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 lcSSc; 32 with calcinosis (lcSScCal) and 29 without lcSSc, 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 lcSScCal was greater than in the control group (P = 0.016). The reticular dermis of lcSScCal 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 lcSScCal group compared with controls (P = 0.007). The lcSScCal 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 lcSScCal subgroup to the pathogenesis of formation of calcinotic deposits.
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 lcSSc; 32 with calcinosis (lcSScCal) and 29 without lcSSc, 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 lcSScCal was greater than in the control group (P = 0.016). The reticular dermis of lcSScCal 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 lcSScCal group compared with controls (P = 0.007). The lcSScCal 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 lcSScCal subgroup to the pathogenesis of formation of calcinotic deposits.
Authors: María Pilar Cruz-Domínguez; Grettel García-Collinot; Miguel A Saavedra; Gabriela Medina; Rosa Angélica Carranza-Muleiro; Olga Lidia Vera-Lastra; Luis J Jara Journal: Clin Rheumatol Date: 2016-10-07 Impact factor: 2.980
Authors: Graham Dinsdale; Sarah Wilkinson; Jack Wilkinson; Tonia L Moore; Joanne B Manning; Michael Berks; Elizabeth Marjanovic; Mark Dickinson; Ariane L Herrick; Andrea K Murray Journal: Microvasc Res Date: 2020-04-19 Impact factor: 3.514