Am J Respir Crit Care Med 2019 Apr 19. Epub 2019 Apr 19.
Regensburg University Hospital, Regensburg, Germany.
Rationale: Pulmonary alveolar proteinosis is characterized by filling of the alveolar spaces by lipoprotein rich material of ill-defined composition, and which is caused by molecularly different and often rare diseases occurring from birth to old age.
Objectives: Quantitative lipidomic analysis of lipids and surfactant proteins A, B and C from lavage fluids of patients with different causes of proteinosis in comparison to healthy contols.
Methods: During the last decades we collected alveolar lavage samples from patients with PAP due to autoantibodies against GMCSF, genetic mutations in CSF2RA, MARS, FARSB, NPC2 and secondary to myeloid leukemia. Their lipid composition was quantified.
Results: Free cholesterol was largely increased by 60-fold and cholesterol esters by 24-fold. There was an excessive more than 130-fold increase in ceramide and other sphingolipids. Particularly long chain ceramide d18:1/20:0 or d18:1/24:0 were elevated, likely contributing to the pro-apoptotic environment observed in pulmonary alveolar proteinosis. Cellular debris lipids like phosphatidylethanolamine or phosphatidylserine were only moderately increased by 4 to 7-fold. The surfactant lipid class phosphatidylcholine expanded 17-fold, lyso- phosphatidylcholine 54-fold, and the surfactant proteins A, B, C 144-, 4- and 17-fold. All these changes did not differ between the various diseases causing pulmonary alveolar proteinosis.
Conclusions: This insight into the alveolar lipidome may provide monitoring tools and may open new therapeutic strategies for pulmonary alveolar proteinosis.