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肾移植受者和捷克普通人群中针对 BKPyV 亚型 I 和 IV 的抗体流行率。

Prevalence of antibodies against BKPyV subtype I and IV in kidney transplant recipients and in the general Czech population.

机构信息

Department of Genetics and Microbiology, Faculty of Science, Charles University, Prague, Czech Republic.

Vidia Ltd, Vestec, Czech Republic.

出版信息

J Med Virol. 2019 May;91(5):856-864. doi: 10.1002/jmv.25388. Epub 2019 Jan 16.

Abstract

Active infection with BK polyomavirus (BKPyV) may cause serious complications in transplantation settings. Recently, the level of BKPyV IgG seroreactivity in graft donors has been shown to predict viremia and BKPyV-associated nephropathy in kidney transplant (KTx) recipients. Pretransplantation testing of the donor and recipient BKPyV serostatus could, therefore, identify patients at high risk. For the development of serological immunoassays, antibody response to the predominant BKPyV subtypes (BKPyV-I and BKPyV-IV) was studied using virus-like particle (VLP)-based enzyme-linked immunosorbent assay (ELISA). VLPs made from the capsid protein, VP1, derived from BKPyV-I and BKPyV-IV subtypes were produced using a baculovirus expression system and used as antigens. The tests were used for IgG antibody determination in 50 KTx recipients and 111 healthy blood donors. While 87% of samples reacted with mixed BKPyV-I and BKPyV-IV antigens, only 49% of samples were reactive in both ELISA tests when using BKPyV-I or BKPyV-IV antigens separately. Twenty-seven percent of healthy blood donors and 26% of KTx recipients were reactive only with BKPyV-I, while 9% and 20% were reactive only with BKPyV-IV, respectively. To determine the specificities of the antigens, selected seropositive samples were retested after preadsorption with soluble BKPyV-I, BKPyV-IV, or JC polyomavirus antigens. The experiments confirmed that recombinant VP1 VLP-based ELISAs predominantly detected BKPyV type-specific antibodies. The results imply that anti-BKPyV antibody ELISA tests should contain a mixture of subtype-specific VLP-based antigens instead of antigen derived from the most prevalent BKPyV-I subtype. The tests can be used for serological surveys of BKPyV infection and improved KTx patient management.

摘要

BK 多瘤病毒(BKPyV)的活动性感染可能导致移植环境中的严重并发症。最近,供体中 BKPyV IgG 血清反应性水平已被证明可预测肾移植(KTx)受者的病毒血症和 BKPyV 相关肾病。因此,供体和受者 BKPyV 血清状态的移植前检测可以识别高危患者。为了开发血清学免疫分析,使用病毒样颗粒(VLP)-基于酶联免疫吸附试验(ELISA)研究了针对主要 BKPyV 亚型(BKPyV-I 和 BKPyV-IV)的抗体反应。使用杆状病毒表达系统产生源自 BKPyV-I 和 BKPyV-IV 亚型的衣壳蛋白 VP1 的 VLP,并用作抗原。这些测试用于 50 名 KTx 受者和 111 名健康献血者的 IgG 抗体测定。虽然 87%的样本与混合 BKPyV-I 和 BKPyV-IV 抗原反应,但当分别使用 BKPyV-I 或 BKPyV-IV 抗原时,只有 49%的样本在两种 ELISA 测试中均有反应。27%的健康献血者和 26%的 KTx 受者仅与 BKPyV-I 反应,而分别有 9%和 20%的人仅与 BKPyV-IV 反应。为了确定抗原的特异性,在用可溶性 BKPyV-I、BKPyV-IV 或 JC 多瘤病毒抗原预吸附后,对选定的血清阳性样本进行了重新测试。实验证实,基于重组 VP1 VLP 的 ELISA 主要检测 BKPyV 型特异性抗体。结果表明,抗 BKPyV 抗体 ELISA 测试应包含混合亚型特异性 VLP 基于抗原,而不是源自最常见的 BKPyV-I 亚型的抗原。这些测试可用于 BKPyV 感染的血清学调查和改善 KTx 患者管理。

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