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Rheumatology Advance Access published online on August 27, 2006

Rheumatology, doi:10.1093/rheumatology/kel076
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received August 12, 2005
Accepted February 10, 2006

Concise Report

Circulating levels of N{varepsilon}-(carboxymethyl)lysine are increased in systemic sclerosis

O. Kaloudi 1, G. Basta 2, F. Perfetto 1, F. Bartoli 1, A. Del Rosso 1, I. Miniati 1, M. L. Conforti 1, S. Generini 1, S. Guiducci 1, R. Abbate 3, A. Pignone 1, S. Castellani 4, R. Livi 1, R. De Caterina 5, and M. Matucci-Cerinic 1 *

1 Department of Medicine, Division of Rheumatology, University of Florence, Florence, Italy
2 CNR Institute of Clinical Physiology, University of Pisa, Pisa, Italy
3 Departments of Medical and Surgical Critical Care, University of Florence, Florence, Italy
4 Internal Medicine and Cardiology, University of Florence, Florence, Italy
5 CNR Institute of Clinical Physiology, University of Pisa, Pisa, Italy; Institute of Cardiology and Center for Excellence on Aging, ‘G. d'Annunzio’ University, Chieti, Italy

* To whom correspondence should be addressed.
M. Matucci-Cerinic, E-mail: cerinic{at}unifi.it


   Abstract

Objective. Advanced glycation endproducts (AGEs), including N{varepsilon}-(carboxymethyl)lysine-protein adducts (CML) are involved in micro/macrovascular changes and are co-localized with adhesion molecules in inflamed tissues. Serum levels of CML were investigated in systemic sclerosis (SSc) characterized by microvascular modifications and correlated with indices of micro/macrovascular damage.

Methods. In 66 SSc patients (limited SSc, n = 55; diffuse SSc, n = 11) and 20 controls, CML serum levels were measured by enzyme-linked immunosorbent assay. Nailfold capillaroscopy, intima-media thickness (IMT) and the ankle-brachial index (ABI) were also recorded, to characterize micro/macrovascular involvement.

Results. CML levels were significantly higher in SSc (79.2 ± 39 mg/ml vs 49.6 ± 26.1 mg/ml, mean ± s.d.; P<0.01), without significant differences between SSc subsets. CML levels were significantly higher in all capillaroscopic patterns: the ‘early’ pattern showed higher levels than ‘active’ and ‘late’ patterns. IMT was significantly higher in SSc (P<0.01) than in controls, whilst ABI was no different from controls.

Conclusions. These data indicate that although both CML formation and macrovascular involvement are increased in SSc, there is no correlation between these two parameters. However, the characteristic early nailfold capillaroscopy changes of SSc are associated with proportionally greater CML formation, suggesting that AGEs are involved in SSc microangiopathy.

Keywords: Systemic sclerosis; N{epsilon}-(carboxymethyl)lysine (CML); Advanced glycation endproducts.
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