Development of Non-HLA Antibodies and Their Association With Antibody-Mediated Rejection in Pediatric Kidney Transplant Recipients

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.