Increased expression of microRNA-155 in peripheral blood mononuclear cells from psoriasis patients is related to disease activity

Background MicroRNAs (miRNAs) gene expression regulators are altered in psoriasis suggesting their role in the pathogenesis. Objective To study expression changes of inflammation and toll-like receptor (TLR)-related miRNAs, miRNA-155, let-7i, miRNA-21, miRNA-146a and miRNA-223 in peripheral mononuclear cells (PBMCs) and miRNA-21, miRNA-146a and miRNA-223 in plasma, from chronic plaque-type psoriasis patients who were treatment-naive or had undergone a washout period (n = 11). MiRNAs were evaluated at baseline and after 11 (9-12) months [median (25th-75th percentile range)] of methotrexate (MTX) or topical (betamethasone plus calcipotriene) treatment. Methods MiRNA expression was analysed with quantitative real-time reverse transcription-polymerase chain reaction. Matched controls were studied. Results Psoriasis patients presented, at baseline, increased expression of miRNA-155, let-7i, miRNA-146a, miRNA-21 and miRNA-223 in PBMCs, plus miRNA-21, miRNA-146a and miRNA-223 in plasma. Receiver-operator characteristic (ROC) curve analysis and area under the curve (AUC) showed that expression of these miRNAs have the potential to distinguish between psoriasis and controls. At baseline, miRNA-155 expression in PBMCs correlated with Psoriasis Area Severity Index (PASI) [12 (8-14)] (Spearman r: 0.7140, P < 0.05) suggesting a role in psoriasis. After MTX or topical treatment, reduction in PASI was observed [87.5% (75-100)]; miRNA-155 expression in PBMCs decreased; plasma miRNA-21, miRNA-146a and miRNA-223 were down-regulated. ROC analysis showed that miRNA-155 expression in PBMCs from psoriasis patients have the potential to distinguish between patients' samples at baseline and after treatment (AUC: 0.942, sensitivity: 0.91; specificity: 0.91 values; maximum likelihood ratio = 10). After treatment, miRNA-146a expression in PBMCs increased; miRNA-155/miRNA-146a ratio decreased, suggestive of a regulatory feedback; let-7i expression decreased; miRNA-21 and miRNA-223 remained elevated. Conclusion In this exploratory study, psoriasis patients presented increased expression of miRNA-155 in PBMCs that correlated with PASI and decreased with disease remission. MiRNA-21, miRNA-146a and miRNA-223 in PBMCs and plasma were increased at baseline and differentially modulated, underscoring different roles of TLR-related miRNAs in psoriasis.European Commission-European Regional Development Fund (ERDF/FEDER), in collaboration with CSIC-PI-200820I216; Junta de Andalucia (JA), "Consejerias de Innovacion-Ciencia-Empresa y Educacion-Ciencia" (CVI 226, PC08-CTS-04046); ME-MICINN (SAF-2008-0368 and SAF-2011-27261); S. Garcia-Rodriguez: JAE-Doc-CSIC-Contract; Research Project 201420E095; G. Blasco-Morente: PhD Student of Clinical Medicine and Public Health Program, UGR; A. Rosal-Vela: Post-doctoral-contract from "Consejeria de Innovacion, Ciencia y Empresa", JA (P08-CTS-04046).Peer reviewe