Front Med (Lausanne). 2026 Aug 17;13:1884832. doi: 10.3389/fmed.2026.1884832. eCollection 2026.
ABSTRACT
Antibody-mediated rejection (AMR) is a serious post-lung transplant (LTx) complication with a challenging diagnosis. Histopathological findings associated with AMR include variable degrees of capillary inflammation, endotheliitis, and diffuse alveolar damage/organizing pneumonia. AMR has been historically related to anti-HLA donor-specific antibodies (DSA), while the role of non-HLA antibodies remains debated. We report the case of a 15-year-old male undergoing bilateral LTx for cystic fibrosis. Twenty days later, the patient developed moderate acute cellular rejection (ACR); in samples not affected by ACR, diffuse edema, capillary inflammation, and high p-S6RP expression scores were observed in macrophages, endothelial and epithelial cells. Anti-HLA class II DSA [maximum median fluorescence intensity (MFI): 10434] supported a diagnosis of mixed cellular/humoral rejection. After steroid therapy, DSA markedly decreased (maximum MFI: 1534), and ACR resolved, whereas persistent capillary inflammation and high p-S6RP expression in all cell types characterized sequential biopsies, raising suspicion for ongoing subclinical AMR. The persistence of these morphological features, together with sustained p-S6RP overexpression, prompted extended immunological testing, which revealed markedly elevated antibodies against endothelin type A receptor and angiotensin II type 1 receptor (>40 U/mL) in the patient follow-up. This case underscores the pivotal role of histopathological findings in multidisciplinary decision-making and highlights the importance of extended immunological screening. Our findings further support the emerging pathogenic relevance of non-HLA antibodies in the development and persistence of AMR in LTx recipients. The patient ultimately died 25 months after transplantation from progressive chronic lung allograft dysfunction.
PMID:42676341 | PMC:PMC13526557 | DOI:10.3389/fmed.2026.1884832
