Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands.
J Clin Virol. 2019 Jan;110:22-28. doi: 10.1016/j.jcv.2018.11.009. Epub 2018 Dec 1.
The BK polyomavirus (BKPyV) is subdivided into four genotypes. The consequences of each genotype and of donor-recipient genotype (mis)match for BKPyV-associated nephropathy (BKPyVAN) in kidney transplant recipients (KTRs) are unknown.
To develop and evaluate a genotype-specific IgG antibody-based BKPyV serotyping assay, in order to classify kidney transplant donors and recipients accordingly.
VP1 antigens of six BKPyV variants (Ib1, Ib2, Ic, II, III and IV) were expressed as recombinant glutathione-s-transferase-fusion proteins and coupled to fluorescent Luminex beads. Sera from 87 healthy blood donors and 39 KTRs were used to analyze seroreactivity and serospecificity against the different BKPyV genotypes. Six sera with marked BKPyV serotype profiles were analyzed further for genotype-specific BKPyV pseudovirus neutralizing capacity.
Seroreactivity was observed against all genotypes, with seropositivity rates above 77% comparable for KTRs and blood donors. Strong cross-reactivity (r > 0.8) was observed among genotype I subtypes, and among genotypes II, III and IV. Seroresponses against genotypes I and IV seemed genuine, while those against II and III could be out(cross)competed. GMT (Luminex) and IC (neutralization assay) values showed good agreement in determining the genotype with the strongest seroresponse within an individual.
Despite some degree of cross-reactivity, this serotyping assay seems a useful tool to identify the main infecting BKPyV genotype within a given individual. This information, which cannot be obtained otherwise from nonviremic/nonviruric individuals, could provide valuable information regarding the prevalent BKPyV genotype in kidney donors and recipients and warrants further study.
BK 多瘤病毒(BKPyV)分为四个基因型。每个基因型以及供体-受者基因型(错配)对肾移植受者(KTR)BKPyV 相关肾病(BKPyVAN)的影响尚不清楚。
开发和评估一种基于 IgG 抗体的 BKPyV 基因型特异性血清分型检测方法,以便对肾移植供者和受者进行相应分类。
将六个 BKPyV 变体(Ib1、Ib2、Ic、II、III 和 IV)的 VP1 抗原表达为重组谷胱甘肽 S-转移酶融合蛋白,并与荧光 Luminex 珠偶联。使用 87 名健康献血者和 39 名 KTR 的血清来分析针对不同 BKPyV 基因型的血清反应性和血清特异性。进一步分析了 6 份具有明显 BKPyV 血清型特征的血清,以评估其针对基因型特异性 BKPyV 假病毒的中和能力。
观察到针对所有基因型的血清反应性,KTR 和献血者的血清阳性率均高于 77%。基因型 I 亚型之间以及基因型 II、III 和 IV 之间观察到强烈的交叉反应(r > 0.8)。针对基因型 I 和 IV 的血清反应似乎是真实的,而针对 II 和 III 的血清反应可能是交叉反应。在确定个体内最强血清反应的基因型时,Luminex(GMT)和中和测定(IC)值显示出良好的一致性。
尽管存在一定程度的交叉反应,但该血清分型检测方法似乎是一种有用的工具,可以识别特定个体内的主要感染 BKPyV 基因型。从非病毒血症/非病毒尿症个体中无法获得的这种信息,可以提供有关肾供体和受者中流行的 BKPyV 基因型的有价值信息,值得进一步研究。