Concise report

iTRAQ-based proteomic identification of leucine rich alpha 2 glycoprotein (LRG) as a novel inflammatory biomarker in autoimmune diseases

Satoshi Serada¹, Minoru Fujimoto¹, Atsushi Ogata², Fumitaka Terabe³, Toru Hirano², Hideki Iijima³, Shinichiro Shinzaki³, Teppei Nishikawa⁴, Tomoharu Ohkawara¹, Kota Iwahori¹, Nobuyuki Ohguro⁵, Tadamitsu Kishimoto⁶, Tetsuji Naka^1,*

¹ Laboratory for Immune Signal, National Institute of Biomedical Innovation, Japan;
² Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University, Japan;
³ Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan;
⁴ Healthcare center, Osaka University Graduate School of Medicine, Japan;
⁵ Department of Ophthalmology, Osaka University Medical School, Osaka, Japan;
⁶ Laboratory of Immune Regulation, Osaka University Graduate School of Frontier Biosciences, Japan

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

Accepted 3 October 2009

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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