RAGE against arthritis

RAGE (receptor for advanced glycation end-products) and its proinflammatory ligands are commonly identified in the joints of patients with rheumatoid arthritis (RA), but their role in the disease has been unclear. In May Genes and Immunity, Hofmann and colleagues from Columbia University, New York, show that a polymorphism in the RAGE gene within the ligand-binding domain of the receptor (RAGE 82S) may contribute to enhanced proinflammatory mechanisms in immune/inflammatory diseases (Genes Immun 2002, 3:123-135).

Hofmann et al. used a murine model of arthritis and observed that blockade of RAGE suppressed clinical and histologic evidence of arthritis and diminished levels of proinflammatory cytokines in affected tissues. But, cells bearing the RAGE 82S allele displayed enhanced binding and cytokine/MMP generation following ligation by a prototypic S100/calgranulin compared with cells expressing the RAGE 82G allele. In addition, in human subjects, a case-control study demonstrated an increased prevalence of the 82S allele in patients ...