SAT0287 SERUM CYTOKINE PROFILE IDENTIFIES PATHOMECHANISM AND EFFICIENT BIOMARKERS OF DISEASE ACTIVITY AND PROGNOSIS IN INTERSTITIAL PNEUMONIA COMBINED WITH POLYMYOSITIS/DERMATOMYOSITIS. (June 2019)

• Record Type: Journal Article
• Authors: Matsuda, Shogo; Kotani, Takuya; Ishida, Takaaki; Fujiki, Youhei; Suzuka, Takayasu; Nagai, Koji; Hata, Kenichiro; Shoda, Takeshi; Isoda, Kentaro; Makino, Shigeki; Takeuchi, Tohru; Arawaka, Shigeki
• Is Part Of: Annals of the rheumatic diseases. Volume 78(2019)Supplement 2
• Page Start: 1220
• Page End: 1221
• Publication Date: 2019-06
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2019-eular.6614
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : 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