ORIGINAL RESEARCH
Transpl. Int.
Volume 38 - 2025 | doi: 10.3389/ti.2025.14463
This article is part of the Special IssueAnti-HLA DSA and Beyond: deciphering the immunological mechanisms driving chronic rejectionView all 13 articles
Development of non-HLA antibodies and their association with antibody-mediated rejection in pediatric kidney transplant recipients
Franziska Schmidt1Murielle Verboom2Michael Hallensleben2Alexander Braumann3Jens Drube4Lena Brunkhorst1Dieter Haffner1Anette Melk1
Nele Kanzelmeyer1*- 1Clinic for Pediatric Kidney, Liver and Metabolic Diseases, Center for Pediatrics and Adolescent Medicine, Hannover Medical School, Hannover, Lower Saxony, Germany
- 2Institute for Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Lower Saxony, Germany
- 3Institute for Mathematical Stochastics, Technische Universität Braunschweig, Braunschweig, Germany, Braunschweig, Germany
- 4Department of Pediatric Kidney, Liver, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany, Hannover, Germany
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Antibody-mediated rejection (ABMR) is the leading cause of long-term graft loss in pediatric kidney transplantation (KTx). While donor-specific HLA antibodies are established contributors, emerging evidence suggests a role for non-HLA antibodies in ABMR pathogenesis. In this descriptive study, we analyzed 60 non-HLA antibodies in 77 pediatric KTx recipients using serum samples collected pre-transplant, post-transplant, and at ABMR diagnosis. During a median follow-up of 4.83 years, 29.8% developed ABMR, with a median onset of 3.67 years. Non-HLA antibody presence prior to KTx was not influenced by pre-transplant dialysis; over half of the patients already had >15 positive non-HLA antibodies. The cumulative antibody profile remained stable 1–2 years post-KTx, with no association between late ABMR and antibody strength or breadth. However, ACTIN (higher risk) and CGB5 (lower risk) at 1–2 years post-KTx, as well as SNRPB2 pre-transplant, were significantly associated with ABMR (p < 0.05). IL-21 levels increased in controls over time (p < 0.05), although driven by five patients with notably high levels.Our findings support a potential involvement of non-HLA antibodies in pediatric ABMR. Nevertheless, larger studies are needed to validate the predictive value of individual non-HLA antibodies for clinical application.
Keywords: non-HLA antibodies, Antibody-mediated rejection, pediatric kidney transplantation, graft loss, pediatric kidney failure
Received: 07 Feb 2025; Accepted: 09 Jun 2025.
Copyright: © 2025 Schmidt, Verboom, Hallensleben, Braumann, Drube, Brunkhorst, Haffner, Melk and Kanzelmeyer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Nele Kanzelmeyer, Clinic for Pediatric Kidney, Liver and Metabolic Diseases, Center for Pediatrics and Adolescent Medicine, Hannover Medical School, Hannover, 30625, Lower Saxony, Germany
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