Background and Objectives: Primary Epstein–Barr virus (EBV) infection in pediatric kidney transplant recipients with donor/recipient mismatch (D+/R−) carries the high-est risk of post-transplant lymphoproliferative disorder (PTLD). Current prophylactic strategies are not standardized. Intravenous immunoglobulins (IVIG), containing an-ti-EBV antibodies, have been proposed as a potential preventive option, but evidence is lacking. This single-center case-control study evaluated the efficacy of serial IVIG ad-ministration 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 anti-EBNA IgG seroconversion. Results: IVIG prophylaxis was unexpectedly associated with a higher cumulative incidence of EBV infection com-pared with controls (64% vs. 25%, p = 0.047). Time-to-event analysis confirmed an in-creased, 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 Epstein–Barr Nuclear Antigen-Immunoglobulin G (EBNA-IgG) seroconversion, was comparable between groups (HR 1.78; p = 0.45), con-firming no immunological advantage of IVIG. One IVIG-treated patient (7.1%) devel-oped PTLD, while none occurred 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 susceptibil-ity to viral acquisition. These findings argue against the use of IVIG as EBV prophylax-is in this population.

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.