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PLoS By Category | Recent PLoS Articles
Pathology - Public Health and Epidemiology - Respiratory Medicine

Peripheral Blood Gene Expression as a Novel Genomic Biomarker in Complicated Sarcoidosis
Published: Wednesday, September 12, 2012
Author: Tong Zhou et al.

by Tong Zhou, Wei Zhang, Nadera J. Sweiss, Edward S. Chen, David R. Moller, Kenneth S. Knox, Shwu-Fan Ma, Michael S. Wade, Imre Noth, Roberto F. Machado, Joe G. N. Garcia

Sarcoidosis, a systemic granulomatous syndrome invariably affecting the lung, typically spontaneously remits but in ~20% of cases progresses with severe lung dysfunction or cardiac and neurologic involvement (complicated sarcoidosis). Unfortunately, current biomarkers fail to distinguish patients with remitting (uncomplicated) sarcoidosis from other fibrotic lung disorders, and fail to identify individuals at risk for complicated sarcoidosis. We utilized genome-wide peripheral blood gene expression analysis to identify a 20-gene sarcoidosis biomarker signature distinguishing sarcoidosis (n?=?39) from healthy controls (n?=?35, 86% classification accuracy) and which served as a molecular signature for complicated sarcoidosis (n?=?17). As aberrancies in T cell receptor (TCR) signaling, JAK-STAT (JS) signaling, and cytokine-cytokine receptor (CCR) signaling are implicated in sarcoidosis pathogenesis, a 31-gene signature comprised of T cell signaling pathway genes associated with sarcoidosis (TCR/JS/CCR) was compared to the unbiased 20-gene biomarker signature but proved inferior in prediction accuracy in distinguishing complicated from uncomplicated sarcoidosis. Additional validation strategies included significant association of single nucleotide polymorphisms (SNPs) in signature genes with sarcoidosis susceptibility and severity (unbiased signature genes - CX3CR1, FKBP1A, NOG, RBM12B, SENS3, TSHZ2; T cell/JAK-STAT pathway genes such as AKT3, CBLB, DLG1, IFNG, IL2RA, IL7R, ITK, JUN, MALT1, NFATC2, PLCG1, SPRED1). In summary, this validated peripheral blood molecular gene signature appears to be a valuable biomarker in identifying cases with sarcoidoisis and predicting risk for complicated sarcoidosis.
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