Abstract
A subset of beryllium-exposed workers develop beryllium sensitisation (BeS) which precedes chronic beryllium disease (CBD). We conducted an in-depth analysis of differentially expressed candidate genes in CBD.
We performed Affymetrix GeneChip 1.0 ST array analysis on peripheral blood mononuclear cells (PBMCs) from 10 CBD, 10 BeS and 10 beryllium-exposed, nondiseased controls stimulated with BeSO4 or medium. The differentially expressed genes were validated by high-throughput real-time PCR in this group and in an additional group of cases and nonexposed controls. The functional roles of the top candidate genes in CBD were assessed using a pharmacological inhibitor. CBD gene expression data were compared with whole blood and lung tissue in sarcoidosis from the Gene Expression Omnibus.
We confirmed almost 450 genes that were significantly differentially expressed between CBD and controls. The top enrichment of genes was for JAK (Janus kinase)–STAT (signal transducer and activator of transcription) signalling. A JAK2 inhibitor significantly decreased tumour necrosis factor-α and interferon-γ production. Furthermore, we found 287 differentially expressed genes overlapped in CBD/sarcoidosis. The top shared pathways included cytokine–cytokine receptor interactions, and Toll-like receptor, chemokine and JAK–STAT signalling pathways.
We show that PBMCs demonstrate differentially expressed gene profiles relevant to the immunnopathogenesis of CBD. CBD and sarcoidosis share similar differential expression of pathogenic genes and pathways.
Abstract
Chronic beryllium disease and sarcoidosis share similar differential expression of pathogenic genes and pathways http://ow.ly/YgjIA
Footnotes
Editorial comment in Eur Respir J 2016; 47: 1625–1628.
This article has supplementary material available from erj.ersjournals.com
Support statement: Supported by NIH P01 ES11810-06A1, K12 HL090147-01, K01 ES020857-01 and 1 UL1 TR001082 from NCRR/NIH. Funding information for this article has been deposited with FundRef.
Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com
- Received September 29, 2015.
- Accepted February 7, 2016.
- Copyright ©ERS 2016