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AB0489 Leucine-Rich Alpha-2 Glycoprotein (LRG) as a Potential Disease Activity Marker During IL-6 Blockade in Autoimmune Arthritis
  1. Y. Takahashi1,
  2. M. Fujimoto1,
  3. S. Serada1,
  4. A. Ogata2,
  5. T. Nanki3,
  6. K. Hattori4,
  7. T. Takeuchi5,
  8. T. Naka1
  1. 1Laboratory for Immne Signal, National institute of biomedical innovation, Ibaraki
  2. 2Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Suita
  3. 3Department of Clinical Research Medicine, Teikyo University, Itabashi, Tokyo
  4. 4Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical, Gotemba
  5. 5Department of Internal Medicine, Division of Rheumatology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan


Background C-reactive protein (CRP) is frequently used to evaluate inflammation in patients with rheumatoid arthritis (RA). However, CRP is normalized when IL-6 function is potently suppressed by anti-cytokine biologics such as tocilizumab. Therefore, there is growing need for a new biomarker that can detect RA disease activity during this therapy. By proteomic screening of sera from patients with RA, we previously identified serum leucine-rich alpha-2 glycoprotein (LRG) as a potential biomarker that reflects disease activity in RA better than CRP.

Objectives The object of this study is to investigate the clinical significance of LRG as a biomarker of RA disease activity during anti-IL6 biologic therapy.

Methods As a preclinical testing, cynpmolgus monkeys with collagen induced arthritis (CIA) were treated with anti-IL-6 receptor antibody (anti-IL-6-R mAb) and joint sewelling and rigidity were scored for clinical assessment of arthritis throughout the experiment. At the time of sacrifice, blood samples were collected and serum LRG and CRP levels were evaluated.

Results In CIA monkeys with anti-IL-6R mAb treatment, plasma LRG levels correlated better with disease activity than plasma CRP levels, presumably due to the fact that LRG levels were elevated in some animals with negative CRP in spite of high arthritis scores. Furthermore, among tocilizumab-treated patients for 6months with normalized CRP levels, serum LRG levels were significantly higher in patients with active RA (defined by CDAI>2.8) than those with RA in remission (CDAI≤2.8).

Conclusions Our study indicates that LRG is more useful biomarker for discriminating active diseases in RA, even when CRP levels are reduced or normalized under IL-6 suppression.


  1. Navarro-Millán I, et al. Systematic Review of Tocilizumab for Rheumatoid Arthritis: A New Biologic Agent Targeting the Interleukin-6 Receptor Receptor Clin Ther 2012; 788-802

Disclosure of Interest None declared

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