Pulmonary involvement occurs in up to 95% of sarcoidosis cases. In this pilot study, we examine lung compartment-specific protein expression to identify pathways linked to development and progression of pulmonary sarcoidosis. We characterized bronchoalveolar lavage (BAL) cells and fluid (BALF) proteins in recently diagnosed sarcoidosis cases. We identified 4,306 proteins in BAL cells, of which 272 proteins were differentially expressed in sarcoidosis compared to controls. These proteins map to novel pathways such as integrin-linked kinase and IL-8 signaling and previously implicated pathways in sarcoidosis, including phagosome maturation, clathrin-mediated endocytic signaling and redox balance. In the BALF, the differentially expressed proteins map to several pathways identified in the BAL cells. The differentially expressed BALF proteins also map to aryl hydrocarbon signaling, communication between innate and adaptive immune response, integrin, PTEN and phospholipase C signaling, serotonin and tryptophan metabolism, autophagy, and B cell receptor signaling. Additional pathways that were different between progressive and non-progressive sarcoidosis in the BALF included CD28 signaling and PFKFB4 signaling. Our studies demonstrate the power of contemporary proteomics to reveal novel mechanisms operational in sarcoidosis. Application of our workflows in well-phenotyped large cohorts maybe beneficial to identify biomarkers for diagnosis and prognosis and therapeutically tenable molecular mechanisms.
Bibliographical noteFunding Information:
The authors greatly appreciate the patients and the research participants. They also thank the personnel at the Center for Mass Spectrometry and Proteomics, especially LeeAnn Higgins and Todd Markowski for MS analysis. The Minnesota Supercomputing Institute maintains GalaxyP at the University of Minnesota, and the infrastructure is supported by National Cancer Institute Grant U24CA199347 (TJG). Lee S Parsons PhD assisted in implementing Maxquant on Mesabi servers at Minnesota Supercomputing Institute. The project was supported by the University of Minnesota Department of Medicine and the Division of Pulmonary and Critical Care (MB), Sarcoidosis Research and Education Foundation (MB), R01ES023826 (LAM. LL), R01HL140357 (LAM), U01 HL112695 and UL1TR002535 (LAM)
© 2020, The Author(s).
Copyright 2020 Elsevier B.V., All rights reserved.
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't