The circulating cell-free microrna profile in systemic sclerosis is distinct from both healthy controls and Systemic Lupus Erythematosus

S. O. Steen, L. V. Iversen, A. L. Carlsen, M. Burton, C. T. Nielsen, S. Jacobsen, N. H. H. Heegaard

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Objective. To evaluate the expression profile of cell-free circulating microRNA (miRNA) in systemic sclerosis (SSc), healthy controls (HC), and systemic lupus erythematosus (SLE). Methods. Total RNA was purified from plasma and 45 different, mature miRNA were measured using quantitative PCR assays after reverse transcription. Samples (n = 189) were from patients with SSc (n = 120), SLE (n = 29), and from HC (n = 40). Expression data were clustered by principal components analysis, and diagnostically specific miRNA profiles were developed by leave-one-out cross-validation. Diagnostic probability scores were derived from stepwise logistic regression. Results. Thirty-seven miRNA specificities were consistently detected and 26 of these were unaffected by SSc sample age and present in more than two-thirds of SSc samples. SSc cases showed a distinct expression profile with 14/26 miRNA significantly decreased (false discovery rate <0.05) and 5/26 increased compared with HC. A 21-miRNA classifier gave optimum accuracy (80%) for discriminating SSc from both HC and SLE. The discrimination between HC and SSc (95% accuracy) was strongly driven by miRNA of the 17-92 cluster and by miR-16, -223, and -638, while SLE and SSc differed mainly in the expression of miR-142-3p, -150, -223, and -638. Except for a weak correlation between anti-Scl-70 and miR-638 (p = 0.048), there were no correlations with other patient variables. Conclusion. Circulating miRNA profiles are characteristic for SSc compared with both HC and SLE cases. Some of the predicted targets of the differentially regulated miRNA are of relevance for transforming growth factor-beta signaling and fibrosis, but need to be validated in independent studies. (First Release Nov 15 2014; J Rheumatol 2015;42:214-21; doi:10.3899/jrheum.140502).
Original languageEnglish
JournalJournal of Rheumatology
Volume42
Issue number2
Pages (from-to)214-21
ISSN0315-162X
DOIs
Publication statusPublished - Feb 2015

Keywords

  • Classification
  • Diagnosis
  • MicroRNA
  • Systemic lupus erythematosus
  • Systemic sclerosis
  • Scleroderma, Systemic/blood
  • Diagnosis, Differential
  • Cross-Sectional Studies
  • Humans
  • Middle Aged
  • Male
  • Young Adult
  • MicroRNAs/blood
  • Adult
  • Biomarkers/blood
  • Female
  • Aged
  • Lupus Erythematosus, Systemic/blood

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