Expression of advanced glycation end products and their receptor in skin from patients with systemic sclerosis with and without calcinosis.
OBJECTIVE
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.
Davies
Christine A
CA
Tissue Injury and Repair Research Group, Research School of Clinical and Laboratory Sciences, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK. christine.a.davies@manchester.ac.uk
Herrick
Ariane L
AL
Cordingley
Lis
L
Freemont
Anthony J
AJ
Jeziorska
Maria
M
D000328:Adult; D000704:Analysis of Variance; D001706:Biopsy; D002114:Calcinosis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D017127:Glycation End Products, Advanced / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis*; D012595:Scleroderma, Systemic / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000737:chemistry* / Q000473:pathology; D018709:Statistics, Nonparametric; D013997:Time Factors
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic