Early BAL microRNA Signatures Delineate Biological Trajectories Towards CLAD After Lung Transplantation

Area of Science:

• Transplantation immunology
• Molecular biology
• Pulmonary medicine

Background:

• Chronic lung allograft dysfunction (CLAD) is a major barrier to long-term lung transplant survival.
• Early molecular changes in the graft may precede clinical signs of dysfunction, but their role is unclear.

Purpose of the Study:

• To investigate early bronchoalveolar lavage (BAL)-derived microRNA (miRNA) profiles after lung transplantation.
• To correlate these early miRNA signatures with long-term clinical outcomes, including CLAD development and specific phenotypes (BOS, RAS).

Main Methods:

• Longitudinal BAL sampling at 7 days, 15 days, and 3 months post-lung transplantation in 16 recipients.
• Analysis of BAL-derived miRNA profiles.
• Correlation of miRNA signatures with long-term clinical outcomes (mean 98 months follow-up).

Main Results:

• Distinct early miRNA signatures were identified within weeks post-transplantation.
• Specific miRNAs (let-7e-5p, miR-30d-3p) were associated with subsequent CLAD development.
• Differential miRNA expression patterns distinguished trajectories toward BOS or RAS.
• Enrichment analysis implicated innate immunity, hypoxia, tissue remodeling, and PI3K-mTOR signaling pathways.

Conclusions:

• Early BAL-derived miRNA profiles may serve as biomarkers for predicting long-term CLAD risk and phenotype.
• These molecular signatures may reflect distinct early graft states influencing clinical trajectories.
• Acute rejection rates did not differ between CLAD and stable graft groups, suggesting other early factors are critical.