title: Classification of idiopathic interstitial pneumonias using anti-myxovirus resistance-protein 1 autoantibody.
abstract: Chronic fibrosing idiopathic interstitial pneumonia (IIP) can be divided into two main types: idiopathic pulmonary fibrosis (IPF), a steroid-resistant and progressive disease with a median survival of 2-3 years, and idiopathic non-specific interstitial pneumonia (INSIP), a steroid-sensitive and non-progressive autoimmune disease. Although the clinical courses of these two diseases differ, they may be difficult to distinguish at diagnosis. We performed a comprehensive analysis of serum autoantibodies from patients definitively diagnosed with IPF, INSIP, autoimmune pulmonary alveolar proteinosis, and sarcoidosis. We identified disease-specific autoantibodies and enriched KEGG pathways unique to each disease, and demonstrated that IPF and INSIP are serologically distinct. Furthermore, we discovered a new INSIP-specific autoantibody, anti-myxovirus resistance-1 (MX1) autoantibody. Patients positive for anti-MX1 autoantibody constituted 17.5% of all cases of chronic fibrosing IIPs. Notably, patients rarely simultaneously carried the anti-MX1 autoantibody and the anti-aminoacyl-transfer RNA synthetase autoantibody, which is common in chronic fibrosing IIPs. Because MX1 is one of the most important interferon-inducible anti-viral genes, we have not only identified a new diagnostic autoantibody of INSIP but also obtained new insight into the pathology of INSIP, which may be associated with viral infection and autoimmunity.
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Hamano
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.|AMED, CREST, Suita City, Osaka 565-0871, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kida
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ihara
authors.affiliation: Medical &Biological Laboratories Co., Ltd., Ina Laboratory, 1063-103 Terasawaoka, Ina City, Nagano 396-0002, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Murakami
authors.affiliation: Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yanagawa
authors.affiliation: Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Honda
authors.affiliation: National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saitoasagi, Ibaraki City, Osaka 567-0085, Japan.
authors.forename: Lokesh P
authors.initials: LP
authors.lastname: Tripathi
authors.affiliation: National Hospital Organization Kinki-Chuo Chest Medical Center, 1180 Nagasone-Cho, Kita-Ku, Sakai City, Osaka 591-8555, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Arai
authors.affiliation: National Hospital Organization Kinki-Chuo Chest Medical Center, 1180 Nagasone-Cho, Kita-Ku, Sakai City, Osaka 591-8555, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Hirose
authors.affiliation: Office of Biostatistics and Data Management, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita City, Osaka 565-8565, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Hamasaki
authors.affiliation: National Hospital Organization Toneyama National Hospital, 5-1-1 Toneyama, Toyonaka City, Osaka 560-8552, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Yano
authors.affiliation: Department of Immunopathology, WPI Immunology Frontier Research Center, Osaka University, Yamadaoka 3-1, Suita City, Osaka 565-0871, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.|AMED, CREST, Suita City, Osaka 565-0871, Japan.|Department of Immunopathology, WPI Immunology Frontier Research Center, Osaka University, Yamadaoka 3-1, Suita City, Osaka 565-0871, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.|AMED, CREST, Suita City, Osaka 565-0871, Japan.|Department of Immunopathology, WPI Immunology Frontier Research Center, Osaka University, Yamadaoka 3-1, Suita City, Osaka 565-0871, Japan.
authors.forename: Hyota
authors.initials: H
authors.lastname: Takamatsu
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.|AMED, CREST, Suita City, Osaka 565-0871, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Otsuka
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.|AMED, CREST, Suita City, Osaka 565-0871, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Minami
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.|AMED, CREST, Suita City, Osaka 565-0871, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Hirata
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.|AMED, CREST, Suita City, Osaka 565-0871, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.|AMED, CREST, Suita City, Osaka 565-0871, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Nagatomo
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.|AMED, CREST, Suita City, Osaka 565-0871, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Takeda
authors.affiliation: National Hospital Organization Toneyama National Hospital, 5-1-1 Toneyama, Toyonaka City, Osaka 560-8552, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Yamadaoka 3-1, Suita City, Osaka 565-0871, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Nishikawa
authors.affiliation: National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saitoasagi, Ibaraki City, Osaka 567-0085, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Mizuguchi
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.|AMED, CREST, Suita City, Osaka 565-0871, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kijima
authors.affiliation: National Hospital Organization Kinki-Chuo Chest Medical Center, 1180 Nagasone-Cho, Kita-Ku, Sakai City, Osaka 591-8555, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kitaichi
authors.affiliation: Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Tomiyama
authors.affiliation: National Hospital Organization Kinki-Chuo Chest Medical Center, 1180 Nagasone-Cho, Kita-Ku, Sakai City, Osaka 591-8555, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.|AMED, CREST, Suita City, Osaka 565-0871, Japan.|Department of Immunopathology, WPI Immunology Frontier Research Center, Osaka University, Yamadaoka 3-1, Suita City, Osaka 565-0871, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
mesh_terms: D000328:Adult; D000368:Aged; D000604:Amino Acyl-tRNA Synthetases / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D005260:Female; D006801:Humans; D054988:Idiopathic Interstitial Pneumonias / Q000145:classification* / Q000175:diagnosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D000604:Amino Acyl-tRNA Synthetases