Proteome analysis of bronchoalveolar lavage in pulmonary langerhans cell histiocytosis

In this study we used a proteomic approach to analyze BAL protein composition of patients with PLCH and of healthy smoker and non-smoker controls to obtain insights into the pathogenetic mechanisms of the disease, to study the effect of cigarette smoking on susceptibility to PLCH and to identify potential new biomarkers.Two-dimensional electrophoresis and image analysis revealed proteins that were differently expressed (quantitatively and qualitatively) in the three groups of subjects. The proteins were identified by mass spectrometry and have various functions (antioxidant, proinflammatory, antiprotease) and origins (plasma, locally produced, etc.). Many, such as protease inhibitors (human serpin B3) and antioxidant proteins (glutathione peroxidase and thioredoxin) are already linked to PLCH pathogenesis, whereas other proteins have never been associated with the disease. Interestingly, numerous proteolytic fragments of plasma proteins (including kininogen-1 N fragments and haptoglobin) were also identified and suggest increased proteolytic activity in this inflammatory lung disease. Differences in protein expression were found between the three groups and confirmed by Principal Component Analysis (PCA).Analysis of BAL proteomes of PLCH patients and of smoker and non-smoker controls also proved to be useful for researching the pathogenetic mechanisms and for identifying biomarkers of this rare diffuse lung disease.Pulmonary Langerhans cell histiocytosis (PLCH) is a rare granulomatous disorder characterized by uncontrolled proliferation and infiltration of CD1+ Langerhans cells (LCs) in the lung. It has been associated with smoking and prevalently affects young adults [1,2]. The pathogenesis of PLCH is unclear. The bronchiolar distribution of lesions suggests that an inhaled antigen, such as cigarette smoke, may be involved, since 90% of cases are smokers [3]. The correlation between PLCH and smoking is corroborated by recent studies demonstrating that acute tobacco