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

Arthritis Res Ther. 2019 Feb 12;21(1):51. doi: 10.1186/s13075-019-1829-7.

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: CD4+ T lymphocytes; Epigenetics; MiRNA; Monocytes; Spondyloarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antirheumatic Agents / pharmacology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cells, Cultured
  • Cohort Studies
  • Female
  • Gene Expression Profiling / methods*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spine / drug effects
  • Spine / metabolism
  • Spine / pathology
  • Spondylarthritis / drug therapy
  • Spondylarthritis / genetics*
  • Spondylarthritis / metabolism

Substances

  • Antirheumatic Agents
  • MicroRNAs