D23-04 Lipidome Profile of Serum Reveals Distinctive Lipidomic Characteristics in Pulmonary Alveolar Proteinosis: A Targeted Liquid Chromatography-Mass Spectrometry Approach

Rationale Pulmonary alveolar proteinosis (PAP) is a rare respiratory disease whose pathogenesis is characterized by impaired GM-CSF signaling in alveolar macrophages, resulting in dysregulated cholesterol efflux. Although prior investigations have identified abnormalities in lipid metabolism in both bronchoalveolar lavage fluid and serum from PAP patients, the specific features of serum lipid metabolism remain incompletely defined. Methods We performed a targeted lipidomics analysis including 65 patients with PAP and 65 age- and sex-matched healthy controls. Serum samples were collected at baseline; follow-up samples were also obtained from patients who achieved disease remission after treatment. A total of 21 lipid subclasses were quantified using targeted liquid chromatography-mass spectrometry. Results We quantified 792 lipid species, among which 15 subclasses showed significantly altered concentrations (P < 0.05). Orthogonal partial least squares-discriminant analysis (OPLS-DA) was applied to identify differentially abundant metabolites, leading to the selection of 333 lipids (FDR < 0.05, VIP > 1). A multivariate ROC analysis based on a support vector machine combined with recursive feature elimination yielded a 6-lipid biomarker panel, comprising LPG 18:0, LPG 16:0, FA 20:3, FA 22:6, DG 16:0/20:4, and FA 22:3, which achieved an accuracy of 0.941 and an area under the curve (AUC) of 0.957. Correlation analyses revealed associations between clinical parameters and lipid levels: LPG 16:0, LPG 18:0, and LPI 16:0 correlated positively with the alveolar-arterial oxygen gradient (A-aDO2; r = 0.549, P < 0.001), whereas HexCer 18:1/16:0 was inversely associated with diffusing capacity of the lung for carbon monoxide (DLCO; r = −0.455, P < 0.001). Furthermore, 32 lipids, including species from CE, TG, LPE, FA, SM, and LPG subclasses, were significantly decreased following disease remission (P < 0.005). Conclusions Serum lipidomic profiling reveals distinct alterations in patients with pulmonary alveolar proteinosis. A 6-lipid biomarker panel demonstrates a high diagnostic performance for PAP and may serve as a potential diagnostic tool. Lipids associated with disease remission could inform therapeutic response and lead to further investigation on metabolic pathways involved in the disease pathogenesis.