BK virus antibody titers and intensity of infections after renal transplantation
Introduction
BK virus (BKV), a human polyomavirus, causes nephropathy (BKN) and allograft loss in renal transplant recipients. Although it was discovered in 1971,1 understanding of the humoral immune response to BKV is limited.
By age 10, 90% of children have antibodies to BKV.2, 3 After primary infection, BKV remains latent in the uroepithelium, but can reactivate after transplant and cause allograft dysfunction.4
The significance of the donor or the recipient BKV antibody serostatus is unclear. In pediatric kidney transplant recipients, a negative recipient serostatus was a risk factor for BK viruria5, and nephropathy.6 This is less clear in adults.7, 8, 9 In 1984, Gardner10 reported that the antibody titer was initially low, rose greater than 100-fold, and persisted in 6 kidney transplant recipients in whom BK virus was isolated by urine culture, suggesting that the antibody was non-neutralizing. In 2005, Hariharan11 showed that BKV-specific IgG, but not IgM, levels increased in 6 recipients with BKN after reduction in immunosuppression and clearance of viremia. They did not investigate titers from those without active BK infection or those without nephropathy.
We showed that the mean urine BK viral load in 70 kidney transplant recipients increases as the infection progresses from no infection, to transient viruria, sustained viruria, transient viremia, and finally sustained viremia.12 To investigate whether the intensity of infection is associated with the humoral immune response, we evaluated BKV-specific IgG levels, pre-transplant and serially post-transplant in renal transplant recipients with and without BKV infections (controls). Serial plasma samples had been tested by quantitative PCR for BK virus DNA, allowing us to compare the anti-BKV-antibody level with the BKV-viral load and correlate it with the overall severity of infection.
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Subjects and samples
Two hundred renal transplant recipients were enrolled in a trial in which urine and blood samples were obtained weekly for 16 weeks and at months 5, 6, 9, and 12 after transplantation.12 Samples were analyzed by real-time PCR for BKV DNA. Urine, plasma, and whole blood samples and extracted DNA from the samples were stored at −70 °C. Recipients were defined as having active BKV infection if any specimen were positive for BKV by PCR. Clinical characteristics and outcomes, BKV DNA levels, and
Subjects and samples
The demographic characteristics were similar among those without evidence of active BKV infection post-transplant and those with any of the four intensities of BKV infection post-transplant (Table 1).
BKV-specific antibody responses by type of BKV infection
Pre-transplant, the mean antibody titers were lower in those who subsequently developed viremia compared to those who developed viruria without ever developing viremia (DI: 3.36 ± 1.70 vs. 4.64 ± 1.57, p = 0.004). Post-transplant, the mean BK antibody titers increased throughout the first post-transplant
Discussion
The present study is the most extensive comparison to date of serial BKV-specific antibody measurements in renal transplant recipients. A strong point of the study is the comparison of the changes in antibody titers with serial quantitative measurements of BKV DNA in urine and plasma from the same patients. A clear finding is that the BKV antibody response correlated with the intensity of infection as assessed by urine viral load. BKV antibody titers reached higher levels at 1 year after
Conflict of interest
- 1.
D.L. Bohl, G.A. Storch, C. Ryschkewitsch, M. Gaudreault-Keener, and E.O. Major have no conflicts of interest.
- 2.
D.C. Brennan grant support—Astellas, Novartis, Pfizer, Wyeth, and Genzyme. D.C. Brennan is a consultant for Pfizer, Wyeth, and Genzyme and an honorarium recipient from Genzyme.
Acknowledgments
This work was supported in part by NIH 1 K24-02886 (D.C.B.) and NKF 22 3062 38053 (D.L.B.). D.L.B. is a recipient of the 2004 Amgen Renal Fellowship Award.
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2020, Transplantation ProceedingsCitation Excerpt :Additionally, there was a significant correlation between maximum decoy cell count and decoy-cell-free survival (correlation coefficient [r] = -0.7331, P < .0001) in this study group. Some previous studies reported the association between pretransplant BKV serostatus and the incidence of BKV infection [3,18,20,34–36]. KT from seropositive donors has been identified as a risk factor for developing BKV infection.