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Marginal zone B cells are required for optimal humoral responses to allograft 边缘区 B 细胞是对同种异体移植物产生最佳体液反应的必要条件。
IF 8.9 2区 医学 Q1 SURGERY
American Journal of Transplantation
Pub Date : 2025-01-01 DOI: 10.1016/j.ajt.2024.09.004
Victoria Gorbacheva, Ran Fan, Brian Gaudette, William M. Baldwin III, Robert L. Fairchild, Anna Valujskikh
Antibody-mediated rejection (AMR) is among the leading causes of graft failure in solid organ transplantation. However, AMR treatment options are limited by an incomplete understanding of the mechanisms underlying de novo donor-specific antibody (DSA) generation. The development of pathogenic isotype-switched DSA in response to transplanted allografts is typically attributed to follicular B cells undergoing germinal center reaction whereas the contribution of other B cell subsets has not been previously addressed. The current study investigated the role of recipient marginal zone B cells (MZ B cells) in DSA responses using mouse models of heart and renal allotransplantation. MZ B cells rapidly differentiate into antibody-secreting cells in response to allotransplantation. Despite the selective depletion of follicular B cells in heart allograft recipients, MZ B cells are sufficient for T-dependent IgM and early IgG DSA production. Furthermore, the presence of intact MZ B cell subset is required to support the generation of pathogenic isotype-switched DSA in renal allograft recipients containing donor-reactive memory helper T cells. These findings are the first demonstration of the role of MZ B cells in humoral alloimmune responses following solid organ transplantation and identify MZ B cells as a potential therapeutic target for minimizing de novo DSA production and AMR in transplant recipients.
抗体介导的排斥反应（AMR）是导致实体器官移植失败的主要原因之一。然而，由于对新供体特异性抗体（DSA）产生的机制了解不全面，AMR 治疗方案受到限制。针对异体移植物的致病性同种型转换 DSA 的产生通常归因于发生生殖中心反应的滤泡 B 细胞，而其他 B 细胞亚群的作用以前尚未涉及。本研究利用小鼠心脏和肾脏异体移植模型研究了受体边缘区（MZ）B细胞在DSA反应中的作用。MZ B细胞在异体移植后迅速分化为分泌抗体的细胞。尽管在心脏同种异体移植受体中选择性地消耗了 FO B 细胞，但 MZ B 细胞仍足以产生 T 依赖性 IgM 和早期 IgG DSA。此外，在含有供体反应性记忆辅助 T 细胞的肾脏异体移植受者中，完整的 MZ B 细胞亚群是支持产生致病性同型转换 DSA 的必要条件。这些发现首次证明了 MZ B 细胞在实体器官移植后体液同种免疫反应中的作用，并确定了 MZ B 细胞作为潜在的治疗靶点，可最大限度地减少移植受者体内 DSA 的新生和 AMR 的产生。
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引用次数: 0
Benefits of liver transplant in critically ill patients with acute-on-chronic liver failure: Implementation of an urgent living-donor program 急慢性肝功能衰竭重症患者接受肝脏移植的益处：实施紧急活体供体计划。
IF 8.9 2区 医学 Q1 SURGERY
American Journal of Transplantation
Pub Date : 2025-01-01 DOI: 10.1016/j.ajt.2024.08.008
Hye-Mee Kwon , Jae Hwan Kim , Sung-Hoon Kim , In-Gu Jun , Jun-Gol Song , Deok-Bog Moon , Gyu-Sam Hwang
We evaluated the liver transplantation (LT) criteria in acute-on-chronic liver failure (ACLF), incorporating an urgent living-donor LT (LDLT) program. Critically ill patients with a Chronic Liver Failure Consortium (CLIF-C) ACLF score (CLIF-C_ACLF_score) ≥65, previously considered unsuitable for LT, were included to explore the excess mortality threshold of the CLIF-C_ACLF_score (CLIF-C_ACLF_score_threshold). We followed 854 consecutive patients with ACLF (276 ACLF grade 2 and 215 ACLF grade 3) over 10 years among 4432 LT recipients between 2008 and 2019. For advanced ACLF patients without immediate deceased-donor (DD) allocation, an urgent LDLT program was expedited. The CLIF-C_ACLF_score_threshold was determined by the metrics of transplant survival benefit: >60% 1-year and >50% 5-year survival rate. In predicting post-LT mortality, the CLIF-C_ACLF_score outperformed the (model for end-stage liver disease-sodium) MELD-Na and (model for end-stage liver disease) MELD-3.0 scores but was comparable to the Sundaram ACLF-LT-mortality score. A CLIF-C_ACLF_score ≥65 (n = 54) demonstrated posttransplant survival benefits, with 1-year and 5-year survival rates of 66.7% and 50.4% (P < .001), respectively. Novel CLIF-C_ACLF_score_threshold for 1-year and 5-year mortalities was 70 and 69, respectively. A CLIF-C_ACLF_score–based nomogram for predicting survival probabilities, integrating cardiovascular disease, diabetes, and donor type (LDLT vs DDLT), was generated. This study suggests reconsidering the criteria for unsuitable LT with a CLIF-C_ACLF_score ≥65. Implementing a timely salvage LT strategy, and incorporating urgent LDLT, can enhance survival rates.
我们评估了急性慢性肝衰竭（ACLF）的肝移植（LT）标准，并纳入了紧急活体肝移植（LDLT）计划。慢性肝衰竭联盟-ACLF评分（CLIF-C_ACLF_score）≥65分的重症患者以前被认为不适合接受LT，我们将他们纳入其中，以探讨CLIF-C_ACLF_score的死亡率阈值（CLIF-C_ACLF_score_threshold）。我们对2008年至2019年期间4432名LT接受者中的854名连续ACLF患者（276名ACLF-2和215名ACLF-3）进行了为期10年的随访。对于没有立即进行死亡供体（DD）分配的晚期 ACLF 患者，我们加快了紧急 LDLT 计划的实施。CLIF-C_ACLF_score_threshold 是根据移植生存获益指标确定的：1 年存活率 >60%，5 年存活率 >50%。在预测 LT 后死亡率方面，CLIF-C_ACLF_评分优于 MELD-Na 和 MELD-3.0 评分，但与 Sundaram ACLF-LT 死亡率（SALT-M）评分相当。CLIF-C_ACLF_score≥65 (n=54)显示了移植后生存的优势，1年和5年生存率分别为66.7%和50.4%（P＜0.05）。
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引用次数: 0
Prolonged Time from Cross Clamp until Normothermic Machine Perfusion Start is Associated with Increased Risk of Early allograft Dysfunction Following DCD Liver Transplant
IF 8.9 2区 医学 Q1 SURGERY
American Journal of Transplantation
Pub Date : 2025-01-01 DOI: 10.1016/j.ajt.2024.12.022
Charles Lee , Amit Mathur , Julie Heimbach , C. Burcin Taner , Bashar Aqel , Shennen Mao , Kristopher Croome
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引用次数: 0
Perceptions of Alcohol Use Disorder Support Among Liver Transplant Recipients, A Survey of Strategies and Challenges
IF 8.9 2区 医学 Q1 SURGERY
American Journal of Transplantation
Pub Date : 2025-01-01 DOI: 10.1016/j.ajt.2024.12.101
Maria Cote, Natalia Rodriguez-Payan, Leigh Anne Dageforde
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引用次数: 0
Renal Transplant Graft Survival After Normothermic Regional Perfusion Is Comparable To Other Standard Procurement Methods
IF 8.9 2区 医学 Q1 SURGERY
American Journal of Transplantation
Pub Date : 2025-01-01 DOI: 10.1016/j.ajt.2024.12.062
Caroline Godfrey , Kathryn Kraft , Scott Rega , Irene Feurer , Wali Johnson , David Shaffer , Rachel Forbes , Laura Hickman
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引用次数: 0
Unexpected challenges after kidney transplant: The patient experience
IF 8.9 2区 医学 Q1 SURGERY
American Journal of Transplantation
Pub Date : 2025-01-01 DOI: 10.1016/j.ajt.2024.12.063
Natalie Gorham , Raphael Meier , Amit Pal Singh , Grace Chiodo , Sarah Bova , Silke Niederhaus
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引用次数: 0
The Renin-Angiotensin-Aldosterone Axis in a Living Human Recipient with Porcine Xenothymokidney and Intact Native Kidneys
IF 8.9 2区 医学 Q1 SURGERY
American Journal of Transplantation
Pub Date : 2025-01-01 DOI: 10.1016/j.ajt.2024.12.060
Tal Eitan , Imad Aljabban , Jacqueline Kim , Ian Jaffe , Karen Khalil , Summer Viscusi , Elaina Weldon , David Ayares , Bernard Kadosh , Randal Goldberg , Tajinderpal Saraon , Alex Reyentovich , Deane Smith , Sapna Mehta , Jeffrey Stern , Adam Griesemer , Robert Montgomery , Nader Moazami , Edward Skolnik , Aprajita Mattoo , Vasishta Tatapudi
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引用次数: 0
Factors Associated with Liver Cradle Compression Effect Following Normothermic Machine Perfusion
IF 8.9 2区 医学 Q1 SURGERY
American Journal of Transplantation
Pub Date : 2025-01-01 DOI: 10.1016/j.ajt.2024.12.048
Vijay Subramanian , Grant Weiderman , Venkata Yeddula , Emma Kotelnicki , Milana Mudra , Kaidyn White , Kiran Dhanireddy
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引用次数: 0
Increasing Access to DCD Liver Transplant via Perfusion Technology: Time is On Our Side
IF 8.9 2区 医学 Q1 SURGERY
American Journal of Transplantation
Pub Date : 2025-01-01 DOI: 10.1016/j.ajt.2024.12.106
Anna Ha, Carlos Goncalves, David Reynolds, Cassidy Yoshida, David Chen, Tiffany Maksimuk, Trevor Nydam, Jesse Schold, Bruce Kaplan, Elizabeth Pomfret, James Pomposelli, Yanik Bababekov
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引用次数: 0
Assessing clinical benefits of live-attenuated vaccination in post-liver transplant patients: Analysis of breakthrough infections and natural boosters 评估肝移植后患者接种减毒活疫苗的临床益处：对突破性感染和自然增效的分析。
IF 8.9 2区 医学 Q1 SURGERY
American Journal of Transplantation
Pub Date : 2025-01-01 DOI: 10.1016/j.ajt.2024.07.005
Masayoshi Shinjoh , Munehiro Furuichi , Yohei Yamada , Takuma Ohnishi , Mizuki Yaginuma , Ken Hoshino , Tetsuo Nakayama
Recently, live-attenuated measles, rubella, varicella, and mumps vaccines have been administered to carefully selected post-liver transplant patients. Although attention has been focused on post-vaccination antibody titers and adverse events, the real-life clinical benefits remain unclear. A comprehensive analysis of breakthrough infections and natural boosters (asymptomatic cases with significant elevation in virus antibody titers) following immunization post-liver transplantation was conducted from 2002-2023, exploring the timing, frequency, correlation with domestic outbreaks, and degree of antibody elevation. During the median 10-year observation period among 68 post-liver transplant patients, breakthrough infections occurred only in chickenpox, with 7 mild cases (1 episode/64 person-years). A total of 59 natural booster episodes (1, 5, 20, and 33 for measles, rubella, chickenpox, and mumps, respectively) were observed, with incidence rates of 1 per 569, 110, 22, and 17 person-years, respectively. The timing of natural boosters closely correlated with domestic outbreaks (P < .05 in chickenpox and mumps), influenced by local vaccine coverage. The degree of antibody elevation was significantly higher in individuals with breakthrough infections than in those with natural boosters (P < .05). These findings suggest that immunization with live-attenuated vaccines for post-liver transplant patients has demonstrated clinical benefits. Furthermore, mass vaccination has a positive impact on post-transplant patient outcomes.
最近，经过精心挑选的肝移植术后患者接种了麻疹、风疹、水痘和腮腺炎减毒活疫苗。虽然疫苗接种后的抗体滴度和不良反应一直备受关注，但其实际临床益处仍不明确。从 2002 年到 2023 年，我们对肝移植后免疫接种后的突破性感染和自然增殖（病毒抗体滴度显著升高的无症状病例）进行了全面分析，探讨了感染的时间、频率、与国内疫情爆发的相关性以及抗体升高的程度。在 68 名肝移植后患者的中位 10 年观察期内，突破性感染仅发生在水痘方面，其中有 7 例轻微病例（1 次/64 人-年）。共观察到 59 次自然强化（麻疹、风疹、水痘和流行性腮腺炎分别为 1、5、20 和 33 次），发病率分别为每 569 人年 1 次、110 人年 1 次、22 人年 1 次和 17 人年 1 次。自然强化免疫的时间与国内疫情爆发密切相关（p
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