Changes in MiRNA-5196 Expression as a Potential Biomarker of Anti-TNF-α Therapy in Rheumatoid Arthritis and Ankylosing Spondylitis Patients

Arch Immunol Ther Exp (Warsz). 2018 Oct;66(5):389-397. doi: 10.1007/s00005-018-0513-y. Epub 2018 May 9.

Abstract

In this study, we analysed the expression level of sera circulating miRNA-5196 in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients before and after tumor necrosis factor (TNF)-α therapy as biomarkers predicting positive treatment outcome. We enrolled 10 RA patients, 13 AS patients, and 12 healthy individuals in the study. The expression of miRNA-5196 was measured by real-time polymerase chain reaction before and after anti-TNF-α therapy. Disease activity of RA patients was assessed using disease activity score 28 (DAS28), whereas ankylosing spondylitis DAS (ASDAS) was used in AS patients. MiRNA-5196 expression was significantly higher in patients with RA and AS before TNF-α therapy than in those following anti-TNF-α therapy and healthy controls. Changes in miRNA-5196 expression positively correlated with delta DAS28 or delta ASDAS, respectively, following TNF-α therapy. In contrast, changes in C-reactive protein (CRP) levels in RA and AS patients did not positively correlate with DAS28 or ASDAS changes. Receiver-operating characteristic analysis showed better diagnostic accuracy of miRNA-5196 expression both in RA (area under curve (AUC) = 0.87, p = 0.055) and AS patients (AUC = 0.90, p = 0.050) compared to CRP levels in RA (AUC = 0.75, p = 0.201) and AS patients (AUC = 0.85, p = 0.086) upon biologic therapy treatment. Finding novel biomarkers, including miRNA-5196 which allow to predict and monitor anti-TNF-α response, would be of clinical value especially during the early phase of RA or AS development.

Keywords: Ankylosing spondylitis; Anti-TNF-α; Biologic therapy; Biomarker; MiRNA; Rheumatoid arthritis.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Female
  • Gene Expression Regulation / drug effects*
  • Humans
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • Real-Time Polymerase Chain Reaction
  • Spondylitis, Ankylosing / blood
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / genetics
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Biomarkers
  • MIRN5196 microRNA, human
  • MicroRNAs
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein