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.
摘要:
实体器官移植受者进行性多灶性白质脑病(PML)的策略主要集中在减少免疫抑制治疗。然而,这种方法疗效有限,移植物丢失的风险很高。这里,我们报道了1例64岁的男性肾移植受者,他在2022年10月出现了PML,患有高度免疫抑制.尽管标准的免疫抑制治疗减少,病人的病情继续恶化,神经症状恶化和脑脊液中JC病毒DNA水平升高证明了这一点。这促使创新使用BKPyV特异性T细胞(BKPyV-VST)疗法,考虑到BK和JC病毒之间的遗传相似性。输注第三方供体BKPyV-VST导致临床稳定,JCVDNA水平显着降低,以及JC病毒特异性T细胞反应的出现,如在ELISpot测定和TCRβ测序中观察到的。这是首例成功的第三方BKPyV-VST特异性治疗的肾脏受者出现PML,无移植物抗宿主病或移植物功能障碍。