SAT0287 SERUM CYTOKINE PROFILE IDENTIFIES PATHOMECHANISM AND EFFICIENT BIOMARKERS OF DISEASE ACTIVITY AND PROGNOSIS IN INTERSTITIAL PNEUMONIA COMBINED WITH POLYMYOSITIS/DERMATOMYOSITIS
Authors: Shogo Matsuda, Takuya Kotani, Takaaki Ishida, Youhei Fujiki, Takayasu Suzuka, Koji Nagai, Kenichiro Hata, Takeshi Shoda, Kentaro Isoda, Shigeki Makino, Tohru Takeuchi, Shigeki Arawaka
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> 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. <h3>Objectives:</h3> We measured serum cytokine levels before and during treatment of patients with PM/DM-ILD and examined the associated pathomechanism. <h3>Methods:</h3> 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. <h3>Results:</h3> 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. <h3>Conclusion:</h3> 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. <h3>References</h3> [1] Gono T, et al. Rheumatology (Oxford)2014;53:2196–203 [2] Oda K, et al. Sci Rep2017;7:1635. <h3>Disclosure of Interests:</h3> None declared