Are Intravenous Immunoglobulins Effective in Preventing Primary EBV Infection in Pediatric Kidney Transplant Recipients?

Background and

Objectives

Primary Epstein-Barr virus (EBV) infection in pediatric kidney transplant recipients with donor/recipient mismatch (D+/R-) carries the highest risk of post-transplant lymphoproliferative disorder (PTLD). Current prophylactic strategies are not standardized. Intravenous immunoglobulins (IVIG), containing anti-EBV antibodies, have been proposed as a potential preventive option, but evidence is lacking. This single-center retrospective case-control study evaluated the efficacy of serial IVIG administration in preventing primary EBV infection and promoting long-term immunity in this high-risk population. Materials and

Methods

We retrospectively analyzed 26 pediatric kidney transplant recipients (age 1-18 years) with EBV D+/R- mismatch and a median follow-up of 7.5 years. Fourteen patients received scheduled IVIG infusions (200 mg/kg monthly for six months post-transplantation), while twelve received no EBV-directed prophylaxis. The primary endpoint was the cumulative incidence of primary EBV infection, defined as EBV-DNA > 1000 copies/mL in peripheral blood. The secondary endpoint was Epstein-Barr Nuclear Antigen-Immunoglobulin G (EBNA-IgG) seroconversion.

Results

Patients receiving IVIG were significantly younger than controls (median age 4.2 vs. 10.8 years, p = 0.01). No significant variations were observed between groups in renal function or immunosuppressive levels during follow-up. IVIG prophylaxis was unexpectedly linked to a higher cumulative incidence of EBV infection compared with controls (64% vs. 25%, p = 0.047). Time-to-event analysis confirmed an increased, although not statistically significant, risk of EBV acquisition in the IVIG group (Hazard Ratio [HR] 3.24, 95% Confidence Interval [CI] 0.87-12.01; p = 0.079). EBV-specific immunity, assessed by EBNA-IgG seroconversion, was comparable between groups (HR 1.78; p = 0.45), confirming no immunological advantage of IVIG. One IVIG-treated patient (7.1%) developed PTLD, while none did in the control group.

Conclusions

Scheduled IVIG administration during the first six months after transplantation does not constitute an effective strategy to prevent primary EBV infection or to enhance long-term immunity in high-risk EBV D+/R- pediatric kidney recipients and may even increase susceptibility to viral acquisition. These findings argue against the use of IVIG as EBV prophylaxis in this population.