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Background: Polymyositis (PM) and dermatomyositis (DM) are idiopathic inflammatory myopathies that mainly involve the muscles, skin, lungs, and heart. PM/DM are frequently complicated by interstitial lung disease (ILD) that causes increased mortality. Anti-aminoacyl tRNA synthetase (ARS) antibody and anti-melanoma differentiation-associated gene 5 (MDA5) antibody are associated with complications of ILD. Anti-ARS antibody-positive PM/DM-ILD responds well to immunosuppressive therapy and has a good short-term prognosis but a high rate of relapse over the long term. In contrast, anti-MDA5 antibody-positive PM/DM-ILD responds poorly to immunosuppressive therapy, and its prognosis is poor. Recently, a number of cytokines have been implicated in the pathomechanism and outcome of PM/DM-ILD. High levels of serum IL-6, IL-8, IL-10, IL-18, CCL2, CXCL10, TNF-α, and IFN-α were detected in PM/DM-ILD cases, suggesting the pathological involvement of activated macrophages, type 1 T helper (Th1) cells, and neutrophils (ref 1, 2). However, investigation of the pathomechanism using serum cytokines remains insufficient in PM/DM-ILD. We hypothesised that multiple inflammatory cytokine pathways related to the above inflammatory cells would be involved in the pathomechanism of PM/DM-ILD. Objectives: We measured serum cytokine levels before and during treatment of patients with PM/DM-ILD and examined the associated pathomechanism. Methods: Serum cytokines were collected from 40 PM/DM-ILD patients. Principal components analysis (PCA) and cluster analysis were used to classify patients into subgroups. We compared cytokine profile of the survivors and dead patients as well as anti-MDA5 antibody-associated ILD and anti-ARS antibody-associated ILD. We also examined the association of various cytokines with disease activity indicators and prognosis of ILD. Results: PCA revealed that the diversity of cytokines was driven by three groups: (1) neutrophilic and M1-macrophage-driven cytokines, (2) Th1 cell-driven and M2-macrophage-induced cytokines, and (3) M2-macrophage-driven cytokine. Based on cluster analysis, patients were classified into two subgroups according to the cytokine levels of all groups (Figure A). Ninety percent of patients who died of ILD were included in clusters with high cytokine levels (Figure B). Serum cytokine levels of all groups were significantly higher in the anti-MDA5 antibody-positive patients than in the anti-ARS antibody-positive patients. Factors of poor prognosis in PM/DM-ILD correlated significantly with serum cytokine levels of groups 1 and 2. Among the 3 groups, serum cytokine levels of group 1 were significantly higher initially and at 2 and 4 weeks in the death group. Conclusion: These findings suggest that the activation of monocytes, macrophages, and Th1 cells, and neutrophils plays a role in the pathomechanism. Group 1 cytokines could be efficient biomarkers for predicting prognosis of PM/DM-ILD. References [1] Gono T, et al. Rheumatology (Oxford)2014;53:2196–203 [2] Oda K, et al. Sci Rep2017;7:1635. Disclosure of Interests: None declared

Background: Interstitial lung disease (ILD) associated with connective tissue disease is a life-threatening pathological condition that causes respiratory failure when it progresses. Lung inflammation is treated with corticosteroids and immunosuppressants, and pulmonary fibrosis is treated with anti-fibrosis agents such as pirfenidone and nintedanib. However, many cases are treatment-resistant and the outcome is poor. Moreover, adverse effects such as infections resulting from immunosuppressive therapy are problematic. The development of new treatments is thus required for ILD from the viewpoint of the poor effect and adverse effects of the currently available treatments. Research and development with adipose-derived stem cells (AdSCs) in immunosuppressive therapy have progressed for autoimmune diseases, and favorable outcomes have been reported. In recent years, the effectiveness of AdSCs in ILD model mice has been demonstrated (ref). The statin preparation has not only an angiogenesis promoting action, an immunosuppressive action, an anti-fibrotic action but also an action of promoting a cellular function including a migratory ability. Objectives: We have investigated the hypothesis that statin, an agent with pleiotropic effects, could augment the therapeutic potential of AdSCs. Methods: ILD was induced by bleomycin (BLM) in C57BL/6 mouse, and the mice were assigned in the following groups: 1) Control, 2) NP-AdSCs (2.5×104 cells), and 3) STNP-AdSCs (2.5×104 cells). Results: Simvastatin-conjugated nanoparticles (STNP) significantly promoted the migration activity and cell survival without changing the proliferation activity, and up-regulated transforming growth factor (TGF) -β1 in vitro assays. Lung inflammation and fibrosis assessed were significantly supressed at 4 weeks after starting BLM administration in STNP-AdSCs group (Figure). The levels of IL-4, IFN-gamma, TNF-alpha, COL1A1, and TIMP1 mRNA expression at 28 days after BLM administration were significantly lower in STNP-AdSCs group compared with that in other groups. Conclusion: Simvastatin-conjugated nanoparticles enhanced the therapeutic effect of a small number of AdSCs transplantation. Reference: [1] Sci Rep 6; 7 (1): 14608, 2017. Acknowledgement: This study was supported by Grants-in-Aid for Scientific Research-KAKENHI- of Japan (18K08160). Disclosure of Interests: None declared

Background: Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by microvascular damages and fibrosis. The main lesions of SSc are peripheral circulation insufficiency, sclerodermia, and interstitial pneumonia. Skin lesions are related to patient‘s ADL and QOL, however there is no effective treatment for normalizing the disease state. Adipose-derived stem cells (AdSCs) have recently been considered a useful treatment tool for autoimmune disease because of their anti-inflammatory and immunosuppressive effects (ref). Objectives: We investigated the therapeutic effect of intravenous mouse AdSCs (mAdSCs) transplantation in a SSc mouse model. Methods: SSc was induced by bleomycin (BLM) in Balb/c mice, and the mice were assigned in the following groups: 1. Control (BLM-SSc), 2. mAdSCs (1.0×104 cells), 3. mAdSCs (1.0×105 cells). After the administration of BLM, mAdSCs were injected via a tail vein on day 7. The mice were sacrificed at 14 days after mAdSCs injection, and the skins were harvested for histological analysis. Results: In mAdSCs (1.0×105 cells) group, thickening of skin, hydroxyproline content, infiltration of inflammatory cells, gene expression of inflammatory cytokines, and fibrotic factors were significantly reduced compared with control group (Figure). But in mAdSCs (1.0×104 cells) group, there were no reduction of them. mAdSCs did not accumulate in skin. The levels of MMP-2, MMP-9, and COL1A1 mRNA expression at 21 days after BLM administration were significantly lower in mAdSCs (1.0×105 cells) group compared with those in control group. Conclusion: Intravenous mAdSCs inhibited both skin inflammation and fibrosis of BLM-SSc mice in a dose-dependent manner. References: [1] Cell Transplant 2015.24: 2297-2305. [2] Journal of Autoimmunity, 2016. 70: 31-39. Acknowledgement: This study was supported by Grants-in-Aid for Scientific Research-KAKENHI- of Japan (Young Scientists B; 17K15761, 17K16216). Disclosure of Interests: None declared

Background Many cases of interstitial lung disease (ILD) complicated by microscopic polyangiitis (MPA) show the UIP pattern on chest HRCT, being similar to idiopathic pulmonary fibrosis (IPF/UIP), and the associated prognosis is poor compared with that of MPA without ILD.1 However, the details have not been fully clarified. Objectives Prognostic factors of MPA-ILD sufficiently treated with immunosuppressive therapy were investigated. Methods Of consecutive patients with MPA who received inpatient treatment at our hospitals between 2001 and 2016, MPO-ANCA-positive patients who met the 2007 EMEA classification criteria and had concomitant ILD on HRCT were selected as the subjects. Using the clinical data and HRCT fibrosis score,2 the outcome and prognostic factors were retrospectively investigated. Results The subjects were 65 patients with MPA-ILD, 31 and 34 patients were male and female, respectively, and the median age (interquartile range) was 7367–76 years old. At the time of treatment initiation, MPO-ANCA was 129 (50.9–359) EU; KL-6, 461 (289–665) U/mL; Aa-DO2, 25.1 (15.6–34.2);%FVC, 81.2 (67.8–93.9)%; and%DLco/VA, 62.7 (45.3–73.2)%. On HRCT, the UIP and non-UIP patterns were observed in 44 and 21 patients, respectively. In treatment, prednisolone was administered to 63 patients, immunosuppressants were used in 55 patients, and blood purification therapy was concomitantly administered to 9 patients. MPO-ANCA on the final follow-up was lower than the detection sensitivity in 56 patients. The outcome was death in 23 patients, and the 5- and 10 year survival rates after treatment initiation were 69.8% and 51.1%, respectively (acute exacerbation of interstitial pneumonia: 5 patients, infection and alveolar haemorrhage: 3, infection: 1, pneumothorax: 1, lung cancer: 2, pulmonary hypertension: 1, sudden death: 4, heart failure: 2, renal failure: 2, cerebral haemorrhage: 1, intestinal haemorrhage: 1). Regarding lung disease-related death, the age (p=0.018),%FVC (p=0.026), HRCT fibrosis score (p Conclusions Many MPA-ILD patients showed the UIP pattern, but their prognosis was better than that of previously reported IPF/UIP patients, suggesting that early immunosuppressive therapy is effective. However, expansion of fibrosis was included in the factors indicating a poor prognosis, suggesting the limit of immunosuppressive therapy. References [1] Fernandez Casares M, Gonzalez A, et al. Microscopic polyangiitis associated with pulmonary fibrosis. Clin Rheumatol. 2015;34(7):1273–7. [2] Wells AU, Hansell DM, Rubens MB, et al. Fibrosing alveolitis in systemic sclerosis: indices of lung function in relation to extent of disease on computed tomography. Arthritis Rheum1997;40:1229–36. Disclosure of Interest None declared