Antibody-mediated rejection (AMR) in pediatric lung transplantation-Current state and future directions

Lung transplantation is considered as the ultimate therapy for children with advanced pulmonary disease. International data show a median conditional 1-year post-transplantation survival of 9.1 years. Recently, antibody-mediated rejection (AMR) has increasingly been recognized as an important cause of allograft dysfunction although pediatric reports are still scarce. Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) are known to play a role in AMR development post-transplant but AMR pathogenesis is still poorly understood. Central to the concept of pulmonary AMR is immune activation with the production of allo-specific B-cells and plasma cells directed against donor lung antigens. The frequency of pulmonary AMR in children is currently unknown. Due to the lack of AMR data in children, the diagnostic approach for pediatric pulmonary AMR is solely based on adult literature. This personal viewpoint article evaluates the rational for the creation of age-based thresholds for different diagnostic categories of pulmonary AMR and data on the management of pulmonary AMR in children. To the authors' knowledge, there have been no randomized controlled trials comparing different management regimes in pulmonary AMR, and thus, management and treatment algorithms for pulmonary AMR in children are only extrapolated from adults. To advance the knowledge of AMR in children, the authors propose that children be included in collaborative, multi-center trials. It is vital that future decisions on internationally agreed upon guidelines for pulmonary AMR take its impact on children into consideration. Research is needed to fill the current knowledge gaps in the field of pulmonary AMR in children focused on optimizing outcomes.