Evaluating disease activities of rheumatoid arthritis by a new inflammatory biomarker

Abstract

  Inflammatory biomarkers are useful as objective and quantitative indicators of disease activity in rheumatic diseases. The most representative biomarker is CRP, which is an acute phase protein produced in liver during inflammation, and its upregulation is absolutely dependent on stimulation by the cytokine IL-6. Recently, biological agents that target IL-6 signaling have been developed, and CRP often fails to detect disease activity and/or concomitant infection, given that CRP elevation requires intact IL-6 signaling. Thus, a search for new inflammatory biomarkers is warranted. Previously, we performed a proteomics analysis and identified the elevation of leucine-rich α2 glycoprotein（LRG）in sera from patients with rheumatoid arthritis. Similar to CRP, LRG has properties of acute phase proteins upregulated in the liver in response to inflammatory cytokine stimulation. Nevertheless, LRG is induced not only by IL-6 but also by others such as IL-1β, TNF-α and IL-22, and its expression is detectable not only in the liver but also at inflammatory lesions, indicating that LRG has characteristics different from CRP. We have found that LRG is more useful than CRP in evaluating disease activity of rheumatoid arthritis during tocilizumab therapy and ulcerative colitis. As a result of the collaboration with a company, an LRG measurement system for clinical use has already been developed. LRG may be applicable in the near future to an objective and quantitative indicator of disease activity in rheumatic diseases.