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Desmosine: an biomarker for elastin degradation

Desmosine and isodesmosine are amino acids that are only present in crosslinked elastin fibers. Levels of desmosines in biofluids therefore specifically reflect the rate of mature elastin degradation.

The process of elastin fiber development consists of several sequential steps. It starts with the synthesis of elastin’s precursor tropo-elastin by various cells. Tropo-elastin proteins are subsequently excreted in the extracellular matrix, aligned with other tropo-elastin monomers into polymers and incorporated in a microfibrillar scaffold. In the final step of elastogenesis, tropo-elastin polymers are crosslinked with each other by the enzyme lysyl oxidase. The elastin-specific amino acids desmosine and isodesmosine are formed during this crosslinking process.

Elastin fibers can be degraded by proteases (e.g. neutrophil elastase), which can be prevented by antiproteases (e.g. alpha-1 antitrypsin). The rate of elastin degradation depends on the balance between protease and antiprotease activity. Desmosines can be liberated from elastin fibers by proteases and measured in various biofluids. The rate of systemic elastin degradation is quantified by measuring desmosines in blood or urine, whereas desmosines levels in sputum and brochoalveolar lavage fluid specifically reflect the rate of pulmonary elastinolysis. Desmosines can also be determined in dynamic tissues, such as lungs, skin, arteries, uterus and tendons. Since desmosines are not species specific, assaying desmosines can be performed on both human and animal samples.

for measuring desmosine in biological specimens

Desmosines can be used to quantify the rate of elastin degradation and thereby disease activity in various diseases, such as COPD, cystic fibrosis and alpha-1 antitrypsin deficiency.

Desmosines levels are inversely related to survival in COPD and CF. They can also be used to monitor efficiency of disease modifying therapies, such as alpha-1 antitrypsin augmentation therapy.

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) is the standard method for measuring desmosines in biological specimens

Many methods have been employed for detection and quantification of desmosine, including high-performance liquid chromatography (HPLC),
radioimmunoassay, ELISA, capillary electrophoresis, and mass spectrometry (LC-MS(/MS)). Among these methodologies, reported
results show that LC-MS/MS gives the greatest selectivity and sensitivity for measurement of desmosine in biological samples.

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