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iTRAQ-based proteomic identification of leucine rich alpha 2 glycoprotein (LRG) 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. 1 Laboratory for Immune Signal, National Institute of Biomedical Innovation, Japan;
  2. 2 Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University, Japan;
  3. 3 Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan;
  4. 4 Healthcare center, Osaka University Graduate School of Medicine, Japan;
  5. 5 Department of Ophthalmology, Osaka University Medical School, Osaka, Japan;
  6. 6 Laboratory of Immune Regulation, Osaka University Graduate School of Frontier Biosciences, Japan
  1. Correspondence to: Tetsuji Naka, Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7-6-8, Saito-Asagi, Ibaraki city, Osaka, 567-0085, Japan; tnaka{at}nibio.go.jp

Abstract

Objective: To identify a novel serum biomarker of disease activity in inflammatory autoimmune disorders using a quantitative proteomic approach.

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

Results: Of 326 proteins identified by proteomic analysis, we identified increased serum levels of leucine rich alpha 2 glycoprotein (LRG) in RA patients before therapy. ELISA analysis revealed that serum LRG concentrations were significantly elevated in RA patients compared to healthy controls and decreased after anti-TNF therapy. Serum LRG concentrations correlated with serum C-reactive protein (CRP) levels in patients with RA, Behcet’s disease and Crohn’s disease (CD) and correlated with disease activity in RA and CD. Interestingly, in a subpopulation of active CD patients with normal CRP levels, serum LRG concentrations were elevated. Furthermore, serum LRG concentrations were significantly higher in CD patients refractory to anti-TNF therapy compared to those responsive to this therapy.

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. Therefore, serum LRG potentially surrogate for CRP.

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