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


CONCLUSIONS
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.
Nakashima
Ran
R
Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Imura
Yoshitaka
Y
Kobayashi
Shio
S
Yukawa
Naoichiro
N
Yoshifuji
Hajime
H
Nojima
Takaki
T
Kawabata
Daisuke
D
Ohmura
Koichiro
K
Usui
Takashi
T
Fujii
Takao
T
Okawa
Katsuya
K
Mimori
Tsuneyo
T
D000328:Adult; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology*; D003882:Dermatomyositis / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D036341:Intercellular Signaling Peptides and Proteins; D000072640:Interferon-Induced Helicase, IFIH1; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; C501597:CADM-140 peptide, human; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1