Sarcoidosis activates diverse transcriptional programs in bronchoalveolar lavage cells
Author
Gharib, Sina A.; Malur, Anagha; Huizar, Isham; Barna, Barbara P.; Kavuru, Mani S.; Schnapp, Lynn M.; Thomassen, Mary Jane
Abstract
Background: Sarcoidosis is a multisystem immuno-inflammatory disorder of unknown etiology that most
commonly involves the lungs. We hypothesized that an unbiased approach to identify pathways activated in
bronchoalveolar lavage (BAL) cells can shed light on the pathogenesis of this complex disease.
Methods: We recruited 15 patients with various stages of sarcoidosis and 12 healthy controls. All subjects
underwent bronchoscopy with lavage. For each subject, total RNA was extracted from BAL cells and hybridized to
an Affymetrix U133A microarray. Rigorous statistical methods were applied to identify differential gene expression
between subjects with sarcoidosis vs. controls. To better elucidate pathways differentially activated between these
groups, we integrated network and gene set enrichment analyses of BAL cell transcriptional profiles.
Results: Sarcoidosis patients were either non-smokers or former smokers, all had lung involvement and only two
were on systemic prednisone. Healthy controls were all non-smokers. Comparison of BAL cell gene expression
between sarcoidosis and healthy subjects revealed over 1500 differentially expressed genes. Several previously
described immune mediators, such as interferon gamma, were upregulated in the sarcoidosis subjects. Using an
integrative computational approach we constructed a modular network of over 80 gene sets that were highly
enriched in patients with sarcoidosis. Many of these pathways mapped to inflammatory and immune-related
processes including adaptive immunity, T-cell signaling, graft vs. host disease, interleukin 12, 23 and 17 signaling.
Additionally, we uncovered a close association between the proteasome machinery and adaptive immunity,
highlighting a potentially important and targetable relationship in the pathobiology of sarcoidosis.
Conclusions: BAL cells in sarcoidosis are characterized by enrichment of distinct transcriptional programs involved
in immunity and proteasomal processes. Our findings add to the growing evidence implicating alveolar resident
immune effector cells in the pathogenesis of sarcoidosis and identify specific pathways whose activation may
modulate disease progression
Date
2016-07
Citation:
APA:
Gharib, Sina A., & Malur, Anagha, & Huizar, Isham, & Barna, Barbara P., & Kavuru, Mani S., & Schnapp, Lynn M., & Thomassen, Mary Jane. (July 2016).
Sarcoidosis activates diverse transcriptional programs in bronchoalveolar lavage cells.
,
(),
-
. Retrieved from
http://hdl.handle.net/10342/8008
MLA:
Gharib, Sina A., and Malur, Anagha, and Huizar, Isham, and Barna, Barbara P., and Kavuru, Mani S., and Schnapp, Lynn M., and Thomassen, Mary Jane.
"Sarcoidosis activates diverse transcriptional programs in bronchoalveolar lavage cells". .
. (),
July 2016.
December 10, 2023.
http://hdl.handle.net/10342/8008.
Chicago:
Gharib, Sina A. and Malur, Anagha and Huizar, Isham and Barna, Barbara P. and Kavuru, Mani S. and Schnapp, Lynn M. and Thomassen, Mary Jane,
"Sarcoidosis activates diverse transcriptional programs in bronchoalveolar lavage cells," , no.
(July 2016),
http://hdl.handle.net/10342/8008 (accessed
December 10, 2023).
AMA:
Gharib, Sina A., Malur, Anagha, Huizar, Isham, Barna, Barbara P., Kavuru, Mani S., Schnapp, Lynn M., Thomassen, Mary Jane.
Sarcoidosis activates diverse transcriptional programs in bronchoalveolar lavage cells. .
July 2016;
():
.
http://hdl.handle.net/10342/8008. Accessed
December 10, 2023.
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