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Desmosine as a biomarker of elastin degradation in COPD: current status and future directions

For affiliations, please see the Acknowledgements section.

CORRESPONDENCE: M. Luisetti, Laboratorio di Biochimica e Genetica, Clinica di Malattie dell’Apparato Respiratorio, Fondazione IRCCS Policlinico San Matteo, Università di Pavia, Piazza Golgi 19, 27100 Pavia, Italy. Fax: 39 0382422267. E-mail: m.luisetti{at}smatteo.pv.it

Keywords: Body fluids, capillary electrophoresis, elastin peptides, HPLC, laser-induced fluorescence, mass spectrometry

Received: December 23, 2007
Accepted June 8, 2008

Desmosine (DES) and isodesmosine (IDES) are two unusual, tetrafunctional, pyridinium ring-containing amino acids involved in elastin cross-linking. Being amino acids unique to mature, cross-linked elastin, they are useful for discriminating peptides derived from elastin breakdown from precursor elastin peptides. According to these features, DES and IDES have been extensively discussed as potentially attractive indicators of elevated lung elastic fibre turnover and markers of the effectiveness of agents with the potential to reduce elastin breakdown. In the present manuscript, immunology-based and separation methods for the evaluation of DES and IDES are discussed, along with studies reporting increased levels of urine excretion in chronic obstructive pulmonary disease (COPD) patients with and without ₁-antitrypsin deficiency. The results of the application of DES and IDES as surrogate end-points in early clinical trials in COPD are also reported. Finally, recent advances in detection techniques, including liquid chromatography tandem mass spectrometry and high-performance capillary electrophoresis with laser-induced fluorescence, are discussed. These techniques allow detection of DES and IDES at very low concentration in body fluids other than urine, such as plasma or sputum, and will help the understanding of whether DES and IDES are potentially useful in monitoring therapeutic intervention in COPD.