Deregulation of microRNA expression in monocytes and CD4+ T lymphocytes from patients with axial spondyloarthritis

Abstract

Abstract Background MicroRNAs (MiRs) play an important role in the pathogenesis of chronic inflammatory diseases. This study is the first to investigate miR expression profiles in purified CD4+ T lymphocytes and CD14+ monocytes from patients with axial spondyloarthritis (axSpA) using a high-throughput qPCR approach. Methods A total of 81 axSpA patients fulfilling the 2009 ASAS classification criteria, and 55 controls were recruited from October 2014 to July 2017. CD14+ monocytes and CD4+ T lymphocytes were isolated from peripheral blood mononuclear cells. MiR expression was investigated by qPCR using the Exiqon Human MiRnome panel I analyzing 372 miRNAs. Differentially expressed miRNAs identified in the discovery cohort were validated in the replication cohort. Results We found a major difference in miR expression patterns between T lymphocytes and monocytes regardless of the patient or control status. Comparing disease-specific differentially expressed miRs, 13 miRs were found consistently deregulated in CD14+ cells in both cohorts with miR-361-3p, miR-223-3p, miR-484, and miR-16-5p being the most differentially expressed. In CD4+ T cells, 11 miRs were differentially expressed between patients and controls with miR-16-1-3p, miR-28-5p, miR-199a-5p, and miR-126-3p were the most strongly upregulated miRs among patients. These miRs are involved in disease relevant pathways such as inflammation, intestinal permeability or bone formation. Mir-146a-5p levels correlated inversely with the degree of inflammation in axSpA patients. Conclusions We demonstrate a consistent deregulation of miRs in both monocytes and CD4+ T cells from axSpA patients, which could contribute to the pathophysiology of the disease with potential interest from a therapeutic perspective.

Keywords

• Spondyloarthritis
• MiRNA
• Epigenetics
• CD4+ T lymphocytes
• Monocytes