Novel Protein Pathways in Development and Progression of Pulmonary Sarcoidosis.

Sarcoidosis is a disease that affects multiple organ systems, with lung disease seen commonly and is the most frequent cause of sarcoidosis-related mortality. We investigated to compare protein expression in the lung from both bronchoalveolar lavage fluid (BAL) cells and fluid (BALF) in newly diagnosed patients with sarcoidosis. Mass spectral data acquisition was conducted on an Orbitrap Fusion instrument in data-dependent mode using either label-free (BALF) or label-based (intracellular) approach. We identified 4,306 high confidence intracellular proteins (probability >99%) with 272 differentially expressed proteins controlling for an FDR 5%. The protein map to several known canonical pathways including phagosome maturation, clathrin-mediated endocytic signaling, NRF-2 mediated oxidant stress response, The examination of BALF identified 1,192 proteins, xxx and xxx protein with differential expression between controls vs. sarcoidosis and progressive vs. non-progressive sarcoidosis respectively. Several of the proteins identified mapping to the differentially expressed proteins were also detected in the BALF.