Bronchoalveolar Lavage Fluid Proteome in Bronchiolitis Obliterans Syndrome: Possible Role for Surfactant Protein A in Disease Onset

Bronchiolitis obliterans syndrome (BOS) affects long-term survival of lung transplant (Tx) recipients (LTRs), with no consistently effective treatment strategy. Identifying early markers of BOS is of paramount importance for improving graft survival. Methods: We used 2-dimensional gel electrophoresis and protein identification by mass spectrometry to compare the protein profile of bronchoalveolar lavage fluid (BALf) in two groups of LTRs: one composed of patients with BOS and the other composed of patients with good graft function at 5 years post-surgery (stable LTRs). Based on the hypothesis that only proteins of lung origin could represent reliable BOS markers, we also evaluated paired plasma samples. Proteins of interest were also assessed in the BALf of control subjects and results confirmed by dot- blot analysis. Results: Among 11 differentially expressed proteins, we identified 2 locally produced factors: peroxiredoxin II (PRXII), exclusively expressed in BOS; and surfactant protein A (SP-A), expressed consistently less in BOS patients than in stable LTRs. PRXII expression was never observed in BALf from control subjects, whereas SP-A was present in higher amounts compared with stable LTRs and BOS patients. Finally, the time course of SP-A was studied in 5 LTRs who subsequently developed BOS. A reduction in BALf SP-A content was detectable early after Tx, preceding BOS onset in 4 of 5 patients. Conclusions: Our results suggest that testing SP-A levels in BALf could predict LTR patients who are at higher risk of BOS development.