Circulating miR-99b-5p as a novel predictor of erosion progression on high-resolution peripheral quantitative computed tomography in early rheumatoid arthritis: A prospective cohort study

Int J Rheum Dis. 2019 Sep;22(9):1724-1733. doi: 10.1111/1756-185X.13644. Epub 2019 Jul 4.

Abstract

Objectives: To compare micro RNA (miRNA) expression: (a) between healthy individuals and early rheumatoid arthritis (ERA) patients with and without erosion on high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline; and (b) to explore whether these miRNAs could inform a signature predictive of erosion progression despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

Methods: The second metacarpophalangeal head (MCP2) was scanned by HR-pQCT at baseline and 1 year in 117 ERA patients. We performed global profiling of 377 miRNAs in 10 ERA patients with and without erosion on HR-pQCT at baseline and six healthy controls. Validation of the miRNAs of interest were conducted using TaqMan® quantitative real-time polymerase chain reaction in the validation ERA cohort (n = 117) at baseline. Correlation between the candidate miRNAs and erosion progression over 1 year were also assessed.

Results: In the 377 screened miRNAs, 94 (60.6%) miRNAs were upregulated in patients with erosions, with 13 (8.4%) upregulated more than 2-fold. Sixty-one (39.4%) miRNAs were downregulated in patients with erosions, with 6 (3.9%) downregulated more than 2-fold. Expression of miR-143-3p, miR-145-5p and miR-99b-5p were significantly higher in the plasma of ERA patients with erosions compared with those without erosions. Logistic regression analysis revealed that the baseline expression of miR-99b-5p was an independent predictor of erosion progression at month 12 (Exp [B] = 4.257, 95% CI 1.178-15.386, P = 0.027).

Conclusions: Differential expressions of circulating miR-143-3p, miR-145-5p and miR-99b-5p in the plasma of ERA patients may characterize a severe form of the disease. MiR-99b-5p, in particular, may serve as a possible predictor for erosion progression.

Keywords: HR-pQCT; early rheumatoid arthritis; erosion progression; miRNAs.

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / diagnostic imaging*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / genetics
  • Case-Control Studies
  • Circulating MicroRNA / blood*
  • Circulating MicroRNA / genetics
  • Disease Progression
  • Early Diagnosis
  • Female
  • Genetic Markers
  • Humans
  • Male
  • Metacarpophalangeal Joint / diagnostic imaging*
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Reproducibility of Results
  • Risk Factors
  • Severity of Illness Index
  • Time Factors
  • Tomography, X-Ray Computed*
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • Circulating MicroRNA
  • Genetic Markers
  • MIRN99 microRNA, human
  • MicroRNAs