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Association of post-transplantation anellovirus viral load with kidney transplant rejection in children

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Abstract

Background

Post-transplantation immunosuppressive therapy reduces the risk of graft rejection but raises the risk of infection and malignancy. A biomarker of the level of immunosuppression can be helpful in monitoring immunosuppressive therapy. Inverse correlation between Torque teno virus (TTV) from the Anelloviridae (AV) family load and immune competence was described in previous studies. The aim of this study was to analyze the association between AV family viruses’ kinetics and the risk for graft rejection in the first year after kidney transplantation in children.

Methods

The titers of three genera (TTV, TTMDV, and TTMV) from the AV family were monitored by real-time PCR in consecutive samples from children before and after kidney transplantation.

Results

Twenty-one children who underwent kidney transplantation were enrolled. Five out of 21 patients experienced acute graft rejection within a year from transplantation. We found that in patients who experienced graft rejection, the median titers of TTV and total AV titers at 5–6 months post-transplantation were lower than in those who did not. Using a threshold determined by ROC analysis, significant differences in TTV and total AV load were found between patients who had or did not have graft rejection (p = 0.002 and 0.004, respectively). No association was found between the dominance of any AV genus titer and the likelihood of rejection.

Conclusion

This pilot study suggests that children after kidney transplantation with low TTV and total AV titers 5–6 months post-transplantation are at increased risk for graft rejection within a year after transplantation.

Graphical abstract

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

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Funding

This study was funded by internal hospital grants.

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Authors and Affiliations

  1. Research Laboratory of Infectious Diseases, Shaare Zedek Medical Center, affiliated to the Hadassah - Hebrew University Medical School, 12 Beit Shmuel Street, 91031, Jerusalem, Israel

    Yifat Eldar-Yedidia, Miriam Hillel & Yechiel Schlesinger

  2. Pediatric Nephrology Institute, Shaare Zedek Medical Center, affiliated to the Hadassah - Hebrew University Medical School Jerusalem, Jerusalem, Israel

    Efrat Ben-Shalom, Ruth Belostotsky & Yaacov Frishberg

  3. Department of Pediatrics, Shaare Zedek Medical Center, Jerusalem, Israel

    Efrat Ben-Shalom, Orli Megged, Yaacov Frishberg & Yechiel Schlesinger

  4. Mashav Applied Research, Jerusalem, Israel

    Yossi Freier-Dror

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  1. Yifat Eldar-Yedidia
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Contributions

YEY and MH performed viral load assays and analysis of the laboratory results. YS and YEY designed and oversaw the project, analyzed the data, and wrote the manuscript. EBS, YF, and RB contributed the patients’ samples, the clinical data and provided intellectual input and interpreted the data. OM and YFD performed biostatistical analyses. All authors revised and approved the manuscript.

Corresponding author

Correspondence to Yifat Eldar-Yedidia.

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Ethics approval

This study was approved by the Helsinki committee of the Shaare-Zedek Medical Center, Jerusalem. Oral consents were obtained from the parents of all participants and were documented in the patients' records. The study was performed according to the Good Clinical Practice (GCP) guidelines.

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The authors declare no competing interests.

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Yifat Eldar-Yedidia and Efrat Ben-Shalom contributed equally to this work

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Eldar-Yedidia, Y., Ben-Shalom, E., Hillel, M. et al. Association of post-transplantation anellovirus viral load with kidney transplant rejection in children. Pediatr Nephrol 37, 1905–1914 (2022). https://doi.org/10.1007/s00467-021-05336-w

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  • DOI: https://doi.org/10.1007/s00467-021-05336-w

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