title: Specific autoantibody profiles and disease subgroups correlate with circulating micro-RNA in systemic sclerosis.
abstract: OBJECTIVE
  To evaluate the expression profiles of cell-free plasma miRNAs in SSc and to characterize their correlation with disease subgroups (lcSSc and dcSSc) and with autoantibody profiles.
  
  
  METHODS
  Using quantitative RT-PCR, the abundance of 45 mature miRNAs in plasma was determined in 95 patients (lcSSc = 63; dcSSc = 32), representing the following autoantibody subgroups: ACA, anti-DNA topoisomerase I, anti-RNA polymerase III and anti-U1-ribonucleoprotein. MiRNA data were correlated with clinical and paraclinical data. Multiple regression was used to model membership of the lcSSc, dcSSc and autoantibody subgroups, based on miRNA expression profiles.
  
  
  RESULTS
  Thirty-six miRNAs were measurable in all samples. Four (miRNA-223, -181b, -342-3p and -184) were differently expressed in lcSSc and dcSSc (false discovery rate < 0.05). Ten miRNAs exhibited statistically significantly different levels in one or more autoantibody groups, and five (miRNA-409, -184, -92a, -29a and -101) remained significant after correction for multiple comparisons. Multiple regression models accurately predicted ACA and anti-DNA topoisomerase I antibody-positive patients (area under the curve (AUC) = 0.97 and 0.93, respectively) as well as membership of the dcSSc and lcSSc groups (AUC = 0.88).
  
  
  CONCLUSIONS
  Circulating miRNA profiles differ between lcSSc and dcSSc patients and between patients with different autoantibodies. This is the first time autoantibody profiles, disease phenotypes and plasma miRNA profiles have been shown to correlate in an autoimmune disease. The data support a pathobiological role of miRNAs because specific miRNAs associate with autoantibody profiles of known diagnostic and prognostic value.
authors.affiliation: Section of Rheumatology, Department of Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden, dirk.wuttge@med.lu.se.
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Wuttge
authors.affiliation: Department of Autoimmunology & Biomarkers, Statens Serum Institut, Copenhagen S, Denmark.
authors.forename: Anting Liu
authors.initials: AL
authors.lastname: Carlsen
authors.affiliation: Department of Experimental Medical Science, Protein Structure Bioinformatics, Lund University, Lund, Sweden.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Teku
authors.affiliation: Department of Autoimmunology & Biomarkers, Statens Serum Institut, Copenhagen S, Denmark.
authors.forename: Samantha O
authors.initials: SO
authors.lastname: Steen
authors.affiliation: Section of Rheumatology, Department of Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Wildt
authors.affiliation: Department of Experimental Medical Science, Protein Structure Bioinformatics, Lund University, Lund, Sweden.
authors.forename: Mauno
authors.initials: M
authors.lastname: Vihinen
authors.affiliation: Section of Rheumatology, Department of Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Roger
authors.initials: R
authors.lastname: Hesselstrand
authors.affiliation: Department of Autoimmunology & Biomarkers, Statens Serum Institut, Copenhagen S, Denmark, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital and Institute of Clinical Research, Clinical Biochemistry, University of Southern Denmark, Odense, Denmark.
authors.forename: Niels H H
authors.initials: NH
authors.lastname: Heegaard
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D003430:Cross-Sectional Studies; D004264:DNA Topoisomerases, Type I / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D010641:Phenotype; D012320:RNA Polymerase III / Q000276:immunology; D012342:RNA, Small Nuclear / Q000276:immunology; D012044:Regression Analysis; D012595:Scleroderma, Systemic / Q000097:blood* / Q000145:classification*; D013548:Sweden
chemical_list: D001323:Autoantibodies; D035683:MicroRNAs; D012342:RNA, Small Nuclear; C405483:U1 small nuclear RNA; D012320:RNA Polymerase III; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human
keywords: autoantibody; micro-RNA; plasma; scleroderma; systemic sclerosis