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• W2071497666 abstract "Abstract Objective To determine whether macrophages, a type of cell implicated in the pathogenesis of ankylosing spondylitis (AS), exhibit a characteristic gene expression pattern. Methods Macrophages were derived from the peripheral blood of 8 AS patients (median disease duration 13 years [range <1–43 years]) and 9 healthy control subjects over 7 days with the use of granulocyte–macrophage colony‐stimulating factor. Cells were stimulated for 24 hours with interferon‐γ (IFNγ; 100 units/ml), were left untreated for 24 hours, or were treated for 3 hours with lipopolysaccharide (LPS; 10 ng/ml). RNA was isolated and examined by microarray and real‐time quantitative reverse transcription–polymerase chain reaction analysis. Results Microarray analysis revealed 198 probe sets detecting the differential expression of 141 unique genes in untreated macrophages from AS patients compared with healthy controls. Clustering and principal components analysis clearly distinguished AS patients and controls. Of the differentially expressed genes, 78 (55%) were IFN‐regulated, and their relative expression indicated a “reverse” IFN signature in AS patient macrophages, where IFNγ–up‐regulated genes were underexpressed and down‐regulated genes were overexpressed. Treatment of macrophages with exogenous IFNγ normalized the expression of these genes between patients and controls. In addition, the messenger RNA encoded by the IFNγ gene was ∼2‐fold lower in AS patient macrophages at baseline ( P = 0.004) and was poorly responsive to LPS ( P = 0.018), as compared with healthy controls. Conclusions Our findings reveal consistent differences in gene expression in macrophages from AS patients, with evidence of a striking “reverse” IFN signature. Together with poor expression and responsiveness of the IFNγ gene, these results suggest that there may be a relative defect in IFNγ gene regulation, with autocrine consequences and implications for disease pathogenesis." @default.
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• W2071497666 date "2008-05-31" @default.
• W2071497666 modified "2023-10-18" @default.
• W2071497666 title "Gene expression analysis of macrophages derived from ankylosing spondylitis patients reveals interferon-γ dysregulation" @default.
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• W2071497666 doi "https://doi.org/10.1002/art.23512" @default.
• W2071497666 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2888278" @default.
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