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Abstract Number: 659

Circulating Cell-free microRNAs in Systemic Sclerosis

Samantha Steen1, Anting L. Carlsen2, Line V. Iversen1, Christoffer T. Nielsen3, Christian Lood4, Anders A. Bengtsson4 and Niels H. H. Heegaard1, 1Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen, Denmark, 2Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen, Denmark, 3Infectious Diseases and Rheumatology, University Hospital Rigshospitalet, Copenhagen, Denmark, 4Department of Clinical Sciences, Section of Rheumatology, Lund University, Lund, Sweden

Meeting: ACR/ARHP Annual Meeting 2013

Keywords: MicroRNA and systemic sclerosis

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Session Information

Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's I

Session Type: Abstract Submissions (ACR)

Background/Purpose: microRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression through target mRNAs and are involved in important physiological and pathological processes. Alterations in miRNA expression have been reported in autoimmune diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis, and in fibrotic disorders such as idiopathic pulmonary fibrosis. Systemic sclerosis (SSc) is characterized by fibrosis, vasculopathy and immunological disturbances, and the differential diagnosis and assessment of SSc disease activity can be challenging. The aim of this study was to identify putative circulating miRNAs in SSc patients as biomarkers for diagnosis, disease complications, and activity.

Methods: Total RNA was purified from platelet-poor plasma from 121 SSc patients, 29 SLE patients and 40 healthy controls, and the expression of 45 different specific miRNAs was determined using a quantitative real-time PCR dynamic array. Expression data and diagnosis and clinical parameters were analyzed for correlations.

Results: Twenty-seven miRNAs were significantly differentially expressed in SSc patients compared with healthy controls (p < 0.05). Nineteen miRNAs were down-regulated in SSc (miR-16, -17, -20a, -21, -24, -27a-3p, -29c-3p, -92a, -106a, -142-3p, -145-5p, -146b, -184, -192-5p, -221, -223, -342-3p, -375 and -423-5p), whereas 8 miRNAs were up-regulated in SSc (-29a, -29b-3p, -150, -181b, -203, -409-3p, -590-5p and -638). Ten miRNAs were found to be statistically differentially expressed in SSc patients compared with both healthy controls and SLE patients (p < 0.05). Receiver operating characteristic (ROC) analysis underlined the potential use of 4 miRNAs as biomarkers in SSc diagnostics, and revealed a promising 2 miRNA model to discriminate SSc patients from healthy controls when combining miR-106a with miR-181b (AUC = 0.91).

Conclusion: The expression of cell-free circulating miRNAs is altered in SSc compared with healthy controls and SLE patients. A promising 2 miRNA index differentiates SSc patients from healthy controls.


Disclosure:

S. Steen,
None;

A. L. Carlsen,
None;

L. V. Iversen,
None;

C. T. Nielsen,
None;

C. Lood,
None;

A. A. Bengtsson,
None;

N. H. H. Heegaard,
None.

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