Rheumatology Advance Access published online on June 19, 2009
Rheumatology, doi:10.1093/rheumatology/kep151
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Expression of advanced glycation end products and their receptor in skin from patients with systemic sclerosis with and without calcinosis
1Tissue Injury and Repair Research Group, Research School of Clinical and Laboratory Sciences, 2Rheumatic Diseases Centre, 3Dermatology Centre, Hope Hospital and 4Epidemiology Research Group, School of Translational Medicine, The University of Manchester, Manchester, UK.
Correspondence to:
Christine A. Davies, Tissue Injury and Repair Research Group, Research School of Clinical and Laboratory Sciences, Manchester Academic Health Science Centre, The University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK. E-mail: christine.a.davies{at}manchester.ac.uk
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Abstract |
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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
-(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-(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.
KEY WORDS: Advanced glycation end products, Systemic sclerosis, Calcinosis, Immunohistochemistry, Skin
Submitted 24 September 2008;
revised version accepted 13 May 2009.
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