Leucine-Rich Alpha-2 Glycoprotein Is a Potential Disease Activity Marker Under IL-6 Suppression in Autoimmune Arthritis

Yusuke Takahashi¹, Minoru Fujimoto², Satoshi Serada³ and Tetsuji Naka², ¹a doctoral student, Osaka university, Suita city, Japan, ²Laboratory for immune signal, National Institute of Biomedical Innovation, Ibaraki, Japan, ³7-6-8, Saito-asagi, National Institute of Biomedical Innovation, Laboratory for immune signal, Japan, Ibaraki, Japan

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: C Reactive Protein, cytokines, IL-6R signaling, Laboratory tests and tocilizumab

Session Information

Title: Rheumatoid Arthritis - Animal Models

Session Type: Abstract Submissions (ACR)

Background/Purpose

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, novel biomarkers are required for accurate and sensitive assessment of the inflammation during anti-cytokine therapy. By proteomic screening of sera from patients with rheumatoid arthritis (RA), we previously identified serum leucine-rich alpha-2 glycoprotein (LRG)as a potential biomarker that reflects disease activity in RA better than CRP.

This study is aimed to investigate the clinical significance of LRG as a biomarker of RA disease activity during anti-IL6 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 to be subjected to the measurement LRG and CRP 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 (<0.2mg/dL), serum LRG levels were significantly higher in patients with active RA (defined by CDAI>10) than those with RA with low disease activity (CDAI≤10).

Conclusion

Our study indicates that LRG is a promising biomarker for monitoring disease activity in RA, even when CRP levels are reduced or normalized by anti-cytokine therapy.

Disclosure:

Y. Takahashi,
None;

M. Fujimoto,
None;

S. Serada,
None;

T. Naka,
None.

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