Deleterious impact of C3d-binding donor-specific anti-HLA antibodies after pediatric liver transplantation

Background The prevalence and clinical impact of anti-HLA donor-specific antibodies (DSA) after liver transplantation (LT) have not been extensively studied, especially in pediatric population. Methods The present cross-sectional study included 100 patients who underwent a first LT in childhood. Anti HLA immunization study was performed at a single time point during routine follow-up using Luminex® single antigen tests with classical anti-IgG conjugate and anti-C3d conjugate. Results The main indication for LT was biliary atresia (52%) and median age at LT was 4.6 years. The median time between LT and DSA assessment was 7.8 years (range 1–21 years). DSA was identified in twenty-four patients (24%) after LT, with a prevalence of 8%, 28%, 33%, 50%, respectively 0–5 years, 5–10 years, 10–15 years and > 15 years after LT. DSA were mainly class II (23/24) with a mean MFI of 9.731 ± 5.489 and 18 (79.3%) were C3d-binding DSA. Multivariate analysis disclosed that time elapsed since LT (p < 0.01) and history of fulminant hepatitis (p = 0.04) were significantly associated with a higher rate of DSA. Liver function tests (at time of DSA assessment) were not different according to the presence or not of DSA (or C3d-binding DSA). Regarding histology, the DSA group had a higher rate of chronic rejection, cirrhosis and centrilobular fibrosis or cirrhosis. In addition, patients with C3d-binding DSA and high MFI (> 10,000) had a significant poorer long-term graft survival (p = 0.03). Conclusion In our pediatric cohort of LT, prevalence of DSA was high and increased regularly with time. Presence of C3d positive-DSA with high MFI was associated with a higher rate of graft loss.