Successful BK virus–specific T cell therapy in a kidney transplant recipient with progressive multifocal leukoencephalopathy

IF 8.9 2区 医学 Q1 SURGERY American Journal of Transplantation Pub Date : 2024-09-01 DOI:10.1016/j.ajt.2024.05.003
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Abstract

The strategy for progressive multifocal leukoencephalopathy (PML) in solid organ transplant recipients primarily focuses on reducing immunosuppressive therapy. However, this approach offers limited efficacy and carries a high risk of graft loss. Here, we present the case of a 64-year-old male kidney transplant recipient with a high degree of immunosuppression who developed PML in October 2022. Despite the standard reduction of immunosuppressive therapy, the patient’s condition continued to deteriorate, as evidenced by worsening neurological symptoms and increasing JC virus (JCV) DNA levels in cerebrospinal fluid. This prompted the innovative use of BKPyV-virus–specific T cell (BKPyV-VST) therapy, given the genetic similarities between BK and JCVs. Infusion of third-party donor BKPyV-VST resulted in clinical stabilization, a significant reduction in JCV-DNA levels, and the emergence of a JCV-specific T cell response, as observed in enzyme-linked immunospot assays and TCRβ sequencing. This represents the first case report of successful third-party BKPyV-VST therapy in a kidney recipient presenting PML, without graft-versus-host disease or graft dysfunction.

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成功治疗一名患有进行性多灶性白质脑病的肾移植受者的 BK 病毒特异性 T 细胞。
实体器官移植受者进行性多灶性白质脑病(PML)的治疗策略主要是减少免疫抑制治疗。然而,这种方法的疗效有限,且存在移植物丢失的高风险。在此,我们介绍了一例 64 岁的男性肾移植受者,他患有高度免疫抑制,于 2022 年 10 月患上了 PML。尽管按照标准减少了免疫抑制治疗,但患者的病情持续恶化,表现为神经系统症状恶化和脑脊液中JC病毒DNA水平升高。鉴于 BK 病毒和 JC 病毒在基因上的相似性,这促使我们创新性地使用了 BKPyV 特异性 T 细胞(BKPyV -VST)疗法。输注第三方供体 BKPyV -VST 后,患者的临床症状趋于稳定,JCV DNA 水平显著降低,并出现了 JC 病毒特异性 T 细胞应答,这一点在 ELISpot 检测和 TCRβ 测序中均有观察到。这是首例成功治疗出现 PML 的肾脏受者的第三方 BKPyV -VST 特异性疗法的病例报告,患者没有出现移植物抗宿主疾病或移植物功能障碍。
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来源期刊
CiteScore
18.70
自引率
4.50%
发文量
346
审稿时长
26 days
期刊介绍: The American Journal of Transplantation is a leading journal in the field of transplantation. It serves as a forum for debate and reassessment, an agent of change, and a major platform for promoting understanding, improving results, and advancing science. Published monthly, it provides an essential resource for researchers and clinicians worldwide. The journal publishes original articles, case reports, invited reviews, letters to the editor, critical reviews, news features, consensus documents, and guidelines over 12 issues a year. It covers all major subject areas in transplantation, including thoracic (heart, lung), abdominal (kidney, liver, pancreas, islets), tissue and stem cell transplantation, organ and tissue donation and preservation, tissue injury, repair, inflammation, and aging, histocompatibility, drugs and pharmacology, graft survival, and prevention of graft dysfunction and failure. It also explores ethical and social issues in the field.
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