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Abstract Number: 2144

Multiple Serum Cytokine and Chemokine Profiling to Identify Combinational Biomarkers Toward Patients of Polymyositis/Dermatomyositis Complicated with Rapidly Progressive Interstitial Lung Disease

Toshimasa Shimizu1, Tomohiro Koga1,2, Yoshiro Horai3, Keita Fujikawa4, Yushiro Endo1, Sousuke Tsuji1, Ayuko Takatani1, Masataka Umeda1, Shoichi Fukui1, Remi Sumiyoshi1, Ayako Nishino1, Shinya Kawashiri1, Naoki Iwamoto1, Takashi Igawa1, Kunihiro Ichinose1, Mami Tamai1, Noriho Sakamoto5, Hideki Nakamura1, Tomoki Origuchi6, Hiroshi Mukae5, Masataka Kuwana7 and Atsushi Kawakami1, 1Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, 2Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki City, Japan, 3Department of Rheumatology, National Hospital Nagasaki Medical Center, Nagasaki, Japan, 4Japan Community Health care Organization Isahaya General Hospital, Nagasaki, Japan, 5Department of RespiratoryMedicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, 6Department of Rehabilitation Sciences, Nagasaki University, Nagasaki, Japan, 7Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: interstitial lung disease and myositis

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Session Information

Date: Tuesday, November 7, 2017

Title: Muscle Biology, Myositis and Myopathies Poster

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Polymyositis (PM)/dermatomyositis (DM) is a chronic inflammatory disorders involved in skeletal muscles. Interstitial lung disease (ILD) complicated with PM/DM patients is often developed as rapidly progressive ILD (RPILD), which can be treatment resistant and life threatening. However, serum biomarkers of PM/DM with RPILD still remain to be obscure. This study was aimed to identify the specific biomarkers to assess PM/DM complicated with RPILD.

Methods: Forty-six patients with PM/DM-ILD, in either RPILD (n = 20) or chronic ILD (n = 26), were enrolled from Nagasaki University Hospital and related institutions. They gave their informed consent to be subjected to the protocol that was approved by the Institutional Review Board of Nagasaki University. Using medical records, we analyzed the patientfs demographics and clinical characteristics. Serum levels of 42 cytokines/chemokines were measured by multi-suspension cytokine array. Serum levels of anti-melanoma differentiation-associated gene 5 (MDA5) antibody, ferritin and interferon-alpha (IFN- alpha) were measured by enzyme linked immunosorbent assay. These serum variables were ranked by their importance by a multivariate classification algorithm termed random forest analysis. We performed a logistic regression analysis to determine a set of specific biomarkers for distinguishing patients with RPILD from patients with chronic ILD.

Results: Patients with RPILD had significantly higher age, mortality, the frequency of clinically amyopathic DM (CADM), the prevalence of mediastinal emphysema, periungual erythema and mechanicfs hand than patients with chronic ILD. Twenty-four out of 42 cytokines/chemokines, anti-MDA5 antibody, ferritin and IFN- alpha were available for further analyses. Patients with RPILD had significantly higher serum levels of 5 cytokines (IL-15, IL-6, CCL7, CXCL10 and VCAM-1), anti-MDA5 antibody and ferritin than patients with chronic ILD patients whereas CCL-22 was significantly low in RPILD patients. We found that IL15 was most significant cytokine to distinguish patients with RPILD from patients with chronic ILD using random forest analysis (Fig. 1). Additionally, we found that anti-MDA5 antibody, IL-15, TNF- alpha, CXCL-8, CCL-22 and IL-RA were the best combination to distinguish patients with RPILD from patients with chronic ILD (sensitivity: 95%, specificity: 88.5%, accuracy: 91.3%).

Conclusion: Our data for the first time identify the combinational serum biomarkers to predict PM/DM patients complicated with RPILD.


Disclosure: T. Shimizu, None; T. Koga, None; Y. Horai, None; K. Fujikawa, None; Y. Endo, None; S. Tsuji, None; A. Takatani, None; M. Umeda, None; S. Fukui, None; R. Sumiyoshi, None; A. Nishino, None; S. Kawashiri, None; N. Iwamoto, None; T. Igawa, None; K. Ichinose, None; M. Tamai, None; N. Sakamoto, None; H. Nakamura, None; T. Origuchi, None; H. Mukae, None; M. Kuwana, Medical & Biological Laboratories, Co., Ltd, 7; A. Kawakami, None.

To cite this abstract in AMA style:

Shimizu T, Koga T, Horai Y, Fujikawa K, Endo Y, Tsuji S, Takatani A, Umeda M, Fukui S, Sumiyoshi R, Nishino A, Kawashiri S, Iwamoto N, Igawa T, Ichinose K, Tamai M, Sakamoto N, Nakamura H, Origuchi T, Mukae H, Kuwana M, Kawakami A. Multiple Serum Cytokine and Chemokine Profiling to Identify Combinational Biomarkers Toward Patients of Polymyositis/Dermatomyositis Complicated with Rapidly Progressive Interstitial Lung Disease [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/multiple-serum-cytokine-and-chemokine-profiling-to-identify-combinational-biomarkers-toward-patients-of-polymyositisdermatomyositis-complicated-with-rapidly-progressive-interstitial-lung-disease/. Accessed .
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