Sangermano Maria, Soncin Vittoria, Auciello Maria, Ciabattoni Francesco, Negrisolo Susanna, Marinelli Elena, Bertazza Partigiani Nicola, Benetti Elisa
Pediatric Nephrology, Department of Women's and Children's Health, Padua University Hospital, 35128 Padua, Italy.
Laboratory of Immunopathology and Molecular Biology of the Kidney, Department of Women's and Children's Health, Padua University Hospital, 35128 Padua, Italy.
Int J Mol Sci. 2025 Jun 19;26(12):5870. doi: 10.3390/ijms26125870.
While the pathogenic role of donor-specific anti-HLA antibodies (DSAs) in long-term immune-mediated injury after kidney transplantation is well established, the clinical relevance of non-donor-specific antibodies (nDSAs), also detected in transplant recipients, remains a subject of debate. This retrospective study evaluated the prognostic value of nDSAs in 92 pediatric kidney transplant recipients (89.1%, 9.8%, and 1.1% for first, second, and third transplants, respectively) at the University Hospital of Padua between January 2015 and December 2022, investigating the association between antibody development and clinical outcomes, including graft function, rejection episodes, and viral infections. Clinical, immunological, virological, and histopathological data were collected at 6, 12, and 24 months post-transplant. Antibody prevalence increased over time, with nDSAs being more frequent than DSAs at all timepoints. The combined presence of DSAs and nDSAs significantly increased the risk of ABMR (HR = 45.10; < 0.001). Isolated nDSAs and DSAs were also associated with an increased risk of ABMR (HR = 6.43 and 12.10, respectively), suggesting a synergistic alloimmune effect. Viral infections also emerged as relevant cofactors in humoral alloimmunity. EBV viremia and intrarenal Parvovirus B19 (PVB19) infection were significantly associated with ABMR, with PVB19 also correlating with nDSA formation. In conclusion, integrated immunological and virological monitoring may support risk stratification and guide individualized post-transplant management. Larger multicenter studies are warranted to define the long-term impact of nDSAs in pediatric kidney transplantation.
虽然供体特异性抗HLA抗体（DSA）在肾移植后长期免疫介导损伤中的致病作用已得到充分证实，但在移植受者中也检测到的非供体特异性抗体（nDSA）的临床相关性仍存在争议。这项回顾性研究评估了2015年1月至2022年12月期间在帕多瓦大学医院的92名小儿肾移植受者（首次、第二次和第三次移植分别占89.1%、9.8%和1.1%）中nDSA的预后价值，调查了抗体产生与临床结局之间的关联，包括移植肾功能、排斥反应发作和病毒感染。在移植后6、12和24个月收集临床、免疫学、病毒学和组织病理学数据。抗体患病率随时间增加，在所有时间点nDSA都比DSA更常见。DSA和nDSA的联合存在显著增加了ABMR的风险（HR = 45.10；<0.001）。单独的nDSA和DSA也与ABMR风险增加相关（HR分别为6.43和12.10），提示存在协同的同种异体免疫效应。病毒感染也成为体液同种异体免疫中的相关辅助因素。EBV病毒血症和肾内细小病毒B19（PVB19）感染与ABMR显著相关，PVB19也与nDSA形成相关。总之，综合的免疫学和病毒学监测可能有助于风险分层并指导个体化的移植后管理。需要开展更大规模的多中心研究来确定nDSA在小儿肾移植中的长期影响。
