Frontiers in Transplantation最新文献

Editorial: Immunosenescence in organ transplantation 社论：器官移植中的免疫衰老

Frontiers in Transplantation Pub Date : 2024-06-14 DOI: 10.3389/frtra.2024.1422358

J. Iske, Hao Zhou

引用次数: 0

Monocyte-derived dendritic cells can be detected in urine of kidney transplant recipients with pathogenic asymptomatic bacteriuria 在患有致病性无症状菌尿的肾移植受者尿液中可检测到单核细胞衍生的树突状细胞

Frontiers in Transplantation Pub Date : 2024-06-12 DOI: 10.3389/frtra.2024.1366104

Vanja Salvadé, Oriol Manuel, D. Golshayan, Carolina Obregon

{"title":"Monocyte-derived dendritic cells can be detected in urine of kidney transplant recipients with pathogenic asymptomatic bacteriuria","authors":"Vanja Salvadé, Oriol Manuel, D. Golshayan, Carolina Obregon","doi":"10.3389/frtra.2024.1366104","DOIUrl":"https://doi.org/10.3389/frtra.2024.1366104","url":null,"abstract":"Urinary tract infections (UTI) are an important clinical problem in kidney transplant recipients (KTR). Asymptomatic bacteriuria (ASB) is frequent in these patients and often resolved by the immune system, but a significant proportion may progress to complicated UTI, which may compromise allograft function and survival. It is essential to determine the involvement of the immune system in the infectious process. Dendritic cells (DCs) are recognised as playing a pivotal role in initiating inflammatory responses capable of priming antigen-specific T cells, a crucial step in determining the fate of local inflammation. Little is known about their role in the control of UTI. In this brief communication, we report an incidental finding in a group of 16 stable KTR in which monocyte-derived dendritic cells (ModDCs), analysed by flow cytometry, were found in urine of patients with ASB and high bacterial counts >107 cfu/ml. Within this group, one patient developed pyelonephritis in the following days. These findings suggest that the immune system, in particular DCs, may be recruited during the course of a UTI and, to our knowledge, present for the first time evidence that inflammatory ModDCs can be detected in urine. Their frequency may reflect the degree of infection. This finding suggests the potential for exploring whether these cells may be useful in distinguishing between pathogenic ASB and those that can be resolved by the immune system.","PeriodicalId":317938,"journal":{"name":"Frontiers in Transplantation","volume":"4 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141350993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Challenges and opportunities for designing clinical trials for antibody mediated rejection 设计抗体介导的排斥反应临床试验的挑战与机遇

Frontiers in Transplantation Pub Date : 2024-06-12 DOI: 10.3389/frtra.2024.1389005

Suryanarayanan Balakrishnan, Mariam P. Alexander, Carrie Schinstock

引用次数: 0

Interactions of TTV with BKV, CMV, EBV, and HHV-6A and their impact on post-transplant graft function in kidney transplant recipients TTV 与 BKV、CMV、EBV 和 HHV-6A 的相互作用及其对肾移植受者移植后移植物功能的影响

Frontiers in Transplantation Pub Date : 2024-06-11 DOI: 10.3389/frtra.2024.1393838

K. Rosiewicz, A. Blazquez-Navarro, Sviatlana Kaliszczyk, Chris Bauer, M. Or-Guil, R. Viebahn, P. Zgoura, Petra Reinke, T. Roch, Christian Hugo, Timm H Westhoff, C. Thieme, U. Stervbo, Nina Babel

{"title":"Interactions of TTV with BKV, CMV, EBV, and HHV-6A and their impact on post-transplant graft function in kidney transplant recipients","authors":"K. Rosiewicz, A. Blazquez-Navarro, Sviatlana Kaliszczyk, Chris Bauer, M. Or-Guil, R. Viebahn, P. Zgoura, Petra Reinke, T. Roch, Christian Hugo, Timm H Westhoff, C. Thieme, U. Stervbo, Nina Babel","doi":"10.3389/frtra.2024.1393838","DOIUrl":"https://doi.org/10.3389/frtra.2024.1393838","url":null,"abstract":"Mono and combined reactivation of latent viruses occurs frequently under immunosuppressive therapy in kidney transplant patients. Recently, monitoring torque teno virus (TTV) reactivation came more into focus as a potential biomarker for immune status. The surrogate characteristics of TTV reactivation on acute rejection, and the combined reactivation with other latent viruses such as cytomegalovirus (CMV), human BK virus (BKV), Epstein–Barr virus (EBV), and human herpes virus-6A (HHV-6A) on allograft function, are unknown so far.Blood samples from 93 kidney transplant recipients obtained during the first post-transplant year were analyzed for TTV/BKV/CMV/EBV/HHV-6A load. Clinical characteristics, including graft function [glomerular filtration rate (GFR)], were collected in parallel.TTV had the highest prevalence and viral loads at 100% and a mean of 5.72 copies/ml (cp/ml) (log10). We found 28.0%, 26.9%, 7.5%, and 51.6% of simultaneous reactivation of TTV with BKV, CMV, EBV, and HHV-6, respectively. These combined reactivations were not associated with a significantly reduced estimated GFR at month 12. Of interest, patients with lower TTV loads <5.0 cp/ml (log10) demonstrated not only a higher incidence of acute rejection, but also an unexpected significantly earlier occurrence and higher incidence of BKV and HHV-6A reactivation. Correlations between TTV loads, other latent viruses, and immunosuppressive medication were only significant from 6 months after transplant.We were able to observe and support previously introduced TTV load thresholds predicting kidney allograft rejection. However, due to a possible delayed relation between immunosuppressive medication and TTV viral load adaptation, the right time points to start using TTV as a biomarker might need to be further clarified by other and better designed studies.","PeriodicalId":317938,"journal":{"name":"Frontiers in Transplantation","volume":"43 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141355031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advancing vascularized composite allotransplantation: essential factors for upper extremity transplant program development 推进血管化复合异体移植：上肢移植项目发展的基本要素

Frontiers in Transplantation Pub Date : 2024-06-11 DOI: 10.3389/frtra.2024.1406626

Martin Kumnig, Caroline Kobler, Alessandra Zaccardelli, G. Brandacher, Simon G. Talbot

{"title":"Advancing vascularized composite allotransplantation: essential factors for upper extremity transplant program development","authors":"Martin Kumnig, Caroline Kobler, Alessandra Zaccardelli, G. Brandacher, Simon G. Talbot","doi":"10.3389/frtra.2024.1406626","DOIUrl":"https://doi.org/10.3389/frtra.2024.1406626","url":null,"abstract":"Vascularized Composite Allotransplantation (VCA) offers a unique option to restore form and function after limb loss or facial trauma that cannot be satisfactorily accomplished through traditional prosthetics or reconstructions. Establishing a successful Upper Extremity Transplantation (UET) program requires strong leadership and a structured surgical team, and extensive interdisciplinary collaboration. We conducted a qualitative study among 12 health care professionals and patients. Informed consent was obtained per protocol, and semi-structured interviews were conducted online and recorded. Participants reported their perceptions of factors that either favored or hindered a successful outcome, including functional status before and after surgery, preparation for transplant, shared decision-making, rehabilitation, and psychosocial support. Thematic analysis revealed that it is essential to establish a team comprising various disciplines well before performing VCA procedures. Defining a common goal and choosing a defined leader is a key factor in procedural success and requires open collaboration beyond what is typical. Primary described categories are interdisciplinary collaboration and skills of the VCA team, building and leading a VCA team, pre-transplant procedures, post-transplant course, and factors to consider when establishing a program. The basic roles of team science play an outsized role in establishing a VCA program. Transplantation medicine involves various overlapping scientific and medical categories requiring health professionals to consciously work together to establish complex vertical and horizontal communication webs between teams to obtain positive outcomes. In addition to medical considerations, patient-specific factors such as transparent communication, therapy plan establishment, plan adherence, and continual follow-up are significant factors to overall success.","PeriodicalId":317938,"journal":{"name":"Frontiers in Transplantation","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141360138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Innate and adaptive effector immune drivers of cytomegalovirus disease in lung transplantation: a double-edged sword 肺移植中巨细胞病毒疾病的先天性和适应性效应免疫驱动因素：一把双刃剑

Frontiers in Transplantation Pub Date : 2024-06-10 DOI: 10.3389/frtra.2024.1388393

Reena Bharti, Daniel R. Calabrese

{"title":"Innate and adaptive effector immune drivers of cytomegalovirus disease in lung transplantation: a double-edged sword","authors":"Reena Bharti, Daniel R. Calabrese","doi":"10.3389/frtra.2024.1388393","DOIUrl":"https://doi.org/10.3389/frtra.2024.1388393","url":null,"abstract":"Up to 90% of the global population has been infected with cytomegalovirus (CMV), a herpesvirus that remains latent for the lifetime of the host and drives immune dysregulation. CMV is a critical risk factor for poor outcomes after solid organ transplant, though lung transplant recipients (LTR) carry the highest risk of CMV infection, and CMV-associated comorbidities compared to recipients of other solid organ transplants. Despite potent antivirals, CMV remains a significant driver of chronic lung allograft dysfunction (CLAD), re-transplantation, and death. Moreover, the extended utilization of CMV antiviral prophylaxis is not without adverse effects, often necessitating treatment discontinuation. Thus, there is a critical need to understand the immune response to CMV after lung transplantation. This review identifies key elements of each arm of the CMV immune response and highlights implications for lung allograft tolerance and injury. Specific attention is paid to cellular subsets of adaptive and innate immune cells that are important in the lung during CMV infection and reactivation. The concept of heterologous immune responses is reviewed in depth, including how they form and how they may drive tissue- and allograft-specific immunity. Other important objectives of this review are to detail the emerging role of NK cells in CMV-related outcomes, in addition to discussing perturbations in CMV immune function stemming from pre-existing lung disease. Finally, this review identifies potential mechanisms whereby CMV-directed treatments may alter the cellular immune response within the allograft.","PeriodicalId":317938,"journal":{"name":"Frontiers in Transplantation","volume":"11 20","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141363148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of removing OPTN region from vascularized composite allograft allocation 从血管化复合异体移植物分配中移除 OPTN 区域的影响

Frontiers in Transplantation Pub Date : 2024-05-16 DOI: 10.3389/frtra.2024.1399357

Sarah E. Booker, Jesse Howell, Thomas G. Dolan, Kelley Poff, Krissy Laurie, W. Cherikh, David K. Klassen, J. Wainright

{"title":"Impact of removing OPTN region from vascularized composite allograft allocation","authors":"Sarah E. Booker, Jesse Howell, Thomas G. Dolan, Kelley Poff, Krissy Laurie, W. Cherikh, David K. Klassen, J. Wainright","doi":"10.3389/frtra.2024.1399357","DOIUrl":"https://doi.org/10.3389/frtra.2024.1399357","url":null,"abstract":"On 6/18/2020, the Organ Procurement and Transplantation Network (OPTN) implemented new policy replacing OPTN region with a 500 nautical mile (NM) circle around the donor hospital for the purpose of vascularized composite allograft (VCA) allocation. We used OPTN data to assess deceased donor VCA transplants in the 3 years pre- (6/19/2017–6/17/2020) vs. post-implementation (6/18/2020–6/17/2023). A total of 19 deceased donor VCA transplants were performed pre-policy (10 uterus, 3 bilateral upper limb, 1 unilateral upper limb, 3 face, 1 abdominal wall and 1 penis), and 11 post-policy (4 uterus, 1 bilateral upper limb, 2 face, 1 trachea, 2 abdominal wall, and 1 bilateral upper limb and face). Median distance from donor hospital to transplant hospital increased from 70 NM (range: 0–524 NM) pre-policy to 119 NM (range: 0–464 NM) post-policy. The majority of transplants in both policy eras were within 500 NM of the donor hospital [89.5% (N = 17/19) vs. 100% (N = 11/11)] and most remained within the same OPTN region as the donor hospital [68.4% (N = 13/19) vs. 90.9% (N = 10/11)]. Although it is difficult to draw strong conclusions about the policy's impact due to the low transplant volume and timing of implementation relative to the COVID-19 pandemic, data in the 3 years post-implementation suggest that 500 NM circles were a reasonable replacement for OPTN region in VCA allocation. The OPTN will continue to review data to monitor the policy's impact and inform future changes to VCA allocation, such as the transition to continuous distribution, a points-based framework expected to replace the current framework.","PeriodicalId":317938,"journal":{"name":"Frontiers in Transplantation","volume":"56 41","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140970103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

invariant Natural Killer T cell therapy as a novel therapeutic approach in hematological malignancies 将不变量杀伤性 T 细胞疗法作为血液恶性肿瘤的一种新型治疗方法

Frontiers in Transplantation Pub Date : 2024-05-06 DOI: 10.3389/frtra.2024.1353803

Chaiyaporn Boonchalermvichian, Hao Yan, Biki Gupta, Anabel Rubin, Jeanette Baker, Robert S. Negrin

{"title":"invariant Natural Killer T cell therapy as a novel therapeutic approach in hematological malignancies","authors":"Chaiyaporn Boonchalermvichian, Hao Yan, Biki Gupta, Anabel Rubin, Jeanette Baker, Robert S. Negrin","doi":"10.3389/frtra.2024.1353803","DOIUrl":"https://doi.org/10.3389/frtra.2024.1353803","url":null,"abstract":"Invariant Natural Killer T cell therapy is an emerging platform of immunotherapy for cancer treatment. This unique cell population is a promising candidate for cell therapy for cancer treatment because of its inherent cytotoxicity against CD1d positive cancers as well as its ability to induce host CD8 T cell cross priming. Substantial evidence supports that iNKT cells can modulate myelomonocytic populations in the tumor microenvironment to ameliorate immune dysregulation to antagonize tumor progression. iNKT cells can also protect from graft-versus-host disease (GVHD) through several mechanisms, including the expansion of regulatory T cells (Treg). Ultimately, iNKT cell-based therapy can retain antitumor activity while providing protection against GVHD simultaneously. Therefore, these biological properties render iNKT cells as a promising “off-the-shelf” therapy for diverse hematological malignancies and possible solid tumors. Further the introduction of a chimeric antigen recetor (CAR) can further target iNKT cells and enhance function. We foresee that improved vector design and other strategies such as combinatorial treatments with small molecules or immune checkpoint inhibitors could improve CAR iNKT in vivo persistence, functionality and leverage anti-tumor activity along with the abatement of iNKT cell dysfunction or exhaustion.","PeriodicalId":317938,"journal":{"name":"Frontiers in Transplantation","volume":"30 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141009134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of a large animal orthotopic intestinal transplantation model with long-term survival for study of immunologic outcomes 开发可长期存活的大型动物矫形肠移植模型，用于研究免疫学结果

Frontiers in Transplantation Pub Date : 2024-05-02 DOI: 10.3389/frtra.2024.1367486

Sarah Merl, Bryan Chen, M. E. Gunes, Hussein Atta, Kryscilla Yang, Dilrukshi K. Ekanayake-Alper, Dominik Hajosi, Fei Huang, Brittany Bhola, Satyajit Patwardhan, Philip Jordache, Greg Nowak, Mercedes Martinez, Tomoaki Kato, Megan Sykes, Kazuhiko Yamada, Joshua Weiner

{"title":"Development of a large animal orthotopic intestinal transplantation model with long-term survival for study of immunologic outcomes","authors":"Sarah Merl, Bryan Chen, M. E. Gunes, Hussein Atta, Kryscilla Yang, Dilrukshi K. Ekanayake-Alper, Dominik Hajosi, Fei Huang, Brittany Bhola, Satyajit Patwardhan, Philip Jordache, Greg Nowak, Mercedes Martinez, Tomoaki Kato, Megan Sykes, Kazuhiko Yamada, Joshua Weiner","doi":"10.3389/frtra.2024.1367486","DOIUrl":"https://doi.org/10.3389/frtra.2024.1367486","url":null,"abstract":"Intestinal transplantation (ITx) is the last remaining therapy for patients with intestinal failure once parenteral nutrition is no longer an option, however its use is limited by immunological complications, including high rates of rejection and morbidity associated with immunosuppression, such as infection and malignancy. We aimed to develop a large animal model of ITx with which to study the immune response to ITx and to design and test tolerance induction regimens.Learning from prior complications, we developed and progressively improved both surgical methods for the donor and recipient as well as postoperative management strategies. Methods of stoma generation, bowel positioning, vessel preparation, and fluid management were optimized. The immunosuppression strategy mirrored our clinical regimen.As a result of our modifications, results improved from survival less than 1 month to consistent long-term survival with good graft function. We review several techniques that were developed to avoid pitfalls that were encountered, which can be used to optimize outcomes in this model.Achieving long-term survival after swine orthotopic ITx permits immunological analysis and pre-clinical trials in a large animal model of ITx.","PeriodicalId":317938,"journal":{"name":"Frontiers in Transplantation","volume":"13 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141018510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nephrons and non-relapse mortality: simplified comorbidity index and acute kidney injury are associated with NRM in adults undergoing allogeneic hematopoietic cell transplant 肾脏和非复发死亡率：简化合并症指数和急性肾损伤与接受异体造血细胞移植的成人非复发死亡率有关

Frontiers in Transplantation Pub Date : 2024-03-18 DOI: 10.3389/frtra.2024.1352413

Clark Raymond Robinson, Alma Habib, N. Klomjit, Qing Cao, S. Holtan

{"title":"Nephrons and non-relapse mortality: simplified comorbidity index and acute kidney injury are associated with NRM in adults undergoing allogeneic hematopoietic cell transplant","authors":"Clark Raymond Robinson, Alma Habib, N. Klomjit, Qing Cao, S. Holtan","doi":"10.3389/frtra.2024.1352413","DOIUrl":"https://doi.org/10.3389/frtra.2024.1352413","url":null,"abstract":"The Simplified Comorbidity Index (SCI) is a recently published 5-component, pre-transplant tool to predict non-relapse mortality (NRM) in allogeneic hematopoietic cell transplantation (alloHCT) patients. The SCI captures chronic kidney disease (CKD) using estimated glomerular filtration rate (eGFR) based on the CKD-EPI equation (KDIGO 2021 CKD-EPI), which may be more sensitive to predict risk of NRM than the creatinine cut-off in the 16-component, Hematopoietic Cell Transplant—Comorbidity Index (HCT-CI). We retrospectively assessed the ability of the SCI to risk-stratify patients and the impact of acute kidney injury (AKI) to NRM in adults who underwent alloHCT at the University of Minnesota. We included 373 patients who underwent their first alloHCT between 2015 and 2019. Through multivariate analysis, we found that patients with an SCI of greater than 4 had a higher risk of NRM. Additionally, we noted that AKIs stages 2–3 prior to day +100 was independently associated with a 3-fold greater NRM than patients who did not experience clinically significant AKI.","PeriodicalId":317938,"journal":{"name":"Frontiers in Transplantation","volume":"332 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140232811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0