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Diverse gene expression in patients with juvenile spondyloartropathy and clavicular cortical hyperostosis is possibly related to autoinflammatory diseases

Introduction: Juvenile Spondyloarthropathies (jSpA) and clavicular cortical hyperostosis (CCH – variant of chronic recurrent multifocal osteomyelitis) are characterized by dysregulation of the inflammatory processes. Objectives: To identify genes with disease-specific expression patterns of patients diagnosed with jSpA, CCH and healthy controls. Patients and methods: Peripheral blood samples of 11 new-onset, untreated jSpA patients were analyzed for expression patterns using Human Genome U133 PLUS 2.0 GeneChip, Affymetrix, (54675 probes). Among these patients all were HLA “double positive”: 8 B27/B7 (OR 14.82), 2 B27/DRB1 (OR 7.39) and 1 B7/DRB1 (OR 2.61). For comparison, gene expression profiles were obtained from 5 patients with CCH and 4 healthy controls. RT-PCR was used to confirm differential gene expression in patients with obtained gene expression profiles (N=20), and additional 21 jSpA patients, 4 patients with CCH, and 7 healthy controls. Results: Statistical analysis of gene expression patterns in patients with jSpA compared to healthy controls, identified 744 differentially expressed genes at statistical cutoffs fold change 1.5 (p<0.05, max>100). Genes differentially expressed in patients with jSpA were compared to the expression profiles of CCH patients, and the analysis showed overlap in 282 genes. Conclusions: jSpA patients exhibit complex patterns of expression in genes related to inflammatory and defense response, MAP kinase and cell cycle, chromatin modulation and transcription, cell death and apoptosis, and interestingly, gene closely linked to autoinflammatory diseases (NRLP3 and TLR-4). Additionally, profiles of patients with jSpA and CCH showed significant concordance in expression of genes linked to autoinflammatory (TLR-4) and autoimmune diseases (CD24).

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

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