Division of Transplantation Pathology, Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Transplantation. 2010 Jun 27;89(12):1462-5. doi: 10.1097/tp.0b013e3181daaaf1.
Polyomavirus BK (BKV) infection can cause nephropathy in the allograft kidney. No well-established drug treatment is available at this time. Human intravenous immunoglobulins (IVIG) have been used as an empiric therapy without proof of effectiveness.
We tested five lots of commercially available IVIG preparations from two different suppliers for polyomavirus neutralizing activity. BKV and mouse polyomavirus were used to infect human and murine host cells, respectively, with or without prior treatment with IVIG. Neutralization activity was measured by quantitation of viral DNA after 7 days in culture.
Coincubation of BKV but not mouse polyomavirus with clinically relevant concentrations of IVIG derived from healthy and hepatitis B vaccinated subjects caused more than 90% inhibition of viral DNA yield after 7 days in culture. Consistent with a direct neutralizing mechanism, this effect was significantly diminished if viral infection was performed in immunoglobulin pretreated cells or if immunoglobulin treatment was delayed 2 hr after addition of infectious virus.
Human IVIG preparations contain BKV neutralizing antibodies. Data on neutralizing capacity of these antibodies are presented to aid dose exploration in clinical trials seeking to validate the use of IVIG in patients with BKV infection.
多瘤病毒 BK(BKV)感染可导致移植肾肾病。目前尚无有效的标准药物治疗方法。人静脉注射免疫球蛋白(IVIG)已被用作经验性治疗方法,但没有有效性的证据。
我们测试了来自两个不同供应商的五种市售 IVIG 制剂对多瘤病毒中和活性。BKV 和小鼠多瘤病毒分别用于感染人源和鼠源宿主细胞,在感染前或感染后用 IVIG 进行处理。培养 7 天后,通过定量检测病毒 DNA 来测量中和活性。
BKV 与临床相关浓度的 IVIG 共同孵育,但小鼠多瘤病毒与 IVIG 共同孵育不会导致培养 7 天后病毒 DNA 产量超过 90%的抑制。与直接中和机制一致,如果在免疫球蛋白预处理的细胞中进行病毒感染,或者如果在添加感染性病毒后 2 小时延迟免疫球蛋白处理,则该效果显著降低。
人 IVIG 制剂含有 BKV 中和抗体。提供这些抗体的中和能力数据有助于在临床试验中探索 IVIG 在 BKV 感染患者中的使用剂量。