Proteomic analysis of bronchoalveolar lavage fluid after lung transplantation associates stable allograft function with less lung damage at 12 months.

INTRODUCTION

Freedom from chronic lung allograft dysfunction (CLAD) is a key objective after lung transplantation, yet predicting its onset remains challenging. This study investigated whether early proteomic changes in bronchoalveolar lavage fluid can differentiate between patients maintaining stable graft function at 36 months and those developing CLAD within the first year. Additionally, findings were compared to proteomic data from non-transplanted individuals.

METHODS

Bronchoalveolar lavage fluid samples were collected at 1 month and 12 months post-transplant from 43 lung transplant recipients together with clinical parameters. Proteomic analysis was performed using mass spectrometry with label-free quantification for global protein profiling and heavy-labelled peptides for absolute quantification of mucins and related proteins. Differentially expressed proteins were identified and analysed through pathway enrichment to explore biological mechanisms associated with CLAD.

RESULTS

No significant proteomic differences were detected at 1 month. By 12 months, 63 proteins were differentially expressed between patients who developed early CLAD and those with stable function. Mucin levels declined in stable patients but remained elevated in both groups compared to healthy controls. Cartilage acidic protein 1 was significantly higher in stable patients at 12 months and correlated with better pulmonary function. Pathway analysis linked several proteins altered in patients with CLAD to networks associated with lung injury and remodelling.

CONCLUSION

Protein profiles in bronchoalveolar lavage fluid that resemble those of healthy lungs are associated with sustained graft function, while persistent expression of lung injury markers is associated with early CLAD. This suggests an adaptive process is needed for long-term post-transplant success.