Alveolar macrophage lipid burden correlates with clinical improvement in patients with Pulmonary Alveolar Proteinosis

Abstract

Pulmonary alveolar proteinosis (PAP) is a life-threatening rare lung syndrome characterized by the accumulation of surfactant and lipid-loaded macrophages within the alveoli for which there is no cure and no approved therapies. The clinical diagnosis of PAP, often made by invasive lung biopsies and/or cytology of bronchoalveolar lavage fluid does not identify the underlying cause of disease. In addition, no biomarkers exist to inform prognosis or therapeutic options in PAP. We now report on the use of comprehensive mass spectrometry to profile and define the lipid signature of alveolar macrophages obtained from PAP patients. In addition, we quantify how these macrophage-associated lipids change during clinical treatment. Our studies demonstrate that clinical improvement in treated PAP patients is associated with a decrease in total lipid content, indicating that levels of these macrophage-associated lipids correlate with the severity of the disease.