Circulating levels of N-epsilon-(carboxymethyl)lysine are increased in systemic sclerosis

Objective. Advanced glycation endproducts (AGEs), including N-epsilon-(carboxymethyl)lysine-protein adducts (CML) are involved in micro/macrovascular changes and are co-localized with adhesion molecules in inflamed tissues. Serum levels of CML were investigated in systemic sclerosis (SSc) characterized by microvascular modifications and correlated with indices of micro/macrovascular damage. Methods. In 66 SSc patients (limited SSc, n=55; diffuse SSc, n=11) and 20 controls, CML serum levels were measured by enzyme-linked immunosorbent assay. Nailfold capillaroscopy, intima-media thickness (IMT) and the ankle-brachial index (ABI) were also recorded, to characterize micro/macrovascular involvement. Results. CML levels were significantly higher in SSc (79.2±39 micron mg/ml vs 49.6±26.1 micron mg/ml, mean±S.D.; P0.01), without significant differences between SSc subsets. CML levels were significantly higher in all capillaroscopic patterns: the 'early' pattern showed higher levels than 'active' and 'late' patterns. IMT was significantly higher in SSc (P0.01) than in controls, whilst ABI was no different from controls. Conclusions. These data indicate that although both CML formation and macrovascular involvement are increased in SSc, there is no correlation between these two parameters. However, the characteristic early nailfold capillaroscopy changes of SSc are associated with proportionally greater CML formation, suggesting that AGEs are involved in SSc microangiopathy.