UR-UPJV4294, Agents Infectieux, Résistance et chimiothérapie (AGIR), Centre Universitaire de Recherche en Santé, Université de Picardie Jules Verne, Amiens, France.
Laboratoire de Virologie, Centre Hospitalier Universitaire, Amiens, France.
J Am Soc Nephrol. 2024 Oct 1;35(10):1425-1433. doi: 10.1681/ASN.0000000000000457. Epub 2024 Jul 9.
Most of the world's adult population is latently infected by the BK polyomavirus. It causes asymptomatic infection in healthy individuals but emerged as a threat to kidney transplant recipients because of virus-associated nephropathy caused by immunosuppressive therapy. In these conditions, when a functional cellular response is impaired by immunosuppression, neutralizing antibodies may play a major role because they can directly prevent infection of target cells, independently of cell-mediated immunity, by binding to the viral particles. Studying the contribution of anti-BK virus neutralizing antibodies in viral control has long been hampered by the lack of convenient in vitro models, but major progress has been made in the past decade. The four BK virus genotypes have been demonstrated to behave as distinct serotypes. A low recipient neutralizing antibody titer against the donor's serotype before kidney transplant has been significantly associated with BK virus replication after transplant. Different mechanisms exploited by the BK virus to evade neutralizing antibodies have been described. Recent studies also support the potential benefit of administering intravenous Igs or monoclonal neutralizing antibodies as a therapeutic strategy, and more interestingly, this could also be used as preventive or preemptive therapy before advanced kidney damage has occurred. Besides, neutralizing antibodies could be induced by vaccination. In this review, we summarize accumulated knowledge on anti-BK virus neutralizing antibodies as well as their clinical importance and therapeutic potential for kidney transplant recipients.
世界上大多数成年人口都潜伏感染 BK 多瘤病毒。它在健康个体中引起无症状感染,但由于免疫抑制治疗引起的病毒相关性肾病,它成为了肾移植受者的威胁。在这些情况下,当细胞免疫受到免疫抑制的损害时,中和抗体可能发挥主要作用,因为它们可以通过与病毒颗粒结合,直接防止靶细胞感染,而不依赖于细胞介导的免疫。由于缺乏方便的体外模型,研究抗 BK 病毒中和抗体在病毒控制中的作用长期以来受到阻碍,但在过去十年中取得了重大进展。已证明四种 BK 病毒基因型表现为不同的血清型。肾移植前受者针对供者血清型的中和抗体滴度低与移植后 BK 病毒复制显著相关。BK 病毒逃避中和抗体的不同机制已被描述。最近的研究还支持静脉注射免疫球蛋白或单克隆中和抗体作为治疗策略的潜在益处,更有趣的是,这也可以在发生严重肾损伤之前作为预防或先发治疗。此外,中和抗体可以通过疫苗接种来诱导。在这篇综述中,我们总结了关于抗 BK 病毒中和抗体的累积知识,以及它们对肾移植受者的临床重要性和治疗潜力。