Circulating Soluble Receptor for Advanced Glycation End Products (sRAGE) as a Biomarker of Emphysema and the RAGE Axis in the Lung

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease that has been traditionally characterized by incompletely reversible airflow limitation. Yet, the latter is poorly correlated with many other clinically relevant characteristics of the disease. Thus, the identification of biomarkers to more accurately assess this heterogeneity and disease severity may facilitate the discovery and development of new treatments and better management of patients with COPD. One molecule that has attracted attention as a potentially useful biomarker specifically for the emphysema subpopulation is the soluble receptor for advanced glycation end products (sRAGE). As the soluble isoform of a key proinflammatory signaling receptor, sRAGE acts as a "decoy" for RAGE ligands and prevents their interaction with the receptor. Multiple reports have now linked sRAGE to COPD, and more specifically to emphysema, and evidence is accumulating that this link is likely mechanistic in nature. Here we review the current state of knowledge about sRAGE biology, the mechanistic links to COPD, and the evidence for using it as a biomarker for emphysema. We also discuss sRAGE as a potential target for therapeutic intervention in COPD.