| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2775119 | Experimental and Molecular Pathology | 2014 | 7 Pages |
•Sarcoidosis is an immune-mediated granulomatous disease diagnosed histopathologically.•Gene expression by RT-PCR was quantified from Formalin-fixed paraffin embedded tissue.•Specific genes were differentially expressed in sarcoid, suture, and fungal granulomas.•Sarcoidosis granulomas are mediated by prominent NF-κB and STAT-1 cytokine signaling.•FFPE tissue gene quantification is a novel effective diagnostic tool for sarcoidosis.
Sarcoidosis is an immune-mediated multisystem disease characterized by the formation of non-caseating granulomas. The pathogenesis of sarcoidosis is unclear, with proposed infectious or environmental antigens triggering an aberrant immune response in susceptible hosts. Multiple pro-inflammatory signaling pathways have been implicated in mediating macrophage activation and granuloma formation in sarcoidosis, including IFN-γ/STAT-1, IL-6/STAT-3, and NF-κB. It is difficult to distinguish sarcoidosis from other granulomatous diseases or assess disease severity and treatment response with histopathology alone. Therefore, development of improved diagnostic tools is imperative. Herein, we describe an efficient and reliable technique to classify granulomatous disease through selected gene expression and identify novel genes and cytokine pathways contributing to the pathogenesis of sarcoidosis. We quantified the expression of twenty selected mRNAs extracted from formalin-fixed paraffin embedded (FFPE) tissue (n = 38) of normal lung, suture granulomas, sarcoid granulomas, and fungal granulomas. Utilizing quantitative real-time RT-PCR we analyzed the expression of several genes, including IL-6, COX-2, MCP-1, IFN-γ, T-bet, IRF-1, Nox2, IL-33, and eotaxin-1 and revealed differential regulation between suture, sarcoidosis, and fungal granulomas. This is the first study demonstrating that quantification of target gene expression in FFPE tissue biopsies is a potentially effective diagnostic and research tool in sarcoidosis.
