Apparentness of Unseen Rejection Episodes Post Lung rLTx Is Reliably Enabled by ddcfDNA Detection

ABSTRACT ddcfDNA emerged as a biomarker for post‐transplantation management strategies. Lung retransplant recipients represent a particularly vulnerable patient population with an increased risk of allograft injury. The demand for understanding if ddcfDNA levels differ between primary lung transplant recipients and lung retransplant recipients becomes obvious. Eight lung retransplant recipients and 50 primary lung transplant recipients with comparable HLA Class I and Class II mismatch scores were included in this retrospective study. During post‐transplant monitoring, ddcfDNA results were evaluated alongside data on patient humoral immune responses pre‐ and post‐transplantation. Antibody profiles of lung retransplant recipients did not differ significantly from those of their primary transplant comparisons. However, significantly higher ddcfDNA levels were observed in the retransplant cohort (median: 1.463%, IQR: 0.810–2.745) compared with primary transplant cohort (median: 0.550%, IQR: 0.338–0.935), U  = 100.50, Z  = −2.24, p  = 0.012, r  = 0.29. We identified that lung retransplant recipients exhibit increased allograft injury not solely attributable to humoral responses. Our study highlights that these patients face a higher immunological risk and supports the need for closer clinical follow‐up using a resilient biomarker such as ddcfDNA. Incorporating ddcfDNA as a surrogate marker into post‐transplant monitoring would provide early and unambiguous insights into allograft rejection, enabling prompt interventions to prevent unfavourable outcomes in this particularly fragile patient group.