Hypothesis: Sarcoidosis is a STAT1-mediated disease

Immunologic pathways involved in sarcoidosis pathogenesis are largely unknown. We hypothesized that patients with sarcoidosis have characteristic mRNA profiles. Microarray analysis of gene expression was done on peripheral blood (12 patients, 12 controls), lung (6 patients, 6 controls) and lymph nod...

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Published in:Clinical immunology (Orlando, Fla.) Vol. 132; no. 2; pp. 174 - 183
Main Authors: Rosenbaum, James T., Pasadhika, Sirichai, Crouser, Elliott D., Choi, Dongseok, Harrington, Christina A., Lewis, Jinnell A., Austin, Carrie R., Diebel, Tessa N., Vance, Emily E., Braziel, Rita M., Smith, Justine R., Planck, Stephen R.
Format: Journal Article
Language:English
Published: Amsterdam Elsevier Inc 01.08.2009
Elsevier
Subjects:
Adult
Aged
Allergy and Immunology
Biological and medical sciences
Down-Regulation
Female
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Gene Expression Profiling
Gene Regulatory Networks
Genetic Predisposition to Disease - genetics
Humans
Lung - metabolism
Lymph Nodes - metabolism
Male
Medical sciences
Microarray analysis
Middle Aged
Models, Genetic
Oligonucleotide Array Sequence Analysis - methods
Ophthalmology
Phosphoproteins - genetics
Receptors, Interferon - genetics
Sarcoidosis
Sarcoidosis - genetics
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
STAT1 Transcription Factor - genetics
Up-Regulation
Uvea diseases
Uveitis
Young Adult
Sarcoidosis
Gene expression profiling
Uveitis
Microarray analysis
Transcription factor STAT1
Eye disease
Immunology
Systemic disease
Uvea disease
Hypothesis
Gene expression profile
ISSN:1521-6616, 1521-7035, 1521-7035
Online Access:Get full text
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Summary:Immunologic pathways involved in sarcoidosis pathogenesis are largely unknown. We hypothesized that patients with sarcoidosis have characteristic mRNA profiles. Microarray analysis of gene expression was done on peripheral blood (12 patients, 12 controls), lung (6 patients, 6 controls) and lymph node (8 patients, 5 controls). Comparing peripheral blood from patients with sarcoidosis to controls, 872 transcripts were upregulated and 1039 were downregulated at > 1.5-fold change and a significant q value. Several transcripts associated with interferon and STAT1 were upregulated. Lung and lymph node analyses also showed dramatic increases in STAT1 and STAT1-regulated chemokines. Granulomas in lymph nodes of patients with sarcoidosis expressed abundant STAT1 and phosphorylated STAT1. STAT1 might play an important role in sarcoidosis. This novel hypothesis unites seemingly disparate observations with regard to sarcoidosis including implication of a casual role for interferons, a suspected infectious trigger, T H1 predominating lymphocytes in bronchoalveolar lavage, and the association with hypercalcemia.
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ISSN:1521-6616
1521-7035
1521-7035
DOI:10.1016/j.clim.2009.04.010