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Prevalence of anti-HLA antibodies among live related renal transplant recipients: A retrospective observational study from a tertiary healthcare Center in India. 抗hla抗体在活体相关肾移植受者中的流行:一项来自印度三级医疗保健中心的回顾性观察研究。
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-12-21 DOI: 10.1016/j.trim.2024.102164
Prashant Pandey, Amit Pande, Arghyadeep Marik, Amit Kumar Devra, Vijay Kumar Sinha, Anil Prasad Bhatt, Divya Setya, Smriti Mishra, Shantanu Jha

Aim: Detection of anti-HLA antibodies is crucial for pre-transplant histocompatibility testing, donor selection, and graft survival. The aim of this study was to evaluate the spectrum of anti-HLA antibodies among live related renal transplant recipients from one of the largest transplant centers in north India.

Methods: In this study, retrospective data of transplant workup done in past four years were analyzed using GraphPad Prism 9 Version 9.2.0 (La Jolla, CA, USA). All samples received for pre-transplant work-up if showed positive screening results underwent Luminex single antigen bead (L-SAB) assay. Antibodies identified on L-SAB were evaluated for their specificity and the strength of their mean florescence intensity (MFI).

Results: A total of 1250 renal transplant samples were included for analysis. Out of these, 458 (36.64 %) samples were found positive in screening tests algorithm. All 458 samples were further analyzed for both class I and class II HLA antibodies by Luminex single antigen bead (L-SAB) assay. In this study, we observed that anti-A*24:01, anti-B*15:01 and anti-C*07*01 were the three most prevalent anti-HLA antibodies identified against HLA-class I antigens. However, anti-DRB1*11:01, anti-DQA1*05:01-DQB1*03:01 and anti-DPA1*02:01-DPB1*17:01 were the most common anti-HLA antibodies identified against HLA-class II antigen. Furthermore, our study found a significant association between anti-HLA class I antibody and the history of pregnancy. However, in re-transplant cases, we observed the presence of antibodies both against HLA class I and II antigens.

Conclusion: For a transplant center, it is of utmost importance to have comprehensive knowledge about the prevalence of HLA antibodies, their MFI, and their association with various sensitization events. This study may immensely help transplant communities in selecting appropriate prospective organ donors, planning desensitization regimes, managing recipients' care and predicting transplant outcomes in live related renal transplantation.

目的:hla抗体的检测对移植前组织相容性检测、供体选择和移植物存活至关重要。本研究的目的是评估来自印度北部最大的移植中心之一的活体相关肾移植受者的抗hla抗体谱。方法:本研究采用GraphPad Prism 9 Version 9.2.0 (La Jolla, CA, USA)软件对近四年移植检查的回顾性资料进行分析。所有接受移植前检查的样本,如果筛选结果呈阳性,则进行Luminex单抗原珠(L-SAB)测定。在L-SAB上鉴定的抗体被评估其特异性和平均荧光强度(MFI)的强度。结果:共纳入1250例肾移植标本进行分析。其中458份(36.64 %)样本在筛选试验算法中发现阳性。采用Luminex单抗原珠(L-SAB)法对458份样品进行I类和II类HLA抗体分析。在本研究中,我们发现anti-A*24:01、anti-B*15:01和anti-C*07*01是针对hla I类抗原最常见的3种hla抗体。而anti-DRB1*11:01、anti-DQA1*05:01-DQB1*03:01和anti-DPA1*02:01-DPB1*17:01是针对hla II类抗原最常见的抗hla抗体。此外,我们的研究发现抗hla I类抗体与妊娠史之间存在显著关联。然而,在再次移植病例中,我们观察到存在针对HLA I类和II类抗原的抗体。结论:对于移植中心来说,全面了解HLA抗体的流行、MFI及其与各种致敏事件的关系是至关重要的。本研究可以极大地帮助移植社区在活体相关肾移植中选择合适的潜在器官供体、规划脱敏制度、管理受者护理和预测移植结果。
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引用次数: 0
Proliferating cell nuclear antigen (PCNA) expression and serum IL-8 product in leiomyomas. 平滑肌瘤中增殖细胞核抗原(PCNA)表达及血清IL-8产物的研究。
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-12-06 DOI: 10.1016/j.trim.2024.102160
Huda Sadoon Jassim AlBiaty, Hind H Al-Ammiri, Ali Yhea Salman

Background: The most prevalent neoplasms of the female genital tract are uterine leiomyomas, a uterine fibroid which rarely turn into cancer. We examined the levels of proliferating cell nuclear antigen (PCNA) and interleukin-8 (IL-8) in female patients with Leiomyomas.

Methods: The presence of PCNA and IL-8 were measured in 28 females with Leiomyoma and 20 healthy controls. Tissue PCNA levels were measured by immunohistochemistry (IHC) method and serum IL-8 levels were measured by an ELISA technique. Age and menopausal stage on Leiomyoma development were also examined.

Results: Forty-eight Iraqi women were divided into 28 uterine Leiomyoma patients of whom leiomyoma tissues, adjacent myometrium and serum samples were collected during hysterectomy. Serum samples were collected from 28 patients and 20 female controls. PCNA was positively expressed in 11 out of 28 (39.2 %) leiomyoma tissues; all 20 normal myometrium were negative. The presence of PCNA was unrelated to age and menopausal stage. The mean level of serum IL-8 was elevated significantly in patients (140 pg/ml) compared to that of control (60 pg/ml; P < 0.05). The IL -8 levels were increased in postmenopausal stage.

Conclusions: Each PCNA; IL-8 showed significantly elevated levels in patients with Leiomyoma.

背景:女性生殖道最常见的肿瘤是子宫平滑肌瘤,这是一种很少转变为癌症的子宫肌瘤。我们检测了女性平滑肌瘤患者的增殖细胞核抗原(PCNA)和白细胞介素-8 (IL-8)水平。方法:对28例女性平滑肌瘤患者和20例健康对照进行PCNA和IL-8的检测。采用免疫组化(IHC)法检测组织PCNA水平,ELISA法检测血清IL-8水平。年龄和绝经期对平滑肌瘤的发展也有影响。结果:48名伊拉克妇女分为子宫平滑肌瘤患者28例,在子宫切除术中采集子宫平滑肌瘤组织、邻近子宫肌层及血清样本。收集了28例患者和20例女性对照者的血清样本。28例平滑肌瘤组织中有11例(39.2% %)阳性表达PCNA;20块正常肌层均为阴性。PCNA的存在与年龄和绝经期无关。与对照组相比,患者血清IL-8平均水平(140 pg/ml)显著升高(60 pg/ml;P 结论:各PCNA;平滑肌瘤患者IL-8水平明显升高。
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引用次数: 0
Expression patterns of Galectin-3 and NLRP3 in Chagas reactivation and graft damage in heart transplants. 半凝集素-3和NLRP3在心脏移植Chagas再激活和移植物损伤中的表达模式。
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-12-05 DOI: 10.1016/j.trim.2024.102159
Caio E Gullo, Diego D Dos Santos, Mab P Corrêa, Cristiane D Gil, Reinaldo B Bestetti

Objective: This study aimed to assess the expression patterns of galectin-3 (Gal-3) and NLRP3 in heart transplant recipients according to the presence of reactivated Trypanosoma cruzi infection or allograft rejection in Chagas and non-Chagas heart transplant recipients.

Methods: Gal-3 and NLRP3 expression levels were analyzed in endomyocardial biopsies from 31 heart transplant recipients, including 16 patients with chronic Chagas disease (ChD) and 15 without ChD. Samples were evaluated during periods of graft rejection or ChD reactivation, characterized by intense myocardial cellular infiltrate, and after remission of the infiltrate, classified by histopathological severity. The transcriptional levels of genes encoding Gal-3, NLRP3, Asc, caspase-1, and IL-1β were identified using the GEO2T tool across different experimental conditions.

Results: Gal-3 expression was lower in the myocardial infiltrate of ChD patients compared to non-ChD patients (p < 0.0001), whereas NLRP3 positivity was higher in ChD patients (p < 0.05). In a murine model of T. cruzi infection, elevated Gal-3 mRNA and NLRP3 inflammasome levels were observed in myocardial interstitial cells (p < 0.05). Peripheral blood mononuclear cells and cells from rodent cardiac allografts showed increased Gal-3 mRNA and NLRP3 levels compared to non-transplanted and rodent cardiac isografts (p < 0.001).

Conclusions: Our findings suggest that Gal-3 and NLRP3 may be important biomarkers for differentiating heart transplant recipients with and without ChD regarding the myocardial immunological processes.

目的:本研究旨在评估半凝集素-3 (Gal-3)和NLRP3在恰加斯和非恰加斯心脏移植受者中根据克氏锥虫感染或同种异体移植排斥反应存在的心脏移植受者体内的表达模式。方法:分析31例心脏移植受者心肌内膜活检中Gal-3和NLRP3的表达水平,其中16例为慢性恰加斯病(ChD), 15例为非ChD。在移植排斥或冠心病再激活期间,以心肌细胞浸润为特征,在浸润缓解后,根据组织病理学严重程度对样本进行评估。使用GEO2T工具在不同实验条件下鉴定编码Gal-3、NLRP3、Asc、caspase-1和IL-1β的基因的转录水平。结果:Gal-3在冠心病患者心肌浸润中的表达低于非冠心病患者(p )结论:我们的研究结果表明,Gal-3和NLRP3可能是区分冠心病和非冠心病心脏移植受者心肌免疫过程的重要生物标志物。
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引用次数: 0
Severe SARS-CoV-2 infection is associated with increased risk of De novo HLA antibody production in lung transplant recipients: Single-center study. 严重的SARS-CoV-2感染与肺移植受者从头产生HLA抗体的风险增加相关:单中心研究
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-12-05 DOI: 10.1016/j.trim.2024.102161
Sadia Z Shah, Zeying Du, Kamal El Jack, Si M Pham, Mohamed Elrefaei

The purpose: The COVID-19 pandemic has led to significant morbidity and mortality in lung transplant recipients (LTR). Respiratory viral infections may be associated with de-novo HLA donor-specific antibody (DSA) production and impact lung transplant outcomes. Since one of the immunomodulation strategies post-SARS-CoV-2 infection in LTR include decreasing or holding anti-metabolites, concerns have been raised for higher incidence of de-novo DSA production in LTR.

Methods: We performed a retrospective chart review of 63 consecutive LTR diagnosed with COVID-19 to investigate this concern. COVID-19 disease severity was divided into 3 groups: mild, moderate, and severe. Mild disease was defined as patients with COVID-19 diagnosis who were stable enough to be treated as out-patients. Moderate disease was defined as patients who required admission to the hospital and were on less than 10 l of oxygen at rest. Severe disease was identified as patients who required hospitalization and were on more than 10 l of oxygen with or without mechanical ventilation or extra corporal membrane oxygenation (ECMO). Groups were compared using the Kruskal-Wallis test. A total of 11, 43, and 9 LTR were diagnosed with mild, moderate, and severe COVID-19 respectively.

Results: We observed no significant differences in the CPRA pre-COVID-19 compared to 1 and 6 months post-COVID-19 diagnosis in 6/11 (54.5 %), 18/43 (41.8 %), and 6/9 (66.9 %) LTR with mild (p = 0.66), moderate (p = 0.74), and severe (p = 0.22) COVID-19 respectively. HLA class I and II DSA were detected pre-COVID-19 diagnosis and persisted with no significant differences in the median MFI levels at 1 and 6 months post-COVID-19 diagnosis in 2/11 (p = 0.93), 7/43 (p = 0.71), and 0/9 LTR with mild, moderate, and severe COVID-19 respectively. De-novo HLA DSA were detected within 6 months post-COVID-19 diagnosis in 0/11 (0 %), 1/43 (2.3 %), and 3/9 (33.3 %%) LTR with mild, moderate, and severe COVID-19 respectively (p = 0.001).

Conclusion: Severe COVID-19 may be associated with increased risk of de novo HLA DSA production resulting in allograft dysfunction.

目的:COVID-19大流行导致肺移植受者(LTR)的显著发病率和死亡率。呼吸道病毒感染可能与从头生成HLA供体特异性抗体(DSA)有关,并影响肺移植结果。由于LTR感染sars - cov -2后的免疫调节策略之一包括减少或保持抗代谢物,因此LTR中重新生成DSA的发生率较高的担忧已经引起关注。方法:我们对63例连续诊断为COVID-19的LTR进行回顾性图表回顾,以调查这一担忧。将COVID-19疾病严重程度分为轻度、中度和重度3组。轻症定义为诊断为COVID-19的患者,病情稳定,可以作为门诊治疗。中度疾病被定义为需要住院并且静息时吸氧低于10 l的患者。严重疾病被确定为需要住院治疗并且在有或没有机械通气或外膜氧合(ECMO)的情况下吸氧超过10 l的患者。各组间比较采用Kruskal-Wallis检验。诊断为轻、中、重度新冠肺炎的LTR分别为11例、43例和9例。结果:我们观察到无显著差异CPRA pre-COVID-19相比1和6 月post-COVID-19诊断在6/11(54.5 %),18/43(41.8 %)和6/9(66.9 %)LTR轻度(p = 0.66),中等(p = 0.74),和严重(p = 0.22)分别COVID-19。在轻、中、重度COVID-19诊断前检测到HLA I类和II类DSA并持续存在,在2/11 (p = 0.93)、7/43 (p = 0.71)和0/9 LTR中位MFI水平分别在轻、中度和重度COVID-19诊断后1和6 个月无显著差异(p < 0.05)。轻、中、重度COVID-19患者在诊断后6个 月内分别检测到0/11(0 %)、1/43(2.3 %)和3/9(33.3% %%)LTR的De-novo HLA DSA (p = 0.001)。结论:严重的COVID-19可能与新发HLA DSA产生导致同种异体移植物功能障碍的风险增加有关。
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引用次数: 0
Plasma high-sensitivity C-reactive protein measured prior to transplant is related to prediabetes in first-year kidney transplant recipients: A single-center cross-sectional study in Vietnam 肾移植前测定的血浆高敏 C 反应蛋白与肾移植第一年受者的糖尿病前期有关:越南单中心横断面研究。
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-11-23 DOI: 10.1016/j.trim.2024.102149
Ha Nguyen Thi Thu , Dung Nguyen Thi Thuy , Thuy Pham Vu , Toan Pham Quoc , Duc Nguyen Van , Ha Do Manh , Van Diem Thi , Doan Tran Thi , Khoa Le Ha , Kien Truong Quy , Kien Nguyen Trung , Thang Le Viet

Aim

To determine the rate of prediabetes among and the pre-transplant plasma high-sensitivity C-reactive protein (hs-CRP) value predictive of prediabetes in patients during their first year post-living donor kidney transplant.

Methods

A total of 538 patients underwent living donor kidney transplantation between January 2018 and December 2020, 413 of whom met the inclusion criteria for this study. All patients underwent oral glucose tolerance tests (OGTTs) with 75 g glucose/200 mL solution, starting 3 months post-transplant and repeating the test every 3 months for the first year. Clinical and paraclinical indicators and plasma hs-CRP concentrations were quantified the day prior to the transplant. Prediabetes was diagnosed according to the American Diabetes Association 2018 criteria as a 2-h OGTT result between 140 mg/dL (7.8 mmol/L) and 199 mg/dL (11.0 mmol/L).

Results

The rate of prediabetes among the study subjects was 38.3 % (158/413). Body mass index (BMI) and pre-transplant plasma triglycerides, high-density lipoprotein cholesterol (HDLC), and hs-CRP levels were related factors predictive of prediabetes in patients within the first year post-kidney transplant based on multivariate logistic regression and receiver operative characteristic curve models. Hs-CRP was the factor with the best predictive value (area under the curve = 0.89; p < 0.001).

Conclusions

Pre-transplant plasma hs-CRP levels were a good predictor of prediabetes in the first year post-living donor kidney transplant.
目的:确定活体供肾移植术后第一年患者中糖尿病前期的发生率以及移植前血浆高敏C反应蛋白(hs-CRP)值对糖尿病前期的预测性:2018年1月至2020年12月期间,共有538名患者接受了活体肾移植,其中413人符合本研究的纳入标准。所有患者均接受了75 g葡萄糖/200 mL溶液的口服葡萄糖耐量试验(OGTT),试验从移植后3个月开始,第一年内每3个月重复一次。移植前一天对临床和辅助临床指标以及血浆 hs-CRP 浓度进行量化。根据美国糖尿病协会2018年标准,2小时OGTT结果在140毫克/分升(7.8毫摩尔/升)和199毫克/分升(11.0毫摩尔/升)之间即可诊断为糖尿病前期:研究对象中糖尿病前期的比例为 38.3%(158/413)。根据多变量逻辑回归和受体操作特征曲线模型,身体质量指数(BMI)和移植前血浆甘油三酯、高密度脂蛋白胆固醇(HDLC)和hs-CRP水平是预测肾移植后第一年内患者糖尿病前期的相关因素。Hs-CRP 是具有最佳预测价值的因素(曲线下面积 = 0.89;p 结论:Hs-CRP 是肾移植后第一年内预测糖尿病前期的相关因素:移植前血浆hs-CRP水平是活体肾移植后第一年内糖尿病前期的良好预测因子。
{"title":"Plasma high-sensitivity C-reactive protein measured prior to transplant is related to prediabetes in first-year kidney transplant recipients: A single-center cross-sectional study in Vietnam","authors":"Ha Nguyen Thi Thu ,&nbsp;Dung Nguyen Thi Thuy ,&nbsp;Thuy Pham Vu ,&nbsp;Toan Pham Quoc ,&nbsp;Duc Nguyen Van ,&nbsp;Ha Do Manh ,&nbsp;Van Diem Thi ,&nbsp;Doan Tran Thi ,&nbsp;Khoa Le Ha ,&nbsp;Kien Truong Quy ,&nbsp;Kien Nguyen Trung ,&nbsp;Thang Le Viet","doi":"10.1016/j.trim.2024.102149","DOIUrl":"10.1016/j.trim.2024.102149","url":null,"abstract":"<div><h3>Aim</h3><div>To determine the rate of prediabetes among and the pre-transplant plasma high-sensitivity C-reactive protein (hs-CRP) value predictive of prediabetes in patients during their first year post-living donor kidney transplant.</div></div><div><h3>Methods</h3><div>A total of 538 patients underwent living donor kidney transplantation between January 2018 and December 2020, 413 of whom met the inclusion criteria for this study. All patients underwent oral glucose tolerance tests (OGTTs) with 75 g glucose/200 mL solution, starting 3 months post-transplant and repeating the test every 3 months for the first year. Clinical and paraclinical indicators and plasma hs-CRP concentrations were quantified the day prior to the transplant. Prediabetes was diagnosed according to the American Diabetes Association 2018 criteria as a 2-h OGTT result between 140 mg/dL (7.8 mmol/L) and 199 mg/dL (11.0 mmol/L).</div></div><div><h3>Results</h3><div>The rate of prediabetes among the study subjects was 38.3 % (158/413). Body mass index (BMI) and pre-transplant plasma triglycerides, high-density lipoprotein cholesterol (HDL<img>C), and hs-CRP levels were related factors predictive of prediabetes in patients within the first year post-kidney transplant based on multivariate logistic regression and receiver operative characteristic curve models. Hs-CRP was the factor with the best predictive value (area under the curve = 0.89; <em>p</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Pre-transplant plasma hs-CRP levels were a good predictor of prediabetes in the first year post-living donor kidney transplant.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"88 ","pages":"Article 102149"},"PeriodicalIF":1.6,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717283","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}
引用次数: 0
Utilization of kidneys from tuberculosis-infected donors in renal transplantation: A case report 在肾移植中利用结核病感染供体的肾脏:病例报告。
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-11-20 DOI: 10.1016/j.trim.2024.102151
Lu Yifan , Liu Yiting , Zhou Jiangqiao , Qiu Tao
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.
在结核病流行的国家,实体器官移植中的结核病(TB)感染是一个不容忽视的问题,现有的指南都不建议使用活动性结核病感染者的器官。在这里,我们描述了本中心在肾移植中使用结核病感染供体肾脏的三个病例,其中两人患有活动性结核病。在这三个病例中,所有受者的移植功能良好,在 1-4 年的随访期间 TST 结果均为阴性。本病例报告强调了结核病的早期诊断、预防和治疗在肾移植中的关键作用,展示了利用活动性结核病供体肾脏的潜力,为实体器官移植开辟了新的可能性。
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引用次数: 0
Clinical characteristics and outcomes of invasive pulmonary aspergillosis in renal transplant recipients: A single-center experience 肾移植受者侵袭性肺曲霉菌病的临床特征和预后:单中心经验
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-11-20 DOI: 10.1016/j.trim.2024.102150
Jilin Zou, Zeya Jin

Objective

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).

Methods

We retrospectively examined 22 patients who were diagnosed with IPA post-RT and treated at our institution between 2005 and 2024.

Results

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.

Conclusions

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.
目的本研究旨在探讨肾移植(RT)后患者侵袭性肺曲霉菌病(IPA)的临床特征、早期诊断方法和治疗方法:我们回顾性研究了 2005 年至 2024 年期间在我院接受治疗的 22 例肾移植术后确诊为 IPA 的患者:患者平均年龄为(46.4±9.4)岁,男性占多数(72.7%)。RT后IPA的发生率为1.29%。移植后出现IPA的中位时间为12个月。发热是主要症状(72.7%),其次是咳嗽和痰多(31.8%)和咯血(13.6%)。常见的计算机断层扫描结果包括合并症(68.2%)和空洞(45.5%),并伴有光晕征、多发结节和气新月征。五名患者出现中性粒细胞减少,其中一例出现粒细胞减少。59.1%的患者肾功能受损。45.5%的患者血清1,3-β-D-葡聚糖和半乳甘露聚糖(GM)检测呈阳性,83.3%的患者支气管肺泡灌洗液GM检测证实为IPA。下一代测序证实 11 名患者感染了曲霉菌。最终,68.2%的患者痊愈,31.8%的患者因感染而死亡,死亡患者的并发症发生率明显较高:结论:IPA患者的死亡率很高。结论:IPA 患者的死亡率很高。RT 后的 IPA 症状通常没有特异性,因此诊断非常困难。事实证明,支气管肺泡灌洗液 GM 检测和下一代测序作为 IPA 的检测方法相对有用。应尽快开始抗真菌治疗,以避免并发症。
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引用次数: 0
Cyclosporine: Immunosuppressive effects, entwined toxicity, and clinical modulations of an organ transplant drug 环孢素的免疫抑制作用、纠缠不清的毒性以及器官移植药物的临床调整。
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-11-15 DOI: 10.1016/j.trim.2024.102147
Razan Alqadi , Amal Alqumia , Ibrahim S. Alhomoud , Ahmad Alhowail , Maha Aldubayan , Hamdoon A. Mohammed , Hussam Alhmoud , Riaz A. Khan
The discovery and use of cyclosporine since its inception into the clinics in the ‘70s and up have played a crucial role in advancing transplant therapy, and containment of the immune-based rejections. The drug has improved the high rates of acute rejections and has supported early graft survival. However, the long-term survival of renal allografts is still less prevalent, and an in-depth analysis, as well as reported findings led us to believe that there is a chronic irreversible component to the drug, that is tackled through its metabolites, and that causes toxicity, which has led to new therapies, including monoclonal antibody-based medications. A recap of the immunosuppressive effects, and entwined toxicity of the drug, now relegated primarily to bone marrow early transplants, is being overviewed for the past protocols that were used to minimize, and avoid, or use this calcineurin inhibitor class of drug, cyclosporine, in combination 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 developments. The review also attempts to find conclusive strategies reported in the 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, need for administration of oxygen, and avoiding the administration of drugs, that increase the blood levels of the cyclosporine, are beneficial interventions, when encountering cyclosporine toxicity cases. The constrained therapeutic outcomes have also led to redesign, and making use of combined formulations to reassess the pharmacokinetics of the drug.
自上世纪 70 年代环孢素进入临床以来,它的发现和使用在促进移植治疗和控制免疫排斥方面发挥了至关重要的作用。这种药物提高了急性排斥反应的发生率,并有助于早期移植的存活。然而,肾脏同种异体移植的长期存活率仍然较低,深入的分析和报告结果让我们相信,这种药物存在一种慢性不可逆成分,通过其代谢物来解决,并导致毒性,从而产生了新的疗法,包括基于单克隆抗体的药物。回顾一下这种药物的免疫抑制作用和缠绕在一起的毒性,现在这种药物已不再用于实体移植,综述了过去用于尽量减少和避免这种降钙素抑制剂类药物或与其他药物联合使用的方案。本综述回避了环孢素的作用机制、病理生理学、细胞色素的作用以及与急性和慢性毒性相关的其他因素。它还试图找到近期研究中报道的避免其毒副作用的确凿策略,并制定该药物的安全使用策略。在遇到环孢素中毒病例时,胃肠道净化、支持呼吸道、监测呼吸功能不全的迹象、监测严重反应(如癫痫发作)、给氧以及避免使用会增加环孢素血药浓度的药物都是有益的干预措施。受限的治疗效果也促使人们重新设计和组合配方,以审查药物的药代动力学。
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引用次数: 0
Identification of mitophagy-related gene signatures for predicting delayed graft function and renal allograft loss post-kidney transplantation 鉴定与有丝分裂相关的基因特征,以预测肾移植后移植功能延迟和肾异体移植损失。
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-11-14 DOI: 10.1016/j.trim.2024.102148
Kaifeng Mao , Fenwang Lin , Yige Pan , Zhenquan Lu , Bingfeng Luo , Yifei Zhu , Jiaqi Fang , Junsheng Ye

Background

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.

Methods

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.

Results

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.

Conclusions

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.
背景:缺血再灌注损伤(IRI)是肾移植术后不可避免的后果,它不可避免地会导致肾脏损伤。大量研究表明,有丝分裂与人类癌症有关。然而,人们对有丝分裂在肾移植中的功能仍知之甚少。本研究旨在开发有丝分裂相关基因(MRGs)特征,以预测肾移植后移植功能延迟(DGF)和肾移植损失:方法:对差异表达基因(DEGs)进行鉴定,并与MRGs交叉,得到有丝分裂相关DEGs(MRDEGs)。进行了功能富集分析。随后,采用随机森林和 SVM-RFE 机器学习来识别枢纽基因。利用 LASSO 回归分析构建了 DGF 诊断预测特征。肾移植预后预测特征是通过单变量 Cox 和 LASSO 回归分析建立的。此外,还进行了ROC曲线、免疫学特征、相关性分析和生存分析:结果:通过将 61 个 DEG 与 4897 个 MRG 相交,得到了 19 个 MRDEG。然后通过机器学习确定了七个中心基因。随后,建立了五基因 DGF 诊断预测特征,ROC 曲线显示其对 DGF 具有很高的诊断价值。免疫浸润分析表明,与即刻移植物功能(IGF)组相比,DGF 组的许多免疫细胞更为丰富。研究还发现了一种双基因预后特征,它能准确预测肾异体移植物的预后:有丝分裂相关基因特征对 DGF 和肾脏同种异体移植物丢失具有很高的预测准确性。我们的研究可为肾移植后的预后和治疗策略提供新的视角。
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引用次数: 0
Potential of new 250-nautical mile concentric circle allocation system for improving the donor/recipient HLA matching: Development of new matching algorithm 新的 250 海里同心圆分配系统改善供体/受体 HLA 匹配的潜力:开发新的匹配算法。
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-11-12 DOI: 10.1016/j.trim.2024.102146
Fayeq Jeelani Syed , Dulat Bekbolsynov , Robert C. Green II , Devinder Kaur , Obi Ekwenna , Puneet Sindhwani , Michael Rees , Stanislaw Stepkowski

Background

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.

Methods

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.

Results

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.

Conclusion

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.
背景:人类白细胞抗原(HLA)的高分辨率分型可通过选择低免疫原性移植物彻底改变肾移植领域。方法:使用内部开发的模拟算法,将 2015 年至 2019 年期间托莱多大学医学中心(UTMC)在移植受者科学登记处(SRTR)登记的 501 名移植候选者与 250 海里范围内采购的 4812 名供者进行虚拟匹配。根据估算的高分辨率 HLA,测量了 HMS(疏水错配得分)≤10 的免疫原性。将 KDPI≤50% 的模拟 "最佳 "配型与 2000 年至 2010 年间的移植队列及其肾移植存活率进行了比较:结果:在 501 例受者中,有 500 例(99.8%)与 HMS 值小于 10 且 KDPI 小于 50 % 的供体匹配。模拟移植的 HMS 平均值为 1.4(范围为 0-10),而回顾性队列的 HMS 平均值为 6.3(范围为 0-75)(p 结论:模拟移植的 HMS 平均值为 1.4(范围为 0-10),而回顾性队列的 HMS 平均值为 6.3(范围为 0-75):250 海里范围内的捐献者为UTMC 患者寻找匹配度高的低免疫原性 HLA 肾脏捐献者提供了多种选择,从而大大提高了他们长期异体移植存活的机会。
{"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 ,&nbsp;Dulat Bekbolsynov ,&nbsp;Robert C. Green II ,&nbsp;Devinder Kaur ,&nbsp;Obi Ekwenna ,&nbsp;Puneet Sindhwani ,&nbsp;Michael Rees ,&nbsp;Stanislaw Stepkowski","doi":"10.1016/j.trim.2024.102146","DOIUrl":"10.1016/j.trim.2024.102146","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 (<em>p</em> &lt; 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 (<em>p</em> &lt; 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 &lt; 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 &lt; 10; range 8–378). Similar values were found for patients between 2015 and 2019.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Transplant immunology
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