The RIG-I-like receptor IFIH1/MDA5 is a dermatomyositis-specific autoantigen identified by the anti-CADM-140 antibody

• Published in: Rheumatology (Oxford, England) England), 2010-03, Vol.49 (3), p.433-440
• Main Authors: Nakashima, Ran, Imura, Yoshitaka, Kobayashi, Shio, Yukawa, Naoichiro, Yoshifuji, Hajime, Nojima, Takaki, Kawabata, Daisuke, Ohmura, Koichiro, Usui, Takashi, Fujii, Takao, Okawa, Katsuya, Mimori, Tsuneyo
• Format: Article
• Language: English
• Subjects: Adult; Amino Acid Sequence; Amyopathic dermatomyositis; Anti-CADM-140 antibody; Autoantibodies - immunology; Autoantigens - blood; Biological and medical sciences; Biomarkers - blood; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - immunology; Dermatomyositis - immunology; Diseases of the osteoarticular system; Ferritin; HeLa Cells; Humans; Immunity, Innate; Innate immunity; Interferon induced with helicase C domain protein 1; Interferon-Induced Helicase, IFIH1; Interstitial lung disease; Medical sciences; Molecular Sequence Data; Peptides - immunology; Pneumology; Respiratory system : syndromes and miscellaneous diseases; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Virus
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/kep375

Objectives. Various autoantibodies are detected in the sera of PM/DM patients. Some of them are specific to PM/DM patients and closely associated with clinical manifestations of the diseases. Recently, the anti-CADM-140 antibody was reported to be found specifically in clinically amyopathic DM (C-ADM) patients and to be associated with acute interstitial lung disease (ILD). We assessed the clinical significance of the anti-CADM-140 antibody and then investigated the autoantigen recognized by the anti-CADM-140 antibody. Methods. Autoantibodies were screened in 192 patients with various CTDs and 21 healthy controls using immunoprecipitation with [35S]methionine-labelled HeLa cells. Immunoabsorbent column chromatography was used to purify an autoantigen that was subsequently subjected to peptide mass fingerprinting. Results. The anti-CADM-140 antibody was revealed to be specific to DM. Most of the anti-CADM-140-positive patients were C-ADM although some of them showed apparent myositis. The anti-CADM-140-positive patients frequently showed hyperferritinaemia and acute progressive ILD with poor prognosis. The anti-CADM-140 antibody was shown to recognize IFN induced with helicase C domain protein 1 (IFIH1), also known as the melanoma differentiation-associated gene 5 (MDA5), which is one of the RIG-I-like receptors and plays a role in innate immune responses. Conclusion. The anti-CADM-140 antibody was a marker of DM and intractable ILD and recognized IFIH1/MDA5, which is involved in innate immunity. These findings may give a new insight into the pathogenesis of DM.