Norimoto Kobayashi1, Shunichiro Takezaki1, Ichiro Kobayashi2, Naomi Iwata1, Masaaki Mori1, Kazushige Nagai1, Naoko Nakano1, Mari Miyoshi1, Noriko Kinjo1, Takuji Murata1, Kenji Masunaga1, Hiroaki Umebayashi1, Tomoyuki Imagawa1, Kazunaga Agematsu1, Shinji Sato1, Masataka Kuwana1, Masafumi Yamada1, Shuji Takei1, Shumpei Yokota1, Kenichi Koike1, Tadashi Ariga1. 1. Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center, Ohbu, Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama, Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Department of Pediatrics, Ehime University Graduate School of Medicine, Matsuyama, Department of Allergy & Immunology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Department of Pediatrics, University of the Ryukyus, Naha, Department of Pediatrics, Osaka Medical College, Takatsuki, Department of Pediatrics, Kurume University School of Medicine, Kurume, Department of General Pediatrics, Miyagi Children's Hospital, Sendai, Division of Infection, Immunology and Rheumatology, Kanagawa Children's Medical Center, Yokohama, Department of Infection and Host Defense, Shinshu University Graduate School of Medicine, Matsumoto, Department of Rheumatology, Tokai University School of Medicine, Isehara, Department of Rheumatology, Keio University School of Medicine, Tokyo and School of Health Science, Faculty of Medicine, Kagoshima University, Kagoshima, Japan. 2. Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center, Ohbu, Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama, Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Department of Pediatrics, Ehime University Graduate School of Medicine, Matsuyama, Department of Allergy & Immunology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Department of Pediatrics, University of the Ryukyus, Naha, Department of Pediatrics, Osaka Medical College, Takatsuki, Department of Pediatrics, Kurume University School of Medicine, Kurume, Department of General Pediatrics, Miyagi Children's Hospital, Sendai, Division of Infection, Immunology and Rheumatology, Kanagawa Children's Medical Center, Yokohama, Department of Infection and Host Defense, Shinshu University Graduate School of Medicine, Matsumoto, Department of Rheumatology, Tokai University School of Medicine, Isehara, Department of Rheumatology, Keio University School of Medicine, Tokyo and School of Health Science, Faculty of Medicine, Kagoshima University, Kagoshima, Japan ichikobaya@med.hokudai.ac.jp.
Abstract
OBJECTIVE: Rapidly progressive interstitial lung disease (RP-ILD) is a rare but potentially fatal complication of JDM. The aim of this study was to establish markers for the prediction and early diagnosis of RP-ILD associated with JDM. METHODS: The clinical records of 54 patients with JDM were retrospectively reviewed: 10 had RP-ILD (7 died, 3 survived), 19 had chronic ILD and 24 were without ILD. Routine tests included a high-resolution CT (HRCT) scan of the chest and measurement of serum levels of creatine phosphokinase, ferritin and Krebs von den Lungen-6 (KL-6). Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies and IL-18 levels were measured by ELISA. RESULTS: No differences were found in the ratio of juvenile clinically amyopathic DM between the three groups. Initial chest HRCT scan findings were variable and could not distinguish between RP-ILD and chronic ILD. Anti-MDA5 antibodies were positive in all 8 patients with RP-ILD and 10 of 14 with chronic ILD, but none of the patients without ILD. Serum levels of anti-MDA5 antibody, ferritin, KL-6 and IL-18 were significantly higher in the RP-ILD group than in the chronic ILD and non-ILD groups. Serum levels of IL-18 positively correlated with serum KL-6 (R = 0.66, P < 0.001). CONCLUSION: High serum levels of IL-18, KL-6, ferritin and anti-MDA5 antibodies (e.g. >200 units by ELISA) are associated with RP-ILD. These can be used as an indication for early intensive treatment. Both alveolar macrophages and autoimmunity to MDA5 are possibly involved in the development of RP-ILD associated with JDM.
OBJECTIVE: Rapidly progressive interstitial lung disease (RP-ILD) is a rare but potentially fatal complication of JDM. The aim of this study was to establish markers for the prediction and early diagnosis of RP-ILD associated with JDM. METHODS: The clinical records of 54 patients with JDM were retrospectively reviewed: 10 had RP-ILD (7 died, 3 survived), 19 had chronic ILD and 24 were without ILD. Routine tests included a high-resolution CT (HRCT) scan of the chest and measurement of serum levels of creatine phosphokinase, ferritin and Krebs von den Lungen-6 (KL-6). Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies and IL-18 levels were measured by ELISA. RESULTS: No differences were found in the ratio of juvenile clinically amyopathic DM between the three groups. Initial chest HRCT scan findings were variable and could not distinguish between RP-ILD and chronic ILD. Anti-MDA5 antibodies were positive in all 8 patients with RP-ILD and 10 of 14 with chronic ILD, but none of the patients without ILD. Serum levels of anti-MDA5 antibody, ferritin, KL-6 and IL-18 were significantly higher in the RP-ILD group than in the chronic ILD and non-ILD groups. Serum levels of IL-18 positively correlated with serum KL-6 (R = 0.66, P < 0.001). CONCLUSION: High serum levels of IL-18, KL-6, ferritin and anti-MDA5 antibodies (e.g. >200 units by ELISA) are associated with RP-ILD. These can be used as an indication for early intensive treatment. Both alveolar macrophages and autoimmunity to MDA5 are possibly involved in the development of RP-ILD associated with JDM.
Authors: Lisa G Rider; Rohit Aggarwal; Pedro M Machado; Jean-Yves Hogrel; Ann M Reed; Lisa Christopher-Stine; Nicolino Ruperto Journal: Nat Rev Rheumatol Date: 2018-04-12 Impact factor: 20.543
Authors: Sara Sabbagh; Adriana Almeida de Jesus; SuJin Hwang; Hye Sun Kuehn; Hanna Kim; Lawrence Jung; Ruy Carrasco; Sergio Rosenzweig; Raphaela Goldbach-Mansky; Lisa G Rider Journal: Brain Date: 2019-11-01 Impact factor: 13.501