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

作者：Nakashima Ran; Imura Yoshitaka; Kobayashi Shio; Yukawa Naoichiro; Yoshifuji Hajime; Nojima Takaki; Kawabata Daisuke; Ohmura Koichiro; Usui Takashi; Fujii Takao; Okawa Katsuya; Mimori Tsuneyo^*

来源：Rheumatology, 2010, 49(3): 433-440.

DOI：10.1093/rheumatology/kep375

• Anti-CADM-140 antibody
• Amyopathic dermatomyositis
• Interferon induced with helicase C domain protein 1
• Interstitial lung disease
• Ferritin
• Innate immunity
• Virus

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 [(35)S]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.

• 出版日期2010-3