Hillenbrand Caroline A, Akbari Bani Dorssa, Follonier Océane, Kaur Amandeep, Weissbach Fabian H, Wernli Marion, Wilhelm Maud, Leuzinger Karoline, Binet Isabelle, Bochud Pierre-Yves, Golshayan Dela, Hirzel Cédric, Manuel Oriol, Mueller Nicolas J, Schaub Stefan, Schachtner Thomas, Van Delden Christian, Hirsch Hans H
Transplantation & Clinical Virology, Department of Biomedicine, Medical Faculty, University of Basel, Basel, Switzerland.
Transplantation & Clinical Virology, Department of Biomedicine, Medical Faculty, University of Basel, Basel, Switzerland; Biozentrum, University of Basel, Basel, Switzerland; SIB Swiss Institute of Bioinformatics, Basel, Switzerland.
Am J Transplant. 2025 May;25(5):985-1001. doi: 10.1016/j.ajt.2024.11.019. Epub 2024 Nov 22.
BK polyomavirus (BKPyV) causes premature renal failure in 10% to 30% of kidney transplant recipients (KTRs). Current guidelines recommend screening for new-onset BKPyV-DNAemia/nephropathy and reducing immunosuppression to regain BKPyV-specific immune control. Because BKPyV encompasses 4 major genotype (gt)-encoded serotypes (st1,-2,-3,-4), st-specific antibodies may inform the risk and course of BKPyV-DNAemia/nephropathy. Using BKPyV st-virus-like particle (VLP) enzyme-linked immunosorbent assay, we analyzed plasma from 399 blood donors (BDs) and 428 KTRs (134 KTR-cases with BKPyV-DNAemia, 294 KTR-controls). BDs were anti-BKPyV-VLP immunoglobulin G-seropositive in 85% compared to 93% of KTRs at the timepoint at transplantation (T0) (P < .001). Anti-st1 was predominant in both groups followed by anti-st4, anti-st2, and anti-st3. Antibody levels and quadruple sero-reactivity at T0 were higher in KTR-controls than in KTR-cases (P = .026) or in BDs (P < .001). In KTR-cases, anti-st increased posttransplant (P < .0001) and independently of ongoing or cleared BKPyV-DNAemia. However, anti-st levels were significantly higher at T0 in KTR-cases able to clear at timepoint 6-month posttransplant or timepoint 12-month posttransplant. In 34 KTR-cases with deep genome sequencing, BKPyV-gtI was predominant, and anti-st1 and st1-neutralizing antibodies were significantly lower at T0 than in KTR-controls. Thus, BKPyV st-specific antibody levels at transplantation might reflect gt/st-BKPyV-specific immunity clearing or preventing BKPyV-DNAemia in KTR-cases or KTR-controls, respectively. Accordingly, active or passive immunization may be most efficient pretransplant or early posttransplant.
BK多瘤病毒（BKPyV）可导致10%至30%的肾移植受者（KTR）过早出现肾衰竭。当前指南建议对新发BKPyV病毒血症/肾病进行筛查，并减少免疫抑制以重新获得针对BKPyV的免疫控制。由于BKPyV包含4种主要基因型（gt）编码的血清型（st1、-2、-3、-4），血清型特异性抗体可能有助于了解BKPyV病毒血症/肾病的风险和病程。我们使用BKPyV血清型病毒样颗粒（VLP）酶联免疫吸附测定法，分析了399名献血者（BD）和428名KTR（134例BKPyV病毒血症的KTR病例，294例KTR对照）的血浆。在移植时间点（T0），85%的BD抗BKPyV-VLP免疫球蛋白G呈血清阳性，而KTR的这一比例为93%（P <.001）。两组中抗st1均占主导，其次是抗st4、抗st2和抗st3。KTR对照在T0时的抗体水平和四重血清反应性高于KTR病例（P =.026）或BD（P <.001）。在KTR病例中，移植后抗血清型增加（P <.0001），且与持续或已清除的BKPyV病毒血症无关。然而，在移植后6个月或12个月时间点能够清除BKPyV的KTR病例中，T0时的抗血清型水平显著更高。在34例进行深度基因组测序的KTR病例中，BKPyV-gtI占主导，T0时抗st1和st1中和抗体显著低于KTR对照。因此，移植时的BKPyV血清型特异性抗体水平可能分别反映了gt/st-BKPyV特异性免疫在KTR病例或KTR对照中清除或预防BKPyV病毒血症的情况。相应地，主动或被动免疫可能在移植前或移植后早期最为有效。
