrl":"10.1016/j.trim.2024.102144","url":null,"abstract":"<div><div>A new osmoprotectant-containing multiple saccharide (MS) solution was formulated for this study. The primary objectives were to compare the effects of the MS solution with those of the University of Wisconsin (UW) solution and hypertonic citrate adenine (HCA) solution on liver cold preservation, as well as to investigate the mechanisms underlying osmolarity-induced injury. Rat livers were cold-stored for 18 h at 4 °C using the different solutions and subsequently subjected to 2 h of normothermic machine perfusion (NMP) for functional assessment. The livers were categorized into four groups: HCA, UW, MS, and a control group. Liver function and histological changes were evaluated using biochemical markers such as lactate dehydrogenase (LDH), alongside histopathological analysis. Additionally, the expression of aquaporin 9 (AQP9) and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) in hepatocytes was examined. Liver damage was significantly reduced in the UW and MS groups (<em>p</em> < 0.05). Histopathological analysis revealed a decrease in hepatic apoptosis and injury scores in the MS group compared to the HCA group (p < 0.05). No significant differences in liver function changes were observed between the MS and UW groups. Furthermore, examination of liver tissue showed increased H<sub>2</sub>O<sub>2</sub> fluorescence intensity and decreased AQP9 protein levels in livers exhibiting vacuolar degeneration. In conclusion, the MS solution demonstrated superior effectiveness in preserving the liver during cold storage by inhibiting vacuolar degeneration caused by intracellular H<sub>2</sub>O<sub>2</sub> accumulation.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 102144"},"PeriodicalIF":1.6,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569303","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":"Kidney transplantation after ABO-incompatible hematopoietic stem cell transplantation: A case report and literature review","authors":"Kazuro Kikkawa, Masahiro Tamaki, Kouhei Maruno, Tatsuya Hazama, Toshifumi Takahashi, Yuya Yamada, Masakazu Nakashima, Noriyuki Ito","doi":"10.1016/j.trim.2024.102143","DOIUrl":"10.1016/j.trim.2024.102143","url":null,"abstract":"<div><div>Although some studies have reported kidney transplantation for end-stage kidney disease after hematopoietic stem cell transplantation, few have reported kidney transplantation after ABO-incompatible hematopoietic stem cell transplantation. In this report, we describe a case of kidney transplantation after major ABO-incompatible HSCT and reviewed previous reports of kidney transplantation after hematopoietic stem cell transplantation. A 21-year-old male patient received major ABO-incompatible hematopoietic stem cell transplantation from an unrelated donor for B-lymphoblastic lymphoma. He developed chronic kidney disease requiring kidney replacement therapy because of drug toxicity and underwent ABO-compatible living donor kidney transplantation from his mother with standard immunosuppression. He had no anti-donor blood type antibody before kidney transplantation. Ten months after kidney transplantation, he is in good clinical condition with good renal function. Eighty-four cases of kidney transplantation after hematopoietic stem cell transplantation have been reported in literature. Among them, 25 recipients were from the same donor as hematopoietic stem cell transplantation. Out of these 25 recipients, 15 did not undergo maintenance immunosuppressive therapy. The low rejection incidence (14 %) and high rate of infection (32 %) and malignancy (10 %) suggest that kidney transplant recipients after hematopoietic stem cell transplantation are over-immunosuppressed. There were only three reports of kidney transplantation after ABO-incompatible hematopoietic stem cell transplantation, including the present case. Kidney transplantation may be an effective renal replacement therapy for end-stage kidney disease after hematopoietic stem cell transplantation, even in ABO-incompatible hematopoietic stem cell transplantation cases.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 102143"},"PeriodicalIF":1.6,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569306","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}
Tiago Xavier Silva , Evaldo Nascimento , Marcelo Gonçalves de Oliveira , Raquel A. Fabreti-Oliveira
{"title":"Impact of renal allograft histopathological findings on transplant patient outcomes and graft survival: A retrospective single-center study","authors":"Tiago Xavier Silva , Evaldo Nascimento , Marcelo Gonçalves de Oliveira , Raquel A. Fabreti-Oliveira","doi":"10.1016/j.trim.2024.102142","DOIUrl":"10.1016/j.trim.2024.102142","url":null,"abstract":"<div><h3>Introduction</h3><div>This study aimed to evaluate the reasons for kidney transplant dysfunction by analyzing allograft biopsy findings. We also compared clinical outcomes and graft survival rates in patients with and without <em>de novo</em> donor-specific antibodies (DSA).</div></div><div><h3>Methods</h3><div>This retrospective observational cohort study included 79 patients who underwent kidney allograft biopsy. The patients were divided into two groups based on the presence of anti-human leukocyte antigens (HLA) DSA antibodies. Laboratory evaluations included HLA-DSA and serum creatinine levels. The immunosuppressive therapy protocols were as follows: patients with single-antigen bead-measured sensitization (panel reactive antibody >50 %) received induction therapy, and all patients received triple therapy with tacrolimus or cyclosporine, prednisone, and mycophenolate sodium.</div></div><div><h3>Results</h3><div>Acute antibody-mediated rejection (AMR) occurred in 20.2 % of patients, whereas acute T-cell-mediated rejection (TCMR) was observed in 14 %. Interstitial fibrosis and tubular atrophy were observed in 53.8 % and 69.2 % of patients with <em>de novo</em> DSA, respectively, compared with 15.2 % and 87.9 % in the non-DSA group. Calcineurin inhibitors induced nephrotoxicity in 11.4 %, relapse of the underlying disease in 13.9 %, and infection in 7.6 % of biopsies. Differences in serum creatinine levels were observed between the <em>de novo</em> DSA and non-DSA groups from the third (<em>p</em> = 0.039), fifth (<em>p</em> = 0.028), and seventh years of follow-up (<em>p</em> = 0.012). The graft survival rate was lower in patients with <em>de novo</em> DSA than in those without (<em>p</em> = 0.036).</div></div><div><h3>Conclusions</h3><div>TCMR and AMR were the most common findings. The occurrence of AMR significantly impacted renal function and graft survival, and patients with <em>de novo</em> anti-HLA antibodies had poorer outcomes.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 102142"},"PeriodicalIF":1.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547669","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}
Yisheng Ji , Congcong Chen , Pei Lu , Zijie Wang , Hao Chen , Li Sun , Shuang Fei , Xiaobing Ju , Ruoyun Tan , Min Gu
{"title":"Nuclear factor of activated T cell cytoplasmic 1 (NFATc1) insertion gene polymorphism as a possible trigger in acute T cell-mediated rejection (aTCMR) after kidney transplantation","authors":"Yisheng Ji , Congcong Chen , Pei Lu , Zijie Wang , Hao Chen , Li Sun , Shuang Fei , Xiaobing Ju , Ruoyun Tan , Min Gu","doi":"10.1016/j.trim.2024.102139","DOIUrl":"10.1016/j.trim.2024.102139","url":null,"abstract":"<div><h3>Background</h3><div>To investigate the potential regulatory role of gene insertion or deletion (in/del) polymorphism in the occurrence of acute T cell-mediated rejection (aTCMR) after kidney transplantation.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed the 5-year follow-up data of 133 recipients who underwent renal transplantation at the First Affiliated Hospital of Nanjing Medical University between February 1, 2010, and December 1, 2015. With target sequencing based on next-generation sequencing (NGS), tagger in/dels selection involved calculating the Hardy-Weinberg equilibrium (HWE), Minor Allele Frequency (MAF), and the linkage disequilibrium (LD) blocks. Significant in/dels associated with aTCMR were identified by intersecting the results obtained through analysis of covariance (ANCOVA) of clinical cofounders and model analysis in Rstudio using the “SNPassoc” package. Additionally, logistic models were employed to assess the associations between genotypes and the aTCMR occurrence in 5 years after surgery.</div></div><div><h3>Results</h3><div>NFATc1 rs55741427 insertion was identified to be significantly associated with the post-surgery aTCMR(OR = 2.66, <em>P</em> < 0.001). We constructed a conclusive model containing the occurrence of delayed graft function (DGF) and the insertion polymorphism of rs55741427, showing a favorable predictive ability (AUC = 0.766) for aTCMR after surgery. Based on the receiver operating characteristic (ROC) curve, all cases were stratified into aTCMR high-risk and low-risk groups. Kaplan-Meier curves for two groups revealed that the aTCMR high-risk group exhibited a more unfavorable graft survival outcome (<em>P</em> = 0.0048).</div></div><div><h3>Conclusion</h3><div>Insertion mutation of rs55741427 was found to be statistically correlated with the post-surgery aTCMR during 5 years of follow-up. Our model identified DGF and insertion of rs55741427 as two crucial aTCMR-related hazards, and aTCMR high-risk group showed a worse graft prognosis.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 102139"},"PeriodicalIF":1.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508759","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}