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Global microRNA profiling of peripheral blood mononuclear cells in patients with Behçet's disease.

1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11

  1. Cattedra e Unità di Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Università e AOU di Sassari, Italy. e.gianluca@libero.it
  2. Cattedra e Unità di Reumatologia, Dipartimento di Scienze Mediche, Università e AOU di Cagliari, Monserrato, Italy.
  3. Dipartimento di Scienze Biomediche, Università di Sassari, Italy.
  4. Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Monserrato; and CRS4, Parco Tecnologico della Sardegna, Pula, Italy.
  5. Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Monserrato, Italy.
  6. Cattedra e Unità di Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Università e AOU di Sassari, Italy.
  7. Dipartimento di Scienze Biomediche, Università di Sassari, Italy.
  8. Dipartimento di Scienze Biomediche, Università di Sassari, Italy.
  9. Cattedra e Unità di Reumatologia, Dipartimento di Scienze Mediche, Università e AOU di Cagliari, Monserrato, Italy.
  10. Cattedra e Unità di Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Università e AOU di Sassari, Italy.
  11. Health e-solutions, Rotterdam, The Netherlands.

CER8059 Submission on line
2015 Vol.33, N°6 ,Suppl.94 - PI 0072, PF 0079
Full Papers

Rheumatology Article

 

Abstract

OBJECTIVES:
To explore the post-transcriptional regulation of the peripheral blood mononuclear cells (PBMCs) transcriptome by microRNAs in Behçet’s disease (BD).
METHODS:
Using TaqMan Low Density Array-based microRNAs expression profiling, the expression of 750 mature human microRNAs in PBMCs from 5 BD patients and 3 healthy controls (HC) was compared. The expression of deregulated microRNAs was then validated by quantitative real time-poly-merase chain reaction (qRT-PCR), in 42 BD patients and 8 HC.
RESULTS:
In the initial screening, 13 microRNAs appeared deregulated in BD vs HC. Among them, the differential expression of miR-720 and miR-139-3p was confirmed by qRT-PCR, (p<0.05 and FDR <5%). Areas under the receiver operating characteristic curve for miR-139-3p, miR-720 and miR-139-3p + miR-720 in the validation cohort were 0.84, 0.87 and 0.92 respectively, indicating good discrimination between BD patients and HC. Post-hoc analysis showed that 9 out of 13 microRNAs from the discovery phase were significantly upregulated in active vs. quiescent BD, suggesting inflammation as a key regulator of microRNAs machinery in BD. In silico analysis revealed that several BD candidate susceptibility genes are predicted target of significantly deregulated microRNAs in active BD. A significant enrichment in microRNAs targeting elements of the Toll-like receptor (TLR) and T-cell receptor signalling pathways was also assumed.
CONCLUSIONS:
miR199-3p and miR720 deserve further confirmation as biomarkers of BD in larger studies. PBMCs from active BD displayed a unique signature of microRNAs which may be implicated in regulation of innate immunity activation and T-cell function.

PMID: 26486198 [PubMed]

Received: 25/10/2014 - Accepted : 27/05/2015 - In Press: 19/10/2015 - Published: 04/11/2015