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FRI0440 Increased Messenger RNA Levels of the Mesenchymal Cadherin-11 in the Peripheral Blood Correlate with Diffuse Skin Involvement in Systemic Sclerosis

Background The mesencymal cadherin-11 is a cell-cell adhesion molecule also involved in cellular migration and invasion. Experimental studies have implicated a pathogenetic role of this molecule in inflammatory arthritis and in fibrosing conditions. Moreover, in the skin of patients with the prototypic human fibrotic disease, namely systemic sclerosis (SSc), cadherin-11 is hyper-expressed on dermal fibroblasts and resident macrophages, whereas the increased respective mRNA levels correlate with the modified Rodnan skin thickness scores (1). Objectives To examine whether cadherin-11 gene expression can be also identified in cells that circulate in SSc peripheral blood. Methods Cadherin-11 mRNA was quantified by real-time reverse transcription-polymerase chain reaction as previously described (2), in 3 ml blood samples obtained from 71 SSc patients (aged 53±2 years, 65 women) and 35 control non-SSc patients with Raynaud's phenomenon, without active synovitis at the time of sampling. Results Cadherin-11 mRNA transcripts were detected in blood samples from 39% of patients with diffuse SSc, versus 16% in those with limited SSc, versus 6% and 16% in patients with idiopathic or associated with other connective tissue diseases Raynaud's phenomenon, respectively (p=0.049). Cadherin-11 mRNA levels in SSc patients were increased by 3.74-fold comparing to controls (p=0.036). By multivariate logistic regression analysis we found that diffuse skin involvement correlated with cadherin-11 mRNA positivity (p=0.028), independently of age, gender, disease duration, lung involvement, digital ulcers, inflammatory indices or anti-Scl-70 autoantibody presence. A similar independent correlation of diffuse SSc was also observed with increased (considered arbitrarily as ≥3-fold of average non-SSc levels) individual levels of cadherin-11 mRNA (p=0.011). Conclusions Cadherin-11 is hyper-expressed at the mRNA level in the peripheral blood of patients with diffuse SSc, further supporting the notion that cadherin-11 may be a legitimate therapeutic target. Studies on the origin and possible pathogenic function of these circulating cells may shed light into the complex pathogenesis of SSc. References Wu M, et al. Identification of cadherin-11 as a mediator of dermal fibrosis and possible role in systemic sclerosis. Arthritis Rheum 2014;66(4):1010-21. Sfikakis PP, et al. Cadherin-11 mRNA transcripts are frequently found in rheumatoid arthritis peripheral blood and correlate with established polyarthritis. Clin Immunol. 2014;155(1):33-41. Disclosure of Interest None declared