title: Splicing factor proline/glutamine-rich is a novel autoantigen of dermatomyositis and associated with anti-melanoma differentiation-associated gene 5 antibody.
abstract: Anti-MDA5 antibody positive dermatomyositis (DM) and clinically amyopathic DM (CADM) often develop into rapidly progressive interstitial lung disease, but their pathogenesis remains unclear. We observed that sera from DM/CADM patients immunoprecipitated a common 110 kDa polypeptide. We investigated this autoantigen and its clinical significance.
  
  
  
  Autoantibodies were screened in 333 patients with various connective tissue diseases (CTDs) and 20 healthy controls (HCs) by immunoprecipitation with [35S]methionine-labeled HeLa cells. Immunoabsorbent column chromatography was used to purify the reactive autoantigen which was subsequently analyzed by peptide mass fingerprinting.
  
  
  
  Anti-110 kDa antibody was detected in sera from 27 DM/CADM patients, but not in sera from other CTD patients or HCs. All patients with anti-110 kDa antibody had anti-MDA5 antibody. The maximum KL-6 levels in anti-110 kDa antibody-positive patients were higher than in anti-110 kDa antibody-negative patients, and all anti-MDA5-antibody-positive patients who showed the recurrence of DM/CADM were anti-110 kDa antibody-positive. The corresponding autoantigen was identified as splicing factor proline/glutamine-rich protein (SFPQ). In some cases, anti-SFPQ antibody was detected at diagnosis (early-detected group), but in other cases, it appeared during the disease course (delayed-detected group). The diagnosis timing of DM/CADM showed seasonal patterns according to the timing of anti-SFPQ antibody appearance. Specifically, 77% (10/13) of patients were diagnosed between August and October in the early-detected group, while 57% (8/14) of patients were diagnosed between January and March in the delayed-detected group.
  
  
  
  Some anti-MDA5 antibody-positive patients had an antibody to SFPQ, which is known to play a role in innate immune responses. Anti-SFPQ antibody may be involved in the chronic disease course of DM/CADM. The diagnosis timing of DM/CADM in anti-MDA5 antibody-positive patients showed seasonal patterns according to the timing of anti-SFPQ antibody appearance. These findings may provide new insights into the pathogenesis of DM/CADM.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: hosono25@kuhp.kyoto-u.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hosono
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: ranran@kuhp.kyoto-u.ac.jp.
authors.forename: Ran
authors.initials: R
authors.lastname: Nakashima
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, 7-6-8 Saitoasagi, Ibaraki City, Osaka 567-0085, Japan. Electronic address: serada@nibiohn.go.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Serada
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: kosaku@kuhp.kyoto-u.ac.jp.
authors.forename: Kosaku
authors.initials: K
authors.lastname: Murakami
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: imuray@kuhp.kyoto-u.ac.jp.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Imura
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: yossii@kuhp.kyoto-u.ac.jp.
authors.forename: Hajime
authors.initials: H
authors.lastname: Yoshifuji
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: ohmurako@kuhp.kyoto-u.ac.jp.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ohmura
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, 7-6-8 Saitoasagi, Ibaraki City, Osaka 567-0085, Japan. Electronic address: tnaka@nibiohn.go.jp.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Naka
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: mimorit@kuhp.kyoto-u.ac.jp.
authors.forename: Tsuneyo
authors.initials: T
authors.lastname: Mimori
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D015415:Biomarkers; D016022:Case-Control Studies; D003240:Connective Tissue Diseases / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism; D003882:Dermatomyositis / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D000072670:PTB-Associated Splicing Factor / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D063189:Symptom Assessment
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D000072670:PTB-Associated Splicing Factor; C452815:IFIH1 protein, human; D000072640:Interferon-Induced Helicase, IFIH1
keywords: Antibody; CADM; MDA5; Myositis; SFPQ; Virus