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Association of PIRCHE-II score with anti-donor T-cell response and risk of de novo donor-specific antibody production in kidney transplant recipients 肾移植受者的 PIRCHE-II 评分与抗供体 T 细胞反应和新的供体特异性抗体产生风险的关系。
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-11-03 DOI: 10.1016/j.trim.2024.102145
Hiroaki Yamane, Kentaro Ide, Yuka Tanaka, Masahiro Ohira, Hiroyuki Tahara, Seiichi Shimizu, Hiroshi Sakai, Ryosuke Nakano, Hideki Ohdan

Background

De novo 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.

Methods

Data of 105 adult living-donor KT recipients were retrospectively assessed.

Results

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.

Conclusions

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.
背景:新的供体特异性抗体(dnDSAs)会影响肾移植(KT)的长期预后。较高的预测间接再识别人类白细胞抗原(HLA)表位(PIRCHE-II)得分与各种临床结果相关,包括dnDSA的形成。然而,目前还缺乏对 PIRCHE-II 评分与抗供体 T 细胞反应之间关系的详细分析。因此,本研究调查了与 dnDSA 形成相关的 PIRCHE-II 评分与抗供体 T 细胞反应的混合淋巴细胞反应结果之间的关系:方法:回顾性评估了105例成年活体KT受者的数据:结果:在105名患者中,13.3%在观察期间出现了dnDSAs。HLA-DQ 位点的 PIRCHE-II 评分(PIRCHE-DQ)在形成 dnDSA 的患者中明显高于未形成 dnDSA 的患者。PIRCHE-DQ≥77 组的 dnDSA 形成率明显高于 PIRCHE-DQ 结论:PIRCHE-DQ可预测dnDSA的形成和抗供体T细胞反应。在 PIRCHE-DQ 偏高的情况下,减少免疫抑制药物的剂量可能并非明智之举。
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引用次数: 0
A betaine-contained solution reduced cold ischemia damage through inhibiting vacuolar degeneration in livers 含甜菜碱的溶液通过抑制肝脏空泡变性减轻了冷缺血损伤。
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-11-02 DOI: 10.1016/j.trim.2024.102144
Yu Wang , Tingting Lan , Shao-Hua Wu , Jiangong Ma , Xunfeng Zou
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 (H2O2) in hepatocytes was examined. Liver damage was significantly reduced in the UW and MS groups (p < 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 H2O2 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 H2O2 accumulation.
本研究配制了一种新的含多种糖(MS)的渗透保护剂溶液。主要目的是比较MS溶液与威斯康星大学(UW)溶液和高渗柠檬酸腺嘌呤(HCA)溶液对肝脏冷保存的影响,并研究渗透压诱导损伤的机制。使用不同的溶液将大鼠肝脏在4 °C下冷藏18小时,然后进行2小时的常温机器灌注(NMP)以评估其功能。肝脏被分为四组:HCA 组、UW 组、MS 组和对照组。在进行组织病理学分析的同时,还使用乳酸脱氢酶(LDH)等生化指标对肝功能和组织学变化进行评估。此外,还检测了肝细胞中水汽素 9 (AQP9) 和过氧化氢 (H2O2) 的表达。华大组和 MS 组的肝损伤明显减轻(p 2O2 荧光强度和肝脏空泡变性中 AQP9 蛋白水平降低)。总之,MS 溶液通过抑制细胞内 H2O2 积累引起的液泡变性,在冷藏期间保存肝脏方面表现出卓越的功效。
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引用次数: 0
Kidney transplantation after ABO-incompatible hematopoietic stem cell transplantation: A case report and literature review ABO不相容造血干细胞移植后的肾移植:病例报告和文献综述。
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-11-02 DOI: 10.1016/j.trim.2024.102143
Kazuro Kikkawa, Masahiro Tamaki, Kouhei Maruno, Tatsuya Hazama, Toshifumi Takahashi, Yuya Yamada, Masakazu Nakashima, Noriyuki Ito
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.
尽管一些研究报告了造血干细胞移植后终末期肾病的肾移植,但很少有报告称ABO不相容造血干细胞移植后进行了肾移植。在本报告中,我们描述了一例大样本ABO不相容造血干细胞移植后的肾移植病例,并回顾了以往关于造血干细胞移植后肾移植的报道。一名21岁的男性患者因患B淋巴细胞淋巴瘤接受了非亲缘供者的ABO不相容造血干细胞移植。由于药物毒性,他患上了慢性肾病,需要接受肾脏替代治疗,并在标准免疫抑制下接受了来自其母亲的ABO相容活体肾移植。肾移植前,他没有抗供体血型抗体。肾移植 10 个月后,他的临床状况良好,肾功能良好。已有 84 例造血干细胞移植后肾移植的文献报道。其中 25 例受者与造血干细胞移植的供体相同。在这 25 名受者中,有 15 人没有接受维持性免疫抑制治疗。排斥反应发生率低(14%),感染率(32%)和恶性肿瘤发生率(10%)高,这表明造血干细胞移植后的肾移植受者免疫抑制过度。包括本病例在内,仅有三篇关于 ABO 不相容造血干细胞移植后进行肾移植的报道。肾移植可能是造血干细胞移植后终末期肾病的有效肾脏替代疗法,即使在ABO血型不相容的造血干细胞移植病例中也是如此。
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引用次数: 0
Impact of renal allograft histopathological findings on transplant patient outcomes and graft survival: A retrospective single-center study 肾移植组织病理学结果对移植患者预后和移植物存活率的影响:一项回顾性单中心研究。
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-10-28 DOI: 10.1016/j.trim.2024.102142
Tiago Xavier Silva , Evaldo Nascimento , Marcelo Gonçalves de Oliveira , Raquel A. Fabreti-Oliveira

Introduction

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 de novo donor-specific antibodies (DSA).

Methods

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.

Results

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 de novo 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 de novo DSA and non-DSA groups from the third (p = 0.039), fifth (p = 0.028), and seventh years of follow-up (p = 0.012). The graft survival rate was lower in patients with de novo DSA than in those without (p = 0.036).

Conclusions

TCMR and AMR were the most common findings. The occurrence of AMR significantly impacted renal function and graft survival, and patients with de novo anti-HLA antibodies had poorer outcomes.
简介本研究旨在通过分析异体移植物活检结果,评估肾移植功能障碍的原因。我们还比较了有和没有新的供体特异性抗体(DSA)患者的临床结果和移植物存活率:这项回顾性观察队列研究包括79名接受肾脏同种异体移植活检的患者。根据抗人类白细胞抗原(HLA)DSA抗体的存在情况将患者分为两组。实验室评估包括 HLA-DSA 和血清肌酐水平。免疫抑制治疗方案如下:单抗原珠测出致敏(面板反应性抗体>50%)的患者接受诱导治疗,所有患者接受他克莫司或环孢素、泼尼松和霉酚酸钠三联疗法:结果:20.2%的患者出现了急性抗体介导的排斥反应(AMR),14%的患者出现了急性T细胞介导的排斥反应(TCMR)。新发DSA患者中分别有53.8%和69.2%出现间质纤维化和肾小管萎缩,而非DSA组分别为15.2%和87.9%。降钙素抑制剂引起肾毒性的占 11.4%,引起基础疾病复发的占 13.9%,引起感染的占活检的 7.6%。在随访的第三年(p = 0.039)、第五年(p = 0.028)和第七年(p = 0.012),观察到新生 DSA 组和非 DSA 组的血清肌酐水平存在差异。新发DSA患者的移植物存活率低于非DSA患者(p = 0.036):结论:TCMR和AMR是最常见的发现。结论:TCMR和AMR是最常见的发现,AMR的发生严重影响了肾功能和移植物存活率,而有新的抗HLA抗体的患者预后较差。
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引用次数: 0
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 活化 T 细胞胞浆核因子 1(NFATc1)插入基因多态性可能是肾移植后急性 T 细胞介导的排斥反应(aTCMR)的诱因。
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-10-24 DOI: 10.1016/j.trim.2024.102139
Yisheng Ji , Congcong Chen , Pei Lu , Zijie Wang , Hao Chen , Li Sun , Shuang Fei , Xiaobing Ju , Ruoyun Tan , Min Gu

Background

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.

Methods

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.

Results

NFATc1 rs55741427 insertion was identified to be significantly associated with the post-surgery aTCMR(OR = 2.66, P < 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 (P = 0.0048).

Conclusion

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.
背景:研究基因插入或缺失(in/del)多态性对肾移植后急性T细胞介导的排斥反应(aTCMR)发生的潜在调控作用:研究基因插入或缺失(in/del)多态性对肾移植术后急性T细胞介导的排斥反应(aTCMR)发生的潜在调控作用:我们回顾性分析了2010年2月1日至2015年12月1日期间在南京医科大学第一附属医院接受肾移植手术的133名受者的5年随访数据。通过基于下一代测序(NGS)的目标测序,计算哈代-温伯格平衡(HWE)、小等位基因频率(MAF)和连锁不平衡(LD)区块,从而选择标签in/dels。与 aTCMR 相关的重要 in/dels 是通过临床共因子协方差分析 (ANCOVA) 和使用 "SNPassoc "软件包在 Rstudio 中进行的模型分析得出的交叉结果确定的。此外,还采用了逻辑模型来评估基因型与术后 5 年内 aTCMR 发生率之间的关联:结果:发现 NFATc1 rs55741427 插入与术后 aTCMR 有显著相关性(OR = 2.66,P 结论:NFATc1 rs55741427 插入突变与术后 aTCMR 有显著相关性:研究发现,rs55741427的插入突变与手术后5年随访期间的aTCMR具有统计学相关性。我们的模型发现,DGF 和 rs55741427 插入突变是与 aTCMR 相关的两个关键危险因素,aTCMR 高危人群的移植物预后较差。
{"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 ,&nbsp;Congcong Chen ,&nbsp;Pei Lu ,&nbsp;Zijie Wang ,&nbsp;Hao Chen ,&nbsp;Li Sun ,&nbsp;Shuang Fei ,&nbsp;Xiaobing Ju ,&nbsp;Ruoyun Tan ,&nbsp;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> &lt; 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}
引用次数: 0
Hepatic draining lymph nodes in human liver transplant: Implications in alloimmunity and tolerance 人类肝移植中的肝引流淋巴结:异体免疫和耐受的意义
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-10-22 DOI: 10.1016/j.trim.2024.102140
Mohamed I. Mohamed , Mattias Embretsen , Justin H. Nguyen

Background

Hepatic draining lymph nodes (HDLN) are implicated in allograft alloimmunity and tolerance. In contrast to experimental work, the role of HDLNs in human liver transplant (LT) is unknown due to lack of relevant clinical tissue.

Methods

During LT, the porta hepatis was dissected near the liver hilum during native hepatectomy. The HDLN in this region was taken prior to reperfusion (prereperfusion). Following complete reperfusion with recipient portal venous blood, hepatic arterial inflow into the allograft was established. As the recipient's common hepatic artery was fully mobilized, its HDLNs were removed and submitted to pathology (postreperfusion).

Results

Of 37 LTs performed between January 1, 2021, and July 9, 2022, 20 had both pre- and postreperfusion HDLNs archived (Group A); 11 had only postreperfusion HDLNs archived (Group B), and 6 had no archived HDLNs (Group C). Removing and archiving HDLNs did not increase operative times or transfusion requirements. For groups A, B, and C, mean (SD) warm ischemic times were 25.2 (2.0), 25.3 (3.2), and 28.3 (6.2) minutes, respectively (P > .05); operating times were 3.9 (0.7), 6.9 (7.8), and 7.9 (7.1) hours, respectively (A vs C, P = .017; C vs B, P > .05); and units of transfused packed red blood cells were 8.0 (3.8), 11.1 (10.3), and 12.2 (7.6), respectively (P > .05).

Conclusion

We describe an approach for clinical archiving of HDLNs obtained within the operative field during orthotopic LT in humans. Availability of relevant HDLNs is essential for investigations of primary immune responses potentially important in allograft alloimmunity and tolerance.
背景:肝引流淋巴结(HDLN)与同种异体免疫和耐受有关。与实验研究相反,由于缺乏相关的临床组织,HDLN 在人类肝移植(LT)中的作用尚不清楚:方法:在肝移植过程中,原发性肝切除术在肝门附近切除肝门。方法:肝移植过程中,在原肝切除术中解剖肝门附近,在再灌注(再灌注前)前提取该区域的高密度脂蛋白。用受体门静脉血液进行完全再灌注后,肝动脉血流入异体移植物。随着受体肝总动脉的完全活动,其高密度脂蛋白网被移除并提交病理检查(再灌注后):结果:在2021年1月1日至2022年7月9日期间进行的37例LT手术中,20例在再灌注前和再灌注后均有HDLN存档(A组);11例仅有再灌注后的HDLN存档(B组);6例无HDLN存档(C组)。移除和存档 HDLN 不会增加手术时间或输血需求。A 组、B 组和 C 组的平均(标清)温暖缺血时间分别为 25.2 (2.0)、25.3 (3.2) 和 28.3 (6.2) 分钟(P > .05);手术时间分别为 3.9 (0.7)、6.9 (7.8) 和 7.9 (7. 1) 小时(A 组 vs. B 组)。1)小时(A vs C,P = .017;C vs B,P > .05);输注包装红细胞的单位分别为 8.0 (3.8)、11.1 (10.3) 和 12.2 (7.6)(P > .05):我们描述了一种在人体正位LT过程中在手术区域内获得的HDLN的临床存档方法。获得相关的 HDLNs 对于研究可能对异体移植物同种免疫和耐受性很重要的原发性免疫反应至关重要。
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引用次数: 0
Outcomes with chimeric antigen receptor T-cell therapy in Rheumatological disorders: A systematic review 风湿病嵌合抗原受体 T 细胞疗法的疗效:系统综述。
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-10-21 DOI: 10.1016/j.trim.2024.102137
Fizza Zulfiqar , Moazzam Shahzad , Muhammad Kashif Amin , Abhinav Vyas , Zouina Sarfraz , Anika Zainab , Hana Qasim , Dania Kaur , Naghmeh Khavandgar , Forat Lutfi , Peiman Hematti , Joseph P. McGuirk , Muhammad Umair Mushtaq

Background

Chimeric antigen receptor T cell (CAR-T) therapy is an emerging form of immunotherapy that has recently gained recognition for treating hematological malignancies. This successful utilization of CAR-T therapy has attracted interest in its application in refractory rheumatological diseases. Here, we will review the use of CAR-T therapy in rheumatological diseases.

Methods

Per PRISMA guidelines, a comprehensive literature search was performed on PubMed, Cochrane, and ClinicalTrials.gov using keywords for ‘CAR-T cell therapy’ and ‘Rheumatological diseases’ from inception to December 9, 2023. After screening 2977 articles, six studies reporting outcomes of CAR-T cell therapies in patients with underlying autoimmune /rheumatological diseases. Descriptive analysis was performed to represent demographics and clinical outcomes.

Results

A total of 101 adult patients from six studies were included in this systematic review. The median age of the participants was 50.8 years (IQR: 14.875), with ages ranging from 18 to 83 years. The included studies comprised 2 case reports, 1 case series, one observational study, and two clinical trials. The studies were conducted globally, including USA, Germany, and China. The underlying rheumatologic conditions were systemic lupus erythematosus (17.8 %), rheumatoid arthritis (23.8 %), myasthenia gravis (13.8 %), neuromyelitis optica (11.9 %), and others (32.7 %). The target of CAR-T therapy included CD-19 in four studies and B cell maturation antigen (BCMA) in two studies. All the patients were on prior therapy, including glucocorticoids and disease-modifying antirheumatic drugs. Follow-up ranged from a month to 1.5 years. Most of the studies reported improvement in the symptoms and decline in serological biomarkers of the underlying disease. The notable outcomes in the included studies were a 100 % response rate in five out of six studies. Grade 1 and 2 cytokine release syndrome (CRS) was observed in five studies. Only one study reported Grade 3 or higher CRS. 2 patients (1.98 %) developed neurotoxicity among the adverse effects.

Conclusion

CAR-T cell therapy is a paradigm shift in managing rheumatologic diseases, with symptomatic improvement and biochemical control of these diseases. Although preliminary evidence indicates promising results, long-term follow-up and prospective clinical trials are needed to establish optimal timing and assess the safety and efficacy of CAR-T immunotherapy.
背景:嵌合抗原受体 T 细胞(CAR-T)疗法是一种新兴的免疫疗法,最近在治疗血液恶性肿瘤方面获得了认可。CAR-T 疗法的成功应用引起了人们对其在难治性风湿病中应用的兴趣。在此,我们将回顾 CAR-T 疗法在风湿病中的应用:根据 PRISMA 指南,我们在 PubMed、Cochrane 和 ClinicalTrials.gov 上使用 "CAR-T 细胞疗法 "和 "风湿病 "关键词进行了全面的文献检索,检索时间从开始到 2023 年 12 月 9 日。在筛选了 2977 篇文章后,有六项研究报告了 CAR-T 细胞疗法在自身免疫/风湿病患者中的疗效。对人口统计学和临床结果进行了描述性分析:本系统综述共纳入了六项研究中的 101 名成年患者。参与者的中位年龄为 50.8 岁(IQR:14.875),年龄从 18 岁到 83 岁不等。纳入的研究包括 2 个病例报告、1 个系列病例、1 个观察性研究和 2 个临床试验。这些研究在全球范围内进行,包括美国、德国和中国。基础风湿病包括系统性红斑狼疮(17.8%)、类风湿性关节炎(23.8%)、重症肌无力(13.8%)、神经脊髓炎(11.9%)和其他(32.7%)。四项研究的CAR-T疗法靶点包括CD-19,两项研究的靶点包括B细胞成熟抗原(BCMA)。所有患者之前都接受过治疗,包括糖皮质激素和改善病情抗风湿药物。随访时间从一个月到 1.5 年不等。大多数研究报告称,患者的症状有所改善,潜在疾病的血清生物标志物有所下降。所纳入研究的显著结果是,六项研究中有五项的应答率达到 100%。五项研究观察到 1 级和 2 级细胞因子释放综合征(CRS)。只有一项研究报告了 3 级或以上的 CRS。2名患者(1.98%)出现了神经毒性等不良反应:结论:CAR-T 细胞疗法是治疗风湿病的一种范式转变,可改善症状并控制这些疾病的生化指标。尽管初步证据显示效果良好,但仍需要长期随访和前瞻性临床试验来确定最佳时机,并评估 CAR-T 免疫疗法的安全性和有效性。
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引用次数: 0
Institutional insights into engraftment syndrome: A cohort study on allogeneic transplantation outcomes 机构对移植综合征的见解:关于同种异体移植结果的队列研究。
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-10-21 DOI: 10.1016/j.trim.2024.102141
Júlia Plentz Portich , Aline Sinhorelo Ribeiro , Lisandra Della Costa Rigoni , Lúcia Mariano da Rocha Silla , Claudia Caceres Astigarraga , Liane Esteves Daudt , Alessandra Aparecida Paz

Background

Engraftment syndrome (ES) is a clinical condition that may occur during neutrophil recovery after hematopoietic stem cell transplantation (HSCT). Diagnosis is challenging because of the varying diagnostic criteria and the controversial relationship between ES and graft-versus-host disease (GVHD).

Objective

To investigate the incidence of ES and its relationship with GVHD in patients undergoing allogeneic HSCT at our institution.

Study design

This retrospective cohort study included patients who underwent allogeneic HSCT (alloHSCT) at a Brazilian tertiary hospital between January 2015 and December 2016. ES was diagnosed based on the Spitzer or Maiolino criteria.

Results

Of the 79 patients who underwent alloHSCT, three presented with graft failure and were excluded from the analysis. The incidence of ES, according to both Spitzer's and Maiolino's criteria, was 16.5 % and 9.8 % in patients older than 14 years and 28.6 % in children, respectively, with a significant correlation (P < 0.05, Pearson's chi-squared test). ES was associated with prolonged hospitalization (P = 0.01; Student's t-test). No correlation was observed between acute GVHD and ES. There was a positive correlation between the use of broad-spectrum antibiotics against multidrug-resistant bacteria and ES development (P < 0.05, Pearson's chi-squared test).

Conclusions

The general incidence of ES in this cohort was consistent with that reported in the literature. Remarkably, ES was associated with prolonged hospitalization (14 days longer than in patients without ES). Moreover, patients who used antibiotics against multidrug-resistant bacteria had a higher incidence of ES.
背景:移植综合征(ES)是造血干细胞移植(HSCT)后中性粒细胞恢复期间可能出现的一种临床症状。由于诊断标准不一,且ES与移植物抗宿主疾病(GVHD)之间的关系存在争议,因此诊断具有挑战性:研究设计:这项回顾性队列研究纳入了2015年1月至2016年12月期间在巴西一家三级医院接受异基因造血干细胞移植(alloHSCT)的患者。ES根据Spitzer或Maiolino标准进行诊断:在接受同种异体造血干细胞移植的79名患者中,有3人出现移植失败,被排除在分析之外。根据Spitzer和Maiolino的标准,14岁以上患者的ES发生率分别为16.5%和9.8%,儿童患者的ES发生率为28.6%,两者之间存在显著相关性(P 结论:ES的发生率与移植失败率之间存在显著相关性:本组人群中 ES 的总体发病率与文献报道一致。值得注意的是,ES 与住院时间延长有关(比没有 ES 的患者多住院 14 天)。此外,使用抗生素治疗耐多药细菌的患者 ES 发生率更高。
{"title":"Institutional insights into engraftment syndrome: A cohort study on allogeneic transplantation outcomes","authors":"Júlia Plentz Portich ,&nbsp;Aline Sinhorelo Ribeiro ,&nbsp;Lisandra Della Costa Rigoni ,&nbsp;Lúcia Mariano da Rocha Silla ,&nbsp;Claudia Caceres Astigarraga ,&nbsp;Liane Esteves Daudt ,&nbsp;Alessandra Aparecida Paz","doi":"10.1016/j.trim.2024.102141","DOIUrl":"10.1016/j.trim.2024.102141","url":null,"abstract":"<div><h3>Background</h3><div>Engraftment syndrome (ES) is a clinical condition that may occur during neutrophil recovery after hematopoietic stem cell transplantation (HSCT). Diagnosis is challenging because of the varying diagnostic criteria and the controversial relationship between ES and graft-versus-host disease (GVHD).</div></div><div><h3>Objective</h3><div>To investigate the incidence of ES and its relationship with GVHD in patients undergoing allogeneic HSCT at our institution.</div></div><div><h3>Study design</h3><div>This retrospective cohort study included patients who underwent allogeneic HSCT (alloHSCT) at a Brazilian tertiary hospital between January 2015 and December 2016. ES was diagnosed based on the Spitzer or Maiolino criteria.</div></div><div><h3>Results</h3><div>Of the 79 patients who underwent alloHSCT, three presented with graft failure and were excluded from the analysis. The incidence of ES, according to both Spitzer's and Maiolino's criteria, was 16.5 % and 9.8 % in patients older than 14 years and 28.6 % in children, respectively, with a significant correlation (<em>P</em> &lt; 0.05, Pearson's chi-squared test). ES was associated with prolonged hospitalization (<em>P</em> = 0.01; Student's <em>t</em>-test). No correlation was observed between acute GVHD and ES. There was a positive correlation between the use of broad-spectrum antibiotics against multidrug-resistant bacteria and ES development (<em>P</em> &lt; 0.05, Pearson's chi-squared test).</div></div><div><h3>Conclusions</h3><div>The general incidence of ES in this cohort was consistent with that reported in the literature. Remarkably, ES was associated with prolonged hospitalization (14 days longer than in patients without ES). Moreover, patients who used antibiotics against multidrug-resistant bacteria had a higher incidence of ES.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 102141"},"PeriodicalIF":1.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508758","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
Allogeneic abdominal non-vascularized rectus fascia transplantation without immunosuppression equals syngeneic transplantation in a rabbit model at short-term follow-up 在兔子模型中,无免疫抑制的异体腹部无血管直肌筋膜移植在短期随访中与同种异体移植效果相当。
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-10-21 DOI: 10.1016/j.trim.2024.102138
Nele Van De Winkel , Marina Gabriela M.C. Mori da Cunha , Antoine Dubois , Ewout Muylle , Lisanne Terrie , Ina Hennion , Gert De Hertogh , Heleen Fehervary , Lieven Thorrez , Marc Miserez , Jacques Pirenne , André D’Hoore , Laurens J. Ceulemans
Complex abdominal wall repair remains a major surgical challenge. In transplant patients, non-vascularized rectus fascia (NVRF) is successfully used to bridge the defect. To extrapolate this to non-transplant patients, we developed a rabbit model of NVRF-transplantation without immunosuppression comparing syngeneic versus allogeneic transplants. Short-term outcome (4 weeks) was evaluated macroscopically (ingrowth, seroma/hematoma, herniation, and infection), histologically at the graft interface and center (inflammation, neovascularization, and collagen deposition) and by mechanical testing. In both groups a similar macroscopic ingrowth of the NVRF was observed. In the syn-group, one seroma and one hematoma was seen. Two small herniations were detected at the suture line in the allo-group. No surgical site infections were observed. Histologically, graft neovascularization was observed in all animals. Infiltration of T-lymphocytes was seen at the graft interface in both groups, but more in the allo-group (p < 0.0001). Deposition of collagen was not different between groups. Macrophages were present in both groups around sutures and in the center more abundantly in the allo-group (p = 0.0001). Graft stiffness and strength were similar for both groups. With this model, we showed that allogeneic transplantation without immunosuppression results in favorable short-term inflammatory and mechanical outcomes. Long-term experiments are needed to further evaluate the effect on graft integration and hernia development.
复杂的腹壁修复仍然是一项重大的手术挑战。在移植患者中,无血管直肌筋膜(NVRF)被成功用于弥补缺损。为了将这一方法推广到非移植患者中,我们建立了一个无免疫抑制的无血管直肌筋膜移植兔模型,对同种异体移植进行了比较。对短期结果(4 周)进行了宏观评估(生长、血清肿/血肿、疝和感染)、移植物界面和中心的组织学评估(炎症、新生血管和胶原沉积)以及机械测试。在两组患者中,都观察到了类似的新生血管再造阵列的宏观生长情况。在同步组中,发现了一个血清肿和一个血肿。异体组在缝合线处发现两个小的疝气。未观察到手术部位感染。从组织学角度看,所有动物均观察到移植物新生血管。两组动物的移植物界面都出现了 T 淋巴细胞浸润,但异体组的 T 淋巴细胞浸润更多(p<0.05)。
{"title":"Allogeneic abdominal non-vascularized rectus fascia transplantation without immunosuppression equals syngeneic transplantation in a rabbit model at short-term follow-up","authors":"Nele Van De Winkel ,&nbsp;Marina Gabriela M.C. Mori da Cunha ,&nbsp;Antoine Dubois ,&nbsp;Ewout Muylle ,&nbsp;Lisanne Terrie ,&nbsp;Ina Hennion ,&nbsp;Gert De Hertogh ,&nbsp;Heleen Fehervary ,&nbsp;Lieven Thorrez ,&nbsp;Marc Miserez ,&nbsp;Jacques Pirenne ,&nbsp;André D’Hoore ,&nbsp;Laurens J. Ceulemans","doi":"10.1016/j.trim.2024.102138","DOIUrl":"10.1016/j.trim.2024.102138","url":null,"abstract":"<div><div>Complex abdominal wall repair remains a major surgical challenge. In transplant patients, non-vascularized rectus fascia (NVRF) is successfully used to bridge the defect. To extrapolate this to non-transplant patients, we developed a rabbit model of NVRF-transplantation without immunosuppression comparing syngeneic versus allogeneic transplants. Short-term outcome (4 weeks) was evaluated macroscopically (ingrowth, seroma/hematoma, herniation, and infection), histologically at the graft interface and center (inflammation, neovascularization, and collagen deposition) and by mechanical testing. In both groups a similar macroscopic ingrowth of the NVRF was observed. In the <em>syn</em>-group, one seroma and one hematoma was seen. Two small herniations were detected at the suture line in the allo-group. No surgical site infections were observed. Histologically, graft neovascularization was observed in all animals. Infiltration of T-lymphocytes was seen at the graft interface in both groups, but more in the allo-group (<em>p</em> &lt; 0.0001). Deposition of collagen was not different between groups. Macrophages were present in both groups around sutures and in the center more abundantly in the allo-group (<em>p</em> = 0.0001). Graft stiffness and strength were similar for both groups. With this model, we showed that allogeneic transplantation without immunosuppression results in favorable short-term inflammatory and mechanical outcomes. Long-term experiments are needed to further evaluate the effect on graft integration and hernia development.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 102138"},"PeriodicalIF":1.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508760","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
Evaluation of new-onset BK viruria in post-renal transplant recipients by quantitative PCR 通过定量 PCR 评估肾移植后受者中新发的 BK 病毒感染。
IF 1.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-10-04 DOI: 10.1016/j.trim.2024.102136
Raza Ullah Asif, Eijaz Ghani, Muhammad Ali Rathore, Saadiya Mushtaq, Faraz Ahmed, Hammad Hussain

Background

The BK polyomavirus infection poses a substantial challenge for organ transplant recipients due to immunosuppression, resulting in BK virus-associated nephropathy (BKVAN) and a considerable risk of graft loss. Screening and prompt decrease of immunosuppression are essential for averting these consequences. We examined the frequency of BK viruria (viral load in urine) among post-renal transplant recipients, along with its association with age, viral load, and the timing of viral reactivation.

Methods

The prospective cohort study was conducted at the Tertiary Care Hospital in Rawalpindi over a 12-month period, from January 1 to December 31, 2023. Urine specimens from 108 renal transplant recipients were collected and analysed for BK viruria every three months during the follow-up assessments. DNA extraction was performed using TANbead extractor, and amplification was carried out with Bio-Rad CFX-96 thermal cycler using Sacace TM amplification kit. Data was analysed using SPSS version 27.

Results

In the cohort of 108 renal transplant recipients, BK viruria was detected in 16.7 % of cases. There was a higher prevalence of BK viruria in females (20 %) than males (16 %). The majority of positive cases were within the 41–60 years age group (61.1 %). Most of the patients (66.6 %) had viral loads below 1 million copies/ml. BK viruria was predominantly detected during the third quarter (between 7 and 9 months) post-transplant. The Chi-square test was applied between age and viral load, showing a significant association (p = 0.01). Similarly, gender and viral load also showed a significant relationship (p = 0.019).

Conclusion

The study showed the frequency of 16.7 % of BK viruria in our small cohort after renal transplantation during the initial 12 months post-transplant. Age of recipients correlated with viral load and time of viral reactivation: middle-aged recipients had higher viral loads. BK viruria increased progressively over the initial nine months, with peak incidence in the third quarter post-transplant.
背景:由于免疫抑制,BK 多瘤病毒感染给器官移植受者带来了巨大挑战,导致 BK 病毒相关性肾病(BKVAN)和相当大的移植物丢失风险。筛查和及时减少免疫抑制对避免这些后果至关重要。我们研究了肾移植术后受者出现 BK 病毒尿(尿液中病毒载量)的频率及其与年龄、病毒载量和病毒再激活时间的关系:这项前瞻性队列研究于 2023 年 1 月 1 日至 12 月 31 日在拉瓦尔品第三级医院进行,为期 12 个月。在随访评估期间,每三个月收集 108 名肾移植受者的尿液标本并分析 BK 病毒。使用 TANbead 提取器提取 DNA,并使用 Bio-Rad CFX-96 热循环仪和 Sacace TM 扩增试剂盒进行扩增。数据使用 SPSS 27 版进行分析:结果:在 108 例肾移植受者中,16.7% 的病例检测出 BK 病毒。女性 BK 病毒感染率(20%)高于男性(16%)。大多数阳性病例年龄在 41-60 岁之间(61.1%)。大多数患者(66.6%)的病毒载量低于 100 万拷贝/毫升。BK 病毒主要在移植后第三季度(7 至 9 个月)检测到。年龄与病毒载量之间进行了卡方检验,结果显示两者之间存在显著关联(p = 0.01)。同样,性别与病毒载量也有显著关系(P = 0.019):研究表明,在我们的小规模队列中,肾移植后最初 12 个月内 BK 病毒感染率为 16.7%。受者年龄与病毒载量和病毒再激活时间相关:中年受者的病毒载量较高。在最初的九个月中,BK 病毒感染率逐渐增加,在移植后的第三季度达到高峰。
{"title":"Evaluation of new-onset BK viruria in post-renal transplant recipients by quantitative PCR","authors":"Raza Ullah Asif,&nbsp;Eijaz Ghani,&nbsp;Muhammad Ali Rathore,&nbsp;Saadiya Mushtaq,&nbsp;Faraz Ahmed,&nbsp;Hammad Hussain","doi":"10.1016/j.trim.2024.102136","DOIUrl":"10.1016/j.trim.2024.102136","url":null,"abstract":"<div><h3>Background</h3><div>The BK polyomavirus infection poses a substantial challenge for organ transplant recipients due to immunosuppression, resulting in BK virus-associated nephropathy (BKVAN) and a considerable risk of graft loss. Screening and prompt decrease of immunosuppression are essential for averting these consequences. We examined the frequency of BK viruria (viral load in urine) among post-renal transplant recipients, along with its association with age, viral load, and the timing of viral reactivation.</div></div><div><h3>Methods</h3><div>The prospective cohort study was conducted at the Tertiary Care Hospital in Rawalpindi over a 12-month period, from January 1 to December 31, 2023. Urine specimens from 108 renal transplant recipients were collected and analysed for BK viruria every three months during the follow-up assessments. DNA extraction was performed using TANbead extractor, and amplification was carried out with Bio-Rad CFX-96 thermal cycler using Sacace TM amplification kit. Data was analysed using SPSS version 27.</div></div><div><h3>Results</h3><div>In the cohort of 108 renal transplant recipients, BK viruria was detected in 16.7 % of cases. There was a higher prevalence of BK viruria in females (20 %) than males (16 %). The majority of positive cases were within the 41–60 years age group (61.1 %). Most of the patients (66.6 %) had viral loads below 1 million copies/ml. BK viruria was predominantly detected during the third quarter (between 7 and 9 months) post-transplant. The Chi-square test was applied between age and viral load, showing a significant association (<em>p</em> = 0.01). Similarly, gender and viral load also showed a significant relationship (<em>p</em> = 0.019).</div></div><div><h3>Conclusion</h3><div>The study showed the frequency of 16.7 % of BK viruria in our small cohort after renal transplantation during the initial 12 months post-transplant. Age of recipients correlated with viral load and time of viral reactivation: middle-aged recipients had higher viral loads. BK viruria increased progressively over the initial nine months, with peak incidence in the third quarter post-transplant.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 102136"},"PeriodicalIF":1.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381726","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
期刊
Transplant immunology
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