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

Abstract

Background Epstein-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. Methods A 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 log 10 Geq/ml in > 50% of the samples during ≥ 6 months. Results At transplantation, 31 (53%) patients lacked EBV IgG and 25 (81%) of them developed primary EBV infection posttransplant. 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). Conclusions CHL 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.

Long-Term Care of the Pediatric Kidney Transplant Recipient

“…Very small pediatric recipients often must successfully perfuse an adult donor kidney, and the transplanted kidney must accommodate large changes in body size. Viral infections such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), and polyoma virus may have more severe consequences in infection-naïve pediatric recipients (4)(5)(6)(7)(8). Furthermore, not only must pediatric transplant recipients get through the high-risk interval in the early post-transplant period, but they must also traverse a second high-risk period of adolescence and young adulthood, during which immunologic risk may be heightened and medication adherence may be suboptimal (9)(10)(11).…”

Screening and Management of PTLD

“…3,[5][6][7]10,31,62 Approximately 20% of EBV-seronegative pediatric SOT recipients demonstrate persistently elevated levels of EBV DNAemia (defined as chronic high load) following resolution of primary EBV infection or PTLD. [63][64][65][66] Incidence of such phenomenon is less clear in adult SOT recipients but has been reported. [67][68][69] Among the pediatric SOT recipients, heart and intestinal transplant recipients with evidence of chronic elevated EBV DNAemia have increased risk of developing late PTLD, while this risk has not been identified in kidney and liver transplant recipients with chronic high loads.…”

“…Evidence of EBV DNAemia in pediatric kidney transplant is reported to range between 20% and 60%. 65,66,[86][87][88] Controversial findings have been reported regarding risk of rejection and graft survival. 87,[89][90][91] In a large, multicenter prospective trial on the epidemiology of EBV infection including over 100 pediatric kidney transplant recipients, EBV DNAemia was evaluated in the whole blood at 6 wk then every 3 mo during the first-y posttransplant.…”

Non-Hodgkin lymphoma after pediatric kidney transplantation

“…Reactivation of EBV infection in EBV-positive (at transplantation) children is variable. It was reported within a range of <20 to 74% [ 27 , 28 ].…”

“…Young age (median age of 2 vs. 12 years; p = 0.0001) was associated with this phenomenon. Notably, none of these patients developed PTLD [ 45 ]. It must be stressed that a significant conflict of interest exists between the reduction of immunosuppression, aimed to control the development of PTLD (or lymphoma) and the general purpose of organ transplantation, as the former increases the risk of acute and chronic rejection, graft loss, and poorer patient survival.…”