Pretransplant BKV-IgG serostatus and BKV-specific ELISPOT assays to predict BKV infection after kidney transplantation

Abstract

Introduction: Polyomavirus (BKV) infection can lead to major complications and damage to the graft in kidney transplant recipients (KTRs). We investigated whether pretransplant BK serostatus and BK-specific cell-mediated immunity (CMI) predicts post-transplant BK infection.

Methods: A total of 93 donor-recipient pairs who underwent kidney transplantation (KT) and 44 healthy controls were examined. Assessment of donor and recipient BKV serostatus and BKV-CMI in recipients was performed prior to transplantation using BKV-IgG ELISA and BKV-specific IFN-g ELISPOT assays against five BK viral antigens (LT, St, VP1, VP2, and VP3). BK viremia was diagnosed when blood BKV-DNA of 104 copies/mL or more was detected during follow-up periods.

Results: Anti-BKV IgG antibody was detected in 74 (79.6%) of 93 KTRs and in 68 (73.1%) of 93 KT donors. A greater percentage of KTRs who received allograft from donors with high levels of anti-BKV IgG had posttransplant BK viremia (+) than KTRs from donors with low anti-BKV IgG (25.5% [12/47] vs. 4.3% [2/46], respectively; P = 0.007). Pretransplant total BKV-ELISPOT results were lower in BK viremia (+) patients than in patients without viremia (-) 20.5 [range 9.9-63.6] vs. 72.0 [43.2 - 110.8]; P = 0. 027). The sensitivity and specificity of the total BKV-ELISPOT assay (cut-off ≤ 53 spots/3×105 cells) for prediction of posttransplant BK viremia were 71.4 (95% CI: 41.9-91.6) and 54.4 (42.8-65.7), respectively. The combination of high donor BKV-IgG, low recipient BKV-IgG, and low total BKV-ELISPOT results improved specificity to 91.1%.

Discussion: Our study highlights the importance of pretransplant BKV-IgG serostatus and BKV-specific CMI in predicting posttransplant BKV infection in KTRs. The combination of high donor BKV-IgG, low recipient BKV-IgG, and low total BKV-ELISPOT results predicted BK viremia after KT. Pretransplant identification of patients at highrisk for BK viremia could enable timely interventions and improve clinical outcomes of KTRs.

Keywords: BK polyomavirus; BK viremia; BKV-specific ELISPOT; kidney transplant recipients; pre-transplant BKV-IgG serostatus.

Figure 1

Anti-BKV IgG serostatus (optical density, OD) in 44 healthy controls (HC) and 93 donor (D) and recipients (R) prior kidney transplantation. Donors and recipients were stratified according to the development of posttransplant BK viremia development (BK viremia+) or not (BK viremia-). Donors from BK viremia (+) had higher OD values than donors from BK viremia (-) group (P = 0.01). Red symbols indicate results from five patients with BKV-associated nephropathy.

Figure 2

The incidence of new-onset posttransplant BK viremia was analyzed in 93 kidney transplant recipients (KTRs) according to the pretransplant anti-BKV-IgG serostatus in donors and recipients. Among KTRs, a greater percentage of the high-anti-BKV-IgG donor (D-H) group had posttransplant BK viremia (+) than those in the low-anti-BKV-IgG donor (D-L) group (P = 0.007). Outcomes were also assessed with respect to recipient anti-BKV-IgG serostatus (high anti-BKV-IgG, R-H; low anti-BKV-IgG, R-L). When examining donor/recipient pairs, the incidence of post-transplant BK viremia (+) was 24.0% (6/25) in the D-H/R-H group and 27.3% (6/22) in the D-H/R-L group.

Figure 3

Comparisons of pretransplant BKV-ELISPOT assay results for BKV-specific peptides (LT, ST, VP1, VP2, VP3, and peptide totals) in the healthy control (HC), posttransplant-BK viremia (+), and no-posttransplant BK viremia (-) groups after kidney transplantation (KT). The BKV-associated nephropathy group is represented by a red-filled circle symbol. The long line represents the median and short line represents the 95% CI. The dashed line represents the cut-off value of 53 spot numbers/3 x 10⁵ cells. BK viremia (+) KT recipients had significantly lower ST(B), VP3(E), and TOTAL(F) ELISPOT results than those in the BK viremia (-) group. *P<0.05. CI, confidence interval.

Figure 4

Cumulative incidence of posttransplant BK viremia in kidney transplant recipients stratified by donor pretransplant anti-BKV-IgG serostatus (H, high anti-BKV-IgG levels; L, low anti-BKV-IgG levels) and recipient total BKV-ELISPOT result. Recipients who had low BKV-ELISPOT results and received a kidney from high anti-BKV-IgG donors developed posttransplant BK viremia more frequently than the other patient groups.

Figure 5

A model for predicting risk of BKV infection after transplantation in kidney transplant recipients based on pre-transplant BKV-IgG serostatus and BKV-specific ELISPOT results.