Global microRNA profiling of peripheral blood mononuclear cells in patients with Behçet's disease.
OBJECTIVE
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-polymerase 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.
Cattedra e Unità di Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Università e AOU di Sassari, Italy. e.gianluca@libero.it.
Gian Luca
GL
Erre
Cattedra e Unità di Reumatologia, Dipartimento di Scienze Mediche, Università e AOU di Cagliari, Monserrato, Italy.
Matteo
M
Piga
Dipartimento di Scienze Biomediche, Università di Sassari, Italy.
Ciriaco
C
Carru
Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Monserrato; and CRS4, Parco Tecnologico della Sardegna, Pula, Italy.
Andrea
A
Angius
Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Monserrato, Italy.
Laura
L
Carcangiu
Cattedra e Unità di Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Università e AOU di Sassari, Italy.
Marco
M
Piras
Dipartimento di Scienze Biomediche, Università di Sassari, Italy.
Salvatore
S
Sotgia
Dipartimento di Scienze Biomediche, Università di Sassari, Italy.
Angelo
A
Zinellu
Cattedra e Unità di Reumatologia, Dipartimento di Scienze Mediche, Università e AOU di Cagliari, Monserrato, Italy.
Alessandro
A
Mathieu
Cattedra e Unità di Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Università e AOU di Sassari, Italy.
Giuseppe
G
Passiu
Health e-solutions, Rotterdam, The Netherlands.
Mario
M
Pescatori
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001528:Behcet Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry*; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011237:Predictive Value of Tests; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D055815:Young Adult
D005819:Genetic Markers; C568636:MIRN720 microRNA, human; D035683:MicroRNAs; C531408:mirn199 microRNA, human