Long-lasting chronic high load carriage of Epstein-Barr virus is more common in young pediatric renal transplant recipients

Susanne Westphal Ladfors,Vanda Friman,Magnus Lindh,Per Brandström,Susanne Woxenius,Marianne Jertborn,Sverker Hansson,Jenny K Lindahl,Rune Andersson

doi:10.1007/s00467-019-04401-9

Susanne Westphal Ladfors, Vanda Friman + Show 7 more

Open Access

https://doi.org/10.1007/s00467-019-04401-9

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Abstract

BackgroundEpstein-Barr virus (EBV) infections can induce post-transplant lymphoproliferative disorder (PTLD). A chronic high load (CHL), as indicated by long-term high EBV DNA levels after transplantation, has been associated with an enhanced risk of PTLD. We aimed to evaluate incidence, time of occurrence, risk factors, and outcome of EBV CHL carrier state after pediatric renal transplantation.MethodsA retrospective study of 58 children aged 1–17 years (median 10), who underwent renal transplantation between January 2004 and June 2017 at a single medical center. EBV IgG antibodies in serum were analyzed before and yearly after transplantation. EBV DNA in whole blood were analyzed weekly for the first 3 months post-transplant, monthly up to 1 year and then at least once yearly. CHL was defined as EBV DNA ≥ 4.2 log10 Geq/ml in > 50% of the samples during ≥ 6 months.ResultsAt transplantation, 31 (53%) patients lacked EBV IgG and 25 (81%) of them developed primary EBV infection post-transplant. Of the 27 seropositive patients, 20 (74%) experienced reactivation of EBV. Altogether, 14 (24%) children developed CHL, starting at a median of 69 days post-transplant and lasting for a median time of 2.3 years (range 0.5–6.5), despite reduction of immunosuppression. Patients with CHL were younger and 11/14 were EBV seronegative at transplantation. No child developed PTLD during median clinical follow-up of 7.8 years (range 0.7–13).ConclusionsCHL was frequent, long lasting, and occurred mainly in young transplant recipients. The absence of PTLD suggests that monitoring of EBV DNA to guide immunosuppression was effective.

Highlights

Epstein-Barr virus (EBV) infection may constitute a serious risk for EBV-associated complications in transplant recipients, whose cellular and humoral response is compromised by immunosuppressive therapy [1, 2]
The present study suggests that close monitoring of EBV DNA levels post-transplant can facilitate the identification of patients at risk of developing chronic high load (CHL) and post-transplant lymphoproliferative disorder (PTLD)
The absence of PTLD in our patients suggests that monitoring of EBV DNA to guide immunosuppression may be effective in reducing the risk of PTLD

Summary

Introduction

Epstein-Barr virus (EBV) infection may constitute a serious risk for EBV-associated complications in transplant recipients, whose cellular and humoral response is compromised by immunosuppressive therapy [1, 2]. EBV-associated PTLD in pediatric renal transplant recipients has been associated with graft loss [19] and has a mortality rate of 32–48% [15, 20, 21]. Barr virus (EBV) infections can induce post-transplant lymphoproliferative disorder (PTLD). A chronic high load (CHL), as indicated by long-term high EBV DNA levels after transplantation, has been associated with an enhanced risk of PTLD. We aimed to evaluate incidence, time of occurrence, risk factors, and outcome of EBV CHL carrier state after pediatric renal transplantation. EBV DNA in whole blood were analyzed weekly for the first 3 months post-transplant, monthly up to 1 year and at least once yearly. 14 (24%) children developed CHL, starting at a median of 69 days post-transplant and lasting for a median time of 2.3 years (range 0.5–6.5), despite reduction of immunosuppression. The absence of PTLD suggests that monitoring of EBV DNA to guide immunosuppression was effective

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