%0 Journal Article
%T Soluble RAGE: a hot new biomarker for the hot joint?
%A Bernhard Moser
%A Barry I Hudson
%A Ann Schmidt
%J Arthritis Research & Therapy
%D 2005
%I BioMed Central
%R 10.1186/ar1764
%X In this issue of Arthritis Research & Therapy, Pullerits and colleagues [1] reported that plasma levels of soluble receptor for advanced glycation endproducts (sRAGE) were decreased in human subjects with rheumatoid arthritis (RA) compared to healthy normal subjects or subjects with non-inflammatory diseases of the joints (NID). Although no significant differences were observed between levels of synovial sRAGE in subjects with RA and NID, synovial sRAGE levels significantly distinguished those RA subjects treated with disease-modifying anti-rheumatic drugs (DMARDs) from those not on these treatments. Subjects with RA receiving methotrexate displayed significantly higher levels of synovial sRAGE [1]. These fascinating findings, based on a single observation point in each subject, prompt us to consider whether sRAGE's role is cause and/or effect in disease/disease activity in the RA joint.In this context, full interpretation of these findings will require comprehensive answers to the questions such as the following: Do plasma sRAGE levels vary from day to day in a subject? Do they vary over the lifespan of the individual? What were the levels of sRAGE in the RA subjects before the onset of disease manifestation? What other environmental or genetic factors might influence levels of sRAGE in the individual subject? Despite these caveats, a key lesson in these studies is that levels of sRAGE, at least in the synovial fluid, might be modified by intense anti-inflammatory therapy. Indeed, an emerging theme in the biology of RAGE links this receptor to proinflammatory mechanisms. At least four classes of inflammatory ligands, namely S100/calgranulins, amphoterin (also known as high mobility group box I or HMGB1), Mac-1, and advanced glycation endproducts (AGEs), are signal transduction ligands of RAGE [2-5]. Intriguingly, these ligand families are upregulated in the serum, the synovium or the fluid bathing the arthritic joint. In certain cases, levels of S100/calgranulins a
%U http://arthritis-research.com/content/7/4/142