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iTRAQ-based proteomic identification of leucine-rich α-2 glycoprotein as a novel inflammatory biomarker in autoimmune diseases
  1. Satoshi Serada1,
  2. Minoru Fujimoto1,
  3. Atsushi Ogata2,
  4. Fumitaka Terabe3,
  5. Toru Hirano2,
  6. Hideki Iijima3,
  7. Shinichiro Shinzaki3,
  8. Teppei Nishikawa4,
  9. Tomoharu Ohkawara1,
  10. Kota Iwahori1,
  11. Nobuyuki Ohguro5,
  12. Tadamitsu Kishimoto6,
  13. Tetsuji Naka1
  1. 1Laboratory for Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan
  2. 2Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
  3. 3Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
  4. 4Healthcare Centre, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
  5. 5Department of Ophthalmology, Osaka University Medical School, Suita, Osaka, Japan
  6. 6Laboratory of Immune Regulation, Osaka University Graduate School of Frontier Biosciences, Suita, Osaka, Japan
  1. Correspondence to Dr Tetsuji Naka, Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7-6-8, Saito-asagi, Ibaragi, Osaka 567-0085, Japan; tnaka{at}


Objective To identify a novel serum biomarker of disease activity in inflammatory autoimmune disorders.

Methods Sera obtained from rheumatoid arthritis (RA) patients before and after anti-TNF therapy were analysed by iTRAQ (isobaric tags for relative and absolute quantitation) quantitative proteomic analysis and further validated by ELISA.

Results Of 326 proteins identified by proteomic analysis, increased serum levels of leucine-rich α-2 glycoprotein (LRG) was identified in RA patients before therapy. Serum LRG concentrations were significantly elevated in RA patients compared with healthy controls and decreased after anti-TNF therapy. Furthermore, serum LRG concentrations correlated with disease activity in RA and Crohn's disease (CD). Interestingly, in a subpopulation of patients with active CD and normal C-reactive protein levels, serum LRG concentrations were elevated.

Conclusions LRG represents a novel serum biomarker for monitoring disease activity during therapy in autoimmune patients, particularly useful in patients with active disease but normal CRP levels.

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  • Funding This study was supported by a grant-in-aid for challenging exploratory research (21659246) and by the Ministry of Health, Labour and Welfare of Japan.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Osaka University and National Institute of Biomedical Innovation.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.