{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T15:32:33Z","timestamp":1762183953183,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T00:00:00Z","timestamp":1762041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Primary Epstein\u2013Barr virus (EBV) infection in pediatric kidney transplant recipients with donor\/recipient mismatch (D+\/R\u2212) 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\u2013control 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\u201318 years) with EBV D+\/R\u2212 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 &gt; 1000 copies\/mL in peripheral blood. The secondary endpoint was Epstein\u2013Barr 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\u201312.01; 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\u2212 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.<\/jats:p>","DOI":"10.3390\/medicina61111967","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:55:22Z","timestamp":1762178122000},"page":"1967","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Are Intravenous Immunoglobulins Effective in Preventing Primary EBV Infection in Pediatric Kidney Transplant Recipients?"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6113-9312","authenticated-orcid":false,"given":"Nicola","family":"Bertazza Partigiani","sequence":"first","affiliation":[{"name":"Pediatric Nephrology, Department of Women\u2019s and Children\u2019s Health, Padua University Hospital, 35128 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3428-5772","authenticated-orcid":false,"given":"Veronica","family":"Bertozzi","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Department of Women\u2019s and Children\u2019s Health, Padua University Hospital, 35128 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7391-7019","authenticated-orcid":false,"given":"Maria","family":"Sangermano","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Department of Women\u2019s and Children\u2019s Health, Padua University Hospital, 35128 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8939-6376","authenticated-orcid":false,"given":"Elisa","family":"Benetti","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Department of Women\u2019s and Children\u2019s Health, Padua University Hospital, 35128 Padua, Italy"},{"name":"Laboratory of Immunopathology and Molecular Biology of the Kidney, Pediatric Research Institute, Department of Women\u2019s and Children\u2019s Health, Padua University Hospital, 35128 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jcv.2018.03.001","article-title":"Primary Epstein-Barr virus infection","volume":"102","author":"Dunmire","year":"2018","journal-title":"J. Clin. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e13652","DOI":"10.1111\/ctr.13652","article-title":"AST Infectious Diseases Community of Practice. Post-transplant lymphoproliferative disorders, Epstein-Barr virus infection, and disease in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice","volume":"33","author":"Allen","year":"2019","journal-title":"Clin. Transplant."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Baker, A., Frauca Remacha, E., Torres Canizales, J., Bravo-Gallego, L.Y., Fitzpatrick, E., Alonso Melgar, A., Mu\u00f1oz Bartolo, G., Garcia Guereta, L., Ramos Boluda, E., and Mozo, Y. (2021). Current Practices on Diagnosis, Prevention and Treatment of Post-Transplant Lymphoproliferative Disorder in Pediatric Patients after Solid Organ Transplantation: Results of ERN TransplantChild Healthcare Working Group Survey. Children, 8.","DOI":"10.3390\/children8080661"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S1386-6532(01)00149-4","article-title":"Epstein-Barr virus (EBV) infection in infancy","volume":"21","author":"Chan","year":"2001","journal-title":"J. Clin. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kuri, A., Jacobs, B.M., Vickaryous, N., Pakpoor, J., Middeldorp, J., Giovannoni, G., and Dobson, R. (2020). Epidemiology of Epstein-Barr virus infection and infectious mononucleosis in the United Kingdom. BMC Public Health, 20.","DOI":"10.1186\/s12889-020-09049-x"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1007\/s00467-024-06522-2","article-title":"Prevention of post-transplant lymphoproliferative disorder in pediatric kidney transplant recipients","volume":"40","author":"Pollack","year":"2025","journal-title":"Pediatr. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1034\/j.1399-3062.2001.003002097.x","article-title":"The role of antiviral and immunoglobulin therapy in the prevention of Epstein-Barr virus infection and post-transplant lymphoproliferative disease following solid organ transplantation","volume":"3","author":"Green","year":"2001","journal-title":"Transpl. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1111\/j.1600-6143.2006.01394.x","article-title":"CMV-IVIG for prevention of Epstein Barr virus disease and posttransplant lymphoproliferative disease in pediatric liver transplant recipients","volume":"6","author":"Green","year":"2006","journal-title":"Am. J. Transplant."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1681\/ASN.2008030287","article-title":"New equations to estimate GFR in children with CKD","volume":"20","author":"Schwartz","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1097\/TP.0000000000002366","article-title":"A 2018 reference guide to the Banff classification of renal allograft pathology","volume":"102","author":"Roufosse","year":"2018","journal-title":"Transplantation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1111\/j.1600-6143.2008.02528.x","article-title":"Valganciclovir dosing according to body surface area and renal function in pediatric solid organ transplant recipients","volume":"9","author":"Vaudry","year":"2009","journal-title":"Am. J. Transplant."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e13512","DOI":"10.1111\/ctr.13512","article-title":"Cytomegalovirus in solid organ transplant recipients: Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice","volume":"33","author":"Razonable","year":"2019","journal-title":"Clin. Transplant."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bertazza Partigiani, N., Negrisolo, S., Carraro, A., Marzenta, D., Manaresi, E., Gallinella, G., Barzon, L., and Benetti, E. (2023). Pre-Existing Intrarenal Parvovirus B19 Infection May Relate to Antibody-Mediated Rejection in Pediatric Kidney Transplant Patients. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119147"},{"key":"ref_14","first-page":"e13591","article-title":"The IPTA Nashville Consensus Conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: III\u2014Consensus guidelines for Epstein-Barr virus load and other biomarker monitoring","volume":"23","author":"Preiksaitis","year":"2019","journal-title":"Pediatr. Transplant."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1111\/j.1600-6143.2011.03893.x","article-title":"Associations between EBV serostatus and organ transplant type in PTLD risk: An analysis of the SRTR National Registry Data in the United States","volume":"12","author":"Dharnidharka","year":"2012","journal-title":"Am. J. Transplant."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"506","DOI":"10.3389\/fonc.2020.00506","article-title":"Biological Difference Between Epstein-Barr Virus Positive and Negative Post-transplant Lymphoproliferative Disorders and Their Clinical Impact","volume":"10","author":"Ferla","year":"2020","journal-title":"Front Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1056\/NEJM200008173430707","article-title":"Epstein-Barr virus infection","volume":"343","author":"Cohen","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15088","DOI":"10.1038\/nrdp.2015.88","article-title":"Post-transplant lymphoproliferative disorders","volume":"2","author":"Dharnidharka","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"305","DOI":"10.2174\/1573396320666230801091558","article-title":"Infectious Mononucleosis: An Updated Review","volume":"20","author":"Leung","year":"2024","journal-title":"Curr. Pediatr. Rev."},{"key":"ref_20","first-page":"391","article-title":"Transfusion-associated viral infections","volume":"17","author":"Baldwin","year":"1987","journal-title":"Curr. Probl. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/trf.16149","article-title":"Transfusion-related Epstein-Barr virus (EBV) infection: A multicenter prospective cohort study among pediatric recipients of hematopoietic stem cell transplants (TREASuRE study)","volume":"61","author":"Buteau","year":"2021","journal-title":"Transfusion"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.1111\/j.1537-2995.2012.03611.x","article-title":"Transfusion-related Epstein-Barr virus infection among stem cell transplant recipients: A retrospective cohort study in children","volume":"52","author":"Trottier","year":"2012","journal-title":"Transfusion"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/j.1399-3062.2005.00110.x","article-title":"Induction of pre-transplant Epstein-Barr virus (EBV) infection by donor blood transfusion in EBV-seronegative recipients may reduce risk of post-transplant lymphoproliferative disease in adolescent renal transplant patients: Report of two cases","volume":"7","author":"Babel","year":"2005","journal-title":"Transpl. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Cheyssac, E., Savadogo, H., Lagoutte, N., Baudouin, V., Charbit, M., Novo, R., Sellier-Leclerc, A.L., Fila, M., Decramer, S., and Merieau, E. (2023). Valganciclovir is not associated with decreased EBV infection rate in pediatric kidney transplantation. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.1085101"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e13382","DOI":"10.1111\/petr.13382","article-title":"Cytomegalovirus and Epstein-Barr virus infections among pediatric kidney transplant recipients at a center using universal Valganciclovir Prophylaxis","volume":"23","author":"Paulsen","year":"2019","journal-title":"Pediatr. Transplant."},{"key":"ref_26","first-page":"e14350","article-title":"The IPTA Nashville consensus conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: II-consensus guidelines for prevention","volume":"26","author":"Green","year":"2022","journal-title":"Pediatr. Transplant."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1111\/ajt.14020","article-title":"The role of antiviral prophylaxis for the prevention of Epstein-Barr virus-associated posttransplant lymphoproliferative disease in solid organ transplant recipients: A systematic review","volume":"17","author":"AlDabbagh","year":"2017","journal-title":"Am. J. Transplant."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1111\/tid.12605","article-title":"Pretransplant prophylactic rituximab to prevent Epstein-Barr virus (EBV) viremia in EBV-seronegative kidney transplant recipients from EBV-seropositive donors: Results of a pilot study","volume":"18","author":"Schachtner","year":"2016","journal-title":"Transpl. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e14743","DOI":"10.1111\/petr.14743","article-title":"Effect of pre-emptive rituximab on EBV DNA levels and prevention of post-transplant lymphoproliferative disorder in pediatric kidney transplant recipients: A case series from the pediatric nephrology research consortium","volume":"28","author":"Ashoor","year":"2024","journal-title":"Pediatr. Transplant."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e14113","DOI":"10.1111\/petr.14113","article-title":"Use of Rituximab for persistent EBV DNAemia, and Its effect on donor-specific antibody development in pediatric renal transplant recipients: A case series","volume":"25","author":"Puliyanda","year":"2021","journal-title":"Pediatr. Transplant."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Marja\u0144ska, A., Pogorza\u0142a, M., Dziedzic, M., Czy\u017cewski, K., Richert-Przygo\u0144ska, M., D\u0119bski, R., Bogiel, T., and Styczy\u0144ski, J. (2024). Impact of prophylaxis with rituximab on EBV-related complications after allogeneic hematopoietic cell transplantation in children. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1427637"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/11\/1967\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T14:45:52Z","timestamp":1762181152000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/11\/1967"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,2]]},"references-count":31,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["medicina61111967"],"URL":"https:\/\/doi.org\/10.3390\/medicina61111967","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,2]]}}}