Abstract
The receptor for advanced glycation endproducts (RAGE) interacts with distinct ligand families linked to the inflammatory response. Studies in animal models suggest that RAGE is upregulated in the inflamed joint and that blockade of the receptor, using a ligand decoy soluble form of RAGE (sRAGE), attenuates joint inflammation and expression of inflammatory and tissue-destructive mediators. In this issue of Arthritis Research & Therapy, Rille Pullerits and colleagues reported that plasma levels of sRAGE were reduced in subjects with rheumatoid arthritis compared with healthy controls or subjects with non-inflammatory joint disease. These findings suggest the possibility that levels of sRAGE might be a biomarker of inflammation. Not resolved by these studies, however, is the intriguing possibility that endogenously higher levels of sRAGE might be linked to a lower incidence of arthritis or to the extent of inflammation. Nevertheless, although 'cause or effect' relationships may not be established in this report, fascinating insights into RAGE, inflammation and human arthritis emerge from these studies.
Highlights
In this issue of Arthritis Research & Therapy, Pullerits and colleagues [1] reported that plasma levels of soluble receptor for advanced glycation endproducts were decreased in human subjects with rheumatoid arthritis (RA) compared to healthy normal subjects or subjects with noninflammatory diseases of the joints (NID)
No significant differences were observed between levels of synovial soluble receptor for advanced glycation endproducts (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. 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
Summary
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 noninflammatory diseases of the joints (NID). 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. In the specific context of arthritis, administration of soluble RAGE to mice with collagen-induced arthritis attenuated clinical scores of joint inflammation, in parallel with
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