Circulating MicroRNA Expression Profiles Associated With Systemic Lupus Erythematosus
2013 (English)In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, no 5, 1324-1334 p.Article in journal (Refereed) Published
Objective To evaluate the specificity of expression patterns of cell-free circulating microRNAs (miRNAs) in systemic lupus erythematosus (SLE). Methods Total RNA was purified from plasma, and 45 different specific, mature miRNAs were determined using quantitative reverse transcriptionpolymerase chain reaction assays. A total of 409 plasma samples were obtained from 364 different patients with SLE, healthy control subjects, and control subjects with other autoimmune diseases. The results in the primary cohort of 62 patients with SLE and 29 healthy control subjects were validated in 2 independent cohorts: a validation cohort comprising 68 patients with SLE and 68 healthy control subjects, and a disease control cohort comprising 20 patients with SLE (19 of whom were from the other validation cohort), 46 healthy control subjects, 38 patients with vasculitis, 18 patients with rheumatoid arthritis, and 20 immunosuppressed patients. Results Seven miRNAs were statistically significantly differentially expressed in plasma from patients with SLE. The expression of miRNA-142-3p (miR-142-3p) and miR-181a was increased, and the expression of miR-106a, miR-17, miR-20a, miR-203, and miR-92a was decreased. In addition, the expression of miR-342-3p, miR-223, and miR-20a was significantly decreased in SLE patients with active nephritis. A predictive model for SLE based on 2 or 4 miRNAs differentiated patients with SLE from control subjects (76% accuracy) when validated independently (P andlt; 2 x 109). Use of the 4-miRNA model provided highly significant differentiation between the SLE group and disease controls, except for those with vasculitis. Conclusion Circulating miRNAs are systematically altered in SLE. A 4-miRNA signature was diagnostic of SLE, and a specific subset of miRNA profiles was associated with nephritis. All of the signature miRNAs target genes in the transforming growth factor signaling pathways. Other targets include regulation of apoptosis, cytokinecytokine receptors, T cell development, and cytoskeletal organization. These findings highlight possible dysregulated pathways in SLE and suggest that circulating miRNA patterns distinguish SLE from other immunoinflammatory phenotypes.
Place, publisher, year, edition, pages
Wiley-Blackwell , 2013. Vol. 65, no 5, 1324-1334 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-93391DOI: 10.1002/art.37890ISI: 000318170600023OAI: oai:DiVA.org:liu-93391DiVA: diva2:624494
Funding Agencies|Danish Rheumatism Association|R99-A1937R33-A1836|National Cancer Institute, NIH||Medical Faculty at Lund University||Alfred Osterlund Foundation||Crafoord Foundation||Swedish Rheumatism Association||Greta and Johan Kock Foundation||King Gustaf Vs 80-Year Foundation||Swedish Society of Medicine||Foundation of the Swedish National Board of Health and Welfare||Skane University Hospital, Lund, Sweden||A. P. Moller Foundation||Region of Southern Denmark||Swedish Renal Foundation||Swedish Research Council||Novo Nordisk Research Foundation||Foundation for the Advancement of Medical Science||2013-05-312013-05-312014-02-28