Skin autofluorescence is increased in systemic lupus erythematosus but is not reflected by elevated plasma levels of advanced glycation endproducts.
OBJECTIVE
To examine whether skin advanced glycation endproducts (AGEs) accumulation, plasma levels of AGEs-N(epsilon)-carboxymethyllysine (CML) and N(epsilon)-carboxyethyllysine (CEL)-and serum levels of soluble receptor for AGEs (sRAGE) are elevated in SLE patients compared with controls, and whether these parameters are related to disease activity and endothelial cell (EC) activation.


METHODS
Ten SLE patients (9 women, age 34 +/- 13 yrs, mean +/- s.d.) and 10 age- and sex-matched controls were included. Patients were analysed during inactive as well as active disease. Skin AGE accumulation was estimated using ultraviolet-A (UV-A) light for measurement of autofluorescence obtained by Excitation-Emission matrix Scanner (AF-EEMS). Levels of CML and CEL were determined by tandem mass spectrometry. Levels of sRAGE and of soluble vascular cell adhesion molecule-1 (sVCAM-1) were determined by ELISAs.


RESULTS
Skin AF-EEMS was increased in SLE patients compared with controls (P < 0.05). Levels of CML and CEL were comparable between patients and controls and were not influenced by disease activity. sRAGE and sVCAM-1 levels were higher in quiescent SLE patients compared with controls (P < 0.05) and increased further during active disease (P < 0.05). In patients with quiescent disease and controls, sRAGE levels correlated to sVCAM-1 levels (r = 0.579, P = 0.007).


CONCLUSIONS
Skin AGEs and levels of sRAGE and sVCAM-1 were elevated in SLE patients, whereas levels of CML and CEL were comparable with controls. As sRAGE even further increased during endothelial activation, it might be hypothesized that sRAGE acts as a decoy receptor. Why this proposed mechanism is insufficient to prevent increased AGE accumulation in the skin of SLE patients has to be established.
Nienhuis
H L
HL
Division of Rheumatology and Clinical Immunology, University Medical Center Groningen, The Netherlands. h.l.a.nienhuis@int.umcg.nl
de Leeuw
K
K
Bijzet
J
J
Smit
A
A
Schalkwijk
C G
CG
Graaff
R
R
Kallenberg
C G
CG
Bijl
M
M
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005453:Fluorescence; D017127:Glycation End Products, Advanced / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood; D012720:Severity of Illness Index; D012867:Skin / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D019010:Vascular Cell Adhesion Molecule-1; C054688:N(6)-(1-carboxyethyl)lysine; C048496:N(6)-carboxymethyllysine; D008239:Lysine