engleski

Distinctive gene expression in patients with juvenile spondyloartropathy is related to autoinflammatory diseases

Introduction: Juvenile Spondyloarthropathies (jSpA) are characterized by dysregulation of the inflammatory processes and bone metabolism which may be clarified by gene expression profiles. Objectives: To identify genes with disease-specific expression patterns of patients diagnosed with jSpA and healthy controls using microarray-based methods. Methodology: Peripheral blood samples of 6 HLA-B27/B7 „double positive“ patients (OR=14.9) with new onset, untreated disease were analyzed for expression patterns that correlated with disease characteristics using Human Genome U133 PLUS 2.0 GeneChip, Affymetrix, (6x106 SNP’s). For comparison, gene expression profiles were obtained from 4 healthy controls. Real-time PCR was used for confirmation of gene expression differences. Results: Statistical analysis of gene expression patterns identified 369 differentially expressed genes at statistical cutoffs fold change 1.5(p<0.05, max>100). There were also 163 mRNAs with significantly increased expression, and 197 mRNAs with significantly decreased expression. The genes represented by these probe sets were enriched for functions related to inflammatory modulation, MAP kinase pathway, TGFbeta family, as well as other enzymes and receptors (myosin light chain kinase, NRLP3 (inflammasome), thrombomodulin, protein-tyrosin phospahase, receptor type 2 (PTPRN2), TRAF1, and ZAP-70. Using network, DAVID, and GSEA analysis we discovered gene hubs among the differentially expressed genes based on correlation of expression (T-cell regulation, energy metabolism, RNA processing). Conclusions: This study demonstrates that jSpA patients exhibit complex patterns of gene expression for functions related to inflammatory and defense response, MAP kinase and cell cycle, chromatin modulation and transcription, cell death, apoptosis, and interestingly, gene closely linked to autoinflmmatory diseases (NRLP3).

juvenile spondyloarthropathies ; jSpA ; microarray ; Clavicular cortical hyperostosis ; CCH

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