Immune Risk Profile Flags BK Virus Reactivation After Living Donor Kidney Transplant

A low ratio of CD4 to CD8 T cells before surgery, combined with cytomegalovirus seropositivity, was associated with later BK polyomavirus replication in adults who received kidneys from living donors, according to a prospective single-centre study conducted at Uppsala University Hospital in Sweden. The findings, published in BMC Immunology, suggest that a routinely measurable immunological marker may help identify transplant recipients at heightened risk of viral reactivation, although the researchers caution that substantial overlap between patient groups limits the marker’s usefulness for individual risk prediction.

BK polyomavirus is a common virus that establishes latency in the cells lining the urinary tract after primary infection, which typically occurs in childhood. Seroprevalence rates exceed 90 percent in most adult populations. During kidney transplantation, the virus can be transmitted from the donor organ whether the recipient is seronegative or already carries the virus, and the immunosuppressive drugs required to prevent graft rejection increase the risk of both donor-derived transmission and reactivation of latent virus. When replication becomes detectable in blood, a state known as DNAemia, it affects an estimated 10 to 20 percent of kidney transplant recipients during the first year after transplantation and may progress to BK polyomavirus-associated nephropathy in roughly 1 to 10 percent of cases. The condition is a significant cause of graft impairment and loss.

Currently, the most effective management strategy involves reducing immunosuppression, guided by regular monitoring of BK polyomavirus DNA levels in blood or plasma after transplantation. Because previous studies have indicated lower rates of DNAemia and nephropathy among recipients of living donor organs compared with deceased donor organs, the researchers reasoned that uniform screening may lead to over-monitoring in lower-risk populations. Predicting which patients will develop viral replication before transplantation could help optimize screening and reduce unnecessary testing. The living donor setting, with its clinical and logistical standardization, offered a suitable framework for evaluating such approaches.

The study included all consecutive adult living kidney donors and their recipients who underwent transplantation at Uppsala University Hospital between May 12, 2016, and September 24, 2018. Of 73 living donor recipients in the parent cohort, pre-transplant blood samples for immune cell phenotyping were available from 68 recipients, who formed the study population. All recipients were routinely screened for BK polyomavirus DNA in plasma and urine every three months for up to 18 months after transplantation. Blood samples for immune phenotyping were collected just before transplantation, one to two months after, and six months after surgery, with donors sampled at the time of donation as a control group. Lymphocyte populations were quantified using six-color flow cytometry, with additional eight-color panels used to characterize T and B cell subpopulations in detail.

During follow-up, 21 of the 68 recipients, or 31 percent, developed BK polyomavirus replication detectable in blood and/or urine. Eleven recipients, 16 percent, developed DNAemia, including eight with high-level DNAemia, defined as plasma viral DNA of at least 10,000 copies per milliliter, consistent with presumptive BK polyomavirus nephropathy according to the 2024 International Consensus Guidelines, and three with low-level DNAemia. Ten recipients had viruria only. One recipient, 1.5 percent, developed biopsy-confirmed BK polyomavirus-associated nephropathy. The mean time to first viral DNA detection was 3.9 months, with a range of 1.5 to 6 months. Among the donors, eight, or 12.1 percent, had BK polyomavirus viruria.

The Immune Risk Profile, a concept defined by a CD4/CD8 ratio below 1 in combination with cytomegalovirus seropositivity, is considered an indicator of immunosenescence and has previously shown utility in predicting opportunistic infections after kidney transplantation. In this cohort, 17 recipients, or 25 percent, met the criteria for profile positivity, compared with just one donor. All recipients and donors with a CD4/CD8 ratio below 1 were serologically positive for cytomegalovirus, meaning that within this subgroup the serostatus criterion added no discriminatory value beyond the ratio itself. Nine of the 17 profile-positive recipients, 53 percent, went on to develop BK polyomavirus replication, a significantly higher proportion than among profile-negative recipients, with an odds ratio of 3.66 and a 95 percent confidence interval of 1.08 to 10.79. Notably, the single profile-positive donor also had detectable viral DNA in urine, and the corresponding recipient later developed high-level DNAemia.

Beyond the risk profile, the researchers examined whether absolute lymphocyte counts, T cell subpopulations, or changes in CD4 T cell counts over time predicted viral replication. There was no difference in lymphocyte counts before transplantation between recipients who later developed replication and those who did not, although the pre-transplant CD4/CD8 ratio was significantly lower in those who did, at a p value of 0.03. No differences emerged in T or B cell subpopulation counts before transplantation, and the number of activated T cells was too low for reliable assessment. Previously proposed thresholds for total T cell, CD8 T cell, CD4 T cell, and NK cell counts, measured either at transplantation or one to two months afterward, showed no statistically significant association with subsequent replication in this cohort, with all p values exceeding 0.05.

Contrary to the study’s primary hypothesis, the total number of T cells, as well as CD4 and CD8 T cell counts, increased one to two months after transplantation compared with pre-transplant levels in both recipients who developed replication and those who did not. The CD4/CD8 ratio rose slightly in both groups during the same period. While total T cell and CD8 T cell counts remained elevated at six months, the CD4 T cell count returned to baseline by six months in recipients who did not develop replication. B cell counts rose transiently and then returned to pre-transplant levels, and NK cell counts decreased after the first months in recipients without replication. The researchers attribute the early lymphocyte increase to immune reconstitution and redistribution of lymphocyte subsets after engraftment in the context of ongoing immunosuppression.

The study also explored whether donor immune parameters were associated with replication in the corresponding recipients, finding no differences in lymphocyte counts, T and B cell populations, NK cell counts, or CD4/CD8 ratios between donors whose recipients did and did not develop replication, though the limited sample size means modest donor-related effects cannot be excluded. Recipients overall had lower total lymphocyte, T cell, CD4 T cell, and B cell counts and lower CD4/CD8 ratios before transplantation than donors, while their NK cell counts were higher. These differences may partly reflect pre-transplant immunosuppressive therapy in some recipients, such as those receiving ABO-incompatible organs, as well as underlying disease and previous transplants.

The authors emphasize that the observed differences were modest and that substantial overlap between groups limits the clinical utility of these markers for individualizing BK polyomavirus screening. The study’s limitations include follow-up samples obtained from only about 65 percent of recipients, a relatively small cohort with few replication cases that may have limited statistical power to detect modest baseline differences, restriction to living donor recipients, which may limit generalisability to the larger deceased donor population, and the absence of BK polyomavirus serostatus data and precise immunosuppressive dosing information. The researchers conclude that the Immune Risk Profile showed a possible association with BK polyomavirus replication, whereas other routinely available lymphocyte-based parameters lacked sufficient discriminatory value, and that further studies are needed to determine whether these or other immune biomarkers can improve early identification of kidney transplant recipients at risk.

Subject of Research: Cellular immune markers predicting BK polyomavirus replication after living donor kidney transplantation

Article Title: Cellular immune response during BK polyomavirus infection in living donor kidney transplant recipients

Article References: Lorant, C., Eriksson, B.-M., Eich, T., Zur-Mühlen, B. V., Westman, G., & Wiberg, A. (2026). Cellular immune response during BK polyomavirus infection in living donor kidney transplant recipients. BMC Immunology, 27(1), Article 92. https://doi.org/10.1186/s12865-026-00912-x

Image Credits: AI Generated

DOI: 10.1186/s12865-026-00912-x

Keywords: BK polyomavirus, kidney transplantation, living donor, CD4/CD8 ratio, Immune Risk Profile, cytomegalovirus, flow cytometry, DNAemia, nephropathy, immunosuppression, T cells, Uppsala