Expression of advanced glycation end products and their receptor in skin from patients with systemic sclerosis with and without calcinosis

Objectives. Our aim was to establish which tissue components express advanced glycation/lipoperoxidation end products (AGEs) and their receptor (RAGE) in skin from patients with SSc, and how their expression relates to the disease subtypes and various clinical parameters. Methods. Skin punch biopsies were taken from the forearms of 61 SSc patients with IcSSc; 32 with calcinosis (IcSScCal) and 29 without IcSSc, 36 with the dcSSc subtype and 22 healthy control subjects. Immunohistochemical localization of AGE-CML [N(epsilon)-(carboxymethyl) lysine] and RAGE was assessed semi-quantitatively on the microvascular endothelium, dermal fibroblasts and the cutaneous extracellular matrix (ECM). The Kruskal-Wallis one-way ANOVA was used to compare data between groups. Results. AGE-CML expression on the papillary dermis ECM of IcSScCal was greater than in the control group (P = 0.016). The reticular dermis of IcSScCal showed increased AGE-N(epsilon)-(carboxymethyl) lysine (CML) expression compared with controls (P = 0.002), dcSSc (P = 0.024) and lcSSc (P = 0.025). Increased immunostaining for RAGE was seen on the reticular dermis ECM of the IcSScCal group compared with controls (P = 0.007). The IcSScCal subgroup showed statistically significant correlations for AGE-CML, and to a lesser extent for RAGE, with increased RP duration. There was no consistent evidence that the expression of AGE-CML or RAGE related to autoantibody status, clinical or histological skin score or patient age. Conclusions. Our results indicate the possible contribution of AGE-CML deposition on the ECM in the dermis of the IcSScCal subgroup to the pathogenesis of formation of calcinotic deposits.