ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2276

Signature of Circulating Micro-RNA in Systemic Lupus Erythematosus

Anting L. Carlsen1, Aaron J. Schetter2, Christoffer T. Nielsen3, Christian Lood4, Steen Knudsen5, Anne Voss6, Curtis C. Harris7, Thomas Hellmark8, Mårten Segelmark9, Søren Jacobsen10, Anders A. Bengtsson4 and Niels H. H. Heegaard11, 1Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen, Denmark, 2National Cancer Institute, National Institutes of Health, Bethesda, MD, 3Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen S, Denmark, 4Department of Clinical Sciences, Section of Rheumatology, Lund University, Lund, Sweden, 5Medical Prognosis Institute, Horsholm, Denmark, 6Dept of Rheumatology, Odense University Hospital, Odense C, Denmark, 7Laboratory of Human Carcinogenesis, National Cancer Institute NIH, Bethesda, MD, 8Nephrology, Department of Clinical Sciences, Lund University, Lund, Sweden, 9Nephrology, Linkobing University, Linkoping University, Linkoping, Sweden, 10Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, 11Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen, Denmark

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by chronic inflammation sustained by a type I interferon response. The diagnostic value of circulating micro-RNA (miRNA) signatures in SLE has not been systematically evaluated and compared to healthy controls and other autoimmune conditions.

Methods: We quantified 45 mature miRNAs in 409 plasma samples from clinically well-characterized SLE patients, healthy controls, and controls with other systemic autoimmune diseases (RA and vasculitis) and immunosuppressed patients (kidney transplant recipients). SLE risk probability scores were modeled by logistic regression and validated in independent cohorts.

Results: Highly significant changes in 7 specific miRNAs were identified and validated independently. Up-regulated miRNAs were miR-142-3p and -181a and down-regulated miRNAs were miR-106a, -17, -20a, -92a, and -203. Four of five down-regulated miRNAs represent members of the polycistronic miR-17-92 family and, together with miR-223, were significantly lower in SLE patients with active nephritis than in patients without nephritis. A predictive model for the SLE diagnosis based on 2 miRNAs discriminated SLE from controls (AUC=0.89) when validated independently (accuracy: 76%, p<2x10-9). Using a 4 miRNA model SLE cases was grouped statistically significantly different from disease controls except for vasculitis samples.

Conclusion: We find consistent changes of circulating miRNA profiles in SLE patients compared with healthy controls and disease controls. All 7 validated differently expressed miRNAs target genes in the TGF-b signaling pathway. Other targets imply regulation of apoptosis, cytokine-cytokine receptors, T-cell development, and cytoskeletal organization. A four-miRNA signature was diagnostic for SLE, and patients with active nephritis showed specific subset miRNA profiles. The findings highlight possible deregulated pathways in SLE and suggest that circulating miRNA signatures may potentially be used diagnostically and for monitoring purposes in SLE.

Disclosure:

A. L. Carlsen,
None;

A. J. Schetter,
None;

C. T. Nielsen,
None;

C. Lood,
None;

S. Knudsen,
None;

A. Voss,
None;

C. C. Harris,
None;

T. Hellmark,
None;

M. Segelmark,
None;

S. Jacobsen,
None;

A. A. Bengtsson,
None;

N. H. H. Heegaard,
None.

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