POS0426 CIRCULATING MICRORNA PROFILING IN PATIENTS WITH ANTI-SYNTHETASE SYNDROME AND INTERSTITIAL LUNG DISEASE
Authors: G. Zanframundo, S. Bozzini, V. Codullo, V. Frangipane, L. Pandolfi, B. Atienza-Mateo, S. Remuzgo Martinez, C. Montecucco, M. A. González-Gay, F. Meloni, L. Cavagna
Journal: Annals of the Rheumatic Diseases (2021)

Background: Anti-synthetase syndrome (ASSD) is an autoimmune disease characterized by autoantibodies against one of many aminoacyl transfer RNA (tRNA) synthetases. Interstitial Lung Disease (ILD) in ASSD patients is frequent, often severe and rapidly progressive, causing much of the increased morbidity and mortality associated with ASSD as compared to other idiopathic inflammatory myopathies [1]. Objectives: In this study, we hypothesized that immune-related miRNAs may be associated with presence/absence of lung involvement in patients with ASSD and help predict disease course. Methods: A total of 15 ASSD patients were enrolled: 11 with ILD and 4 without ILD. Differentially expressed miRNAs were identified in plasma derived-exosome, using miRNA PCR array (MIHS-111ZG, Qiagen) including 84 miRNAs involved in activation and differentiation of T and B cells. Results: Among all miRNAs analyzed we found that miR-15b-5p, miR-23a-3p, miR-25-3p, miR-30a-5p and miR29c-3p were up-regulated in ASSD-ILD patients (p&lt;0.05) as compared to patients without lung involvement (Figure 1). To evaluate the effectiveness of the five miRNAs for predicting ILD among ASSD patients, ROC curves were constructed. The AUCs of miR-15b-5p, miR-25-3p, miR-30a-5p and miR29c-3p were 0.83, 0.87, 0.86 and 0.89, respectively (p= 0.05 for miR-25-3p and p&lt;0.05 for all other curves). The prediction of the biologic targets and pathways as well as cellular processes by DIANA-mirPath analysis showed that all miRNAs associated with ILD presence are involved in PI3K-Akt signaling pathway. Conclusion: Our study shows that, in ASSD patients with ILD, miR-15b-5p, miR-23a-3p, miR-25-3p, miR-30a-5p and miR29c-3p were up-regulated compared to patients without evidence of ILD. A clear involvement in immune and inflammatory diseases was documented for the miRNAs identified [2] and, for many of these, studies in the literature indicate a possible role in pulmonary fibrosis [3]. It is notable that these miRNAs were related to PI3K-Akt signaling pathway that regulate cell proliferation, differentiation and apoptosis [4]. It has also been demonstrated that in lung fibroblast the PI3K–Akt signals can be aberrantly activated [5]. The identification of markers could be important in the early identification of the disease and for its treatment. References: [1]Kalluri M, Oddis CV. Pulmonary manifestations of the idiopathic inflammatory myopathies. Clinics in chest medicine. 2010; 31:501–512. [2]Prabahar A, Natarajan J, ImmunemiR-a database of prioritized immune miRNA disease associations and its interactome. MicroRNA, 2017; 6: 71–78. [3]Sessa R, Hata A. Role of microRNAs in lung development and pulmonary diseases. Pulm Circ. 2013; 3:315-28. [4]Ersahin T, Tuncbag N, Cetin-Atalay R. The PI3K/AKT/mTOR interactive pathway. Mol Biosyst. 2015;11:1946-54. [5]Zhang XL, Xing RG, Chen L, Liu CR, Miao ZG. PI3K/Akt signaling is involved in the pathogenesis of bleomycin-induced pulmonary fibrosis via regulation of epithelial-mesenchymal transition. Mol Med Rep. 2016;14:5699-5706. Figure 1. Comparison of relative levels of five miRNAs among patients with and without lung involvement were expressed as log 2 transformed values. * p&lt;0.05; ** p&lt;0.01 Disclosure of Interests: None declared