![[ Visit Client Website ]](images/banner.gif)
Objective:
Previous studies have reported a distinct gene expression pattern in the peripheral blood cells of patients with Systemic Sclerosis (SSc) and Systemic Lupus Erythematosus (SLE) compared to healthy controls. The current study compares the gene expression patterns of SSc and SLE with each other.
Methods:
We investigated whole blood (PAXgene) transcriptosomes of 29 patients with SSc (12 anti-topoisomerase, 9 anti-RNA-polymerase, and 8 anti-centromere) and 9 gender, ethnicity, and age matched SLE patients utilizing Illumina Human Ref 8 BeadChips. Differentially expressed genes were ascertained using the Optimal Discovery Procedure (J.D. Storey, Univ of Washington, EDGE). We then utilized differentially expressed genes to develop class predictors using 6 different methods.
Results:
We found at least 32 differentially expressed genes between SLE and SSc at a false discovery rate of <10%. Twelve of these were interferon(IFN)-related genes. Principal components analysis revealed that the 3 of the most significantly differential expressed genes accounted for 56% of the variance between the classes.
Of the different class prediction models tested we found that a Bayesian Compound Covariate model comprised of 13 genes differentiated the SLE from SSc with a specificity of 93%.
Global analysis of 377 known biological pathways revealed 9 pathways were differentially regulated, including 2 IFN, and 1 TGF-β related signaling pathways; in addition, there were 2 differentially regulated pathways involved with epidermal homeostatsis and transformation of epithelial cells to a migratory, fibroblastoid phenotype (EMT and NFκB).
Conclusion:These data show that a limited number of genes reliably distinguished SSc from SLE. Previous data have demonstrated the presence of a distinct IFN-related gene signature in SLE and SSc blood. The current data demonstrate that the magnitude of the IFN signal is more intense in SLE than SSc, suggesting that these 2 disease may represent a spectrum of dysregulated innate immunity mediated by IFN
Previous studies have reported a distinct gene expression pattern in the peripheral blood cells of patients with Systemic Sclerosis (SSc) and Systemic Lupus Erythematosus (SLE) compared to healthy controls. The current study compares the gene expression patterns of SSc and SLE with each other.
Methods:
We investigated whole blood (PAXgene) transcriptosomes of 29 patients with SSc (12 anti-topoisomerase, 9 anti-RNA-polymerase, and 8 anti-centromere) and 9 gender, ethnicity, and age matched SLE patients utilizing Illumina Human Ref 8 BeadChips. Differentially expressed genes were ascertained using the Optimal Discovery Procedure (J.D. Storey, Univ of Washington, EDGE). We then utilized differentially expressed genes to develop class predictors using 6 different methods.
Results:
We found at least 32 differentially expressed genes between SLE and SSc at a false discovery rate of <10%. Twelve of these were interferon(IFN)-related genes. Principal components analysis revealed that the 3 of the most significantly differential expressed genes accounted for 56% of the variance between the classes.
Of the different class prediction models tested we found that a Bayesian Compound Covariate model comprised of 13 genes differentiated the SLE from SSc with a specificity of 93%.
Global analysis of 377 known biological pathways revealed 9 pathways were differentially regulated, including 2 IFN, and 1 TGF-β related signaling pathways; in addition, there were 2 differentially regulated pathways involved with epidermal homeostatsis and transformation of epithelial cells to a migratory, fibroblastoid phenotype (EMT and NFκB).
Conclusion:These data show that a limited number of genes reliably distinguished SSc from SLE. Previous data have demonstrated the presence of a distinct IFN-related gene signature in SLE and SSc blood. The current data demonstrate that the magnitude of the IFN signal is more intense in SLE than SSc, suggesting that these 2 disease may represent a spectrum of dysregulated innate immunity mediated by IFN
S. Assassi, None; M.D. Mayes, None; P. Gourh, None; F.C. Arnett, None; J.D. Reveille, None; C. Poage, None; T. McNearney, None; M. Fischbach, None; F.K. Tan, None.