URINARY-EXCRETION OF DESMOSINE (ELASTIN CROSS-LINKS) IN SUBJECTS WITH PIZZ ALPHA-1-ANTITRYPSIN DEFICIENCY, A PHENOTYPE ASSOCIATED WITH HEREDITARY PREDISPOSITION TO PULMONARY-EMPHYSEMA

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Abstract
To evaluate the concept that lung elastin degradation is accelerated in homozygous alpha-1-antitrypsin (AAT) deficient persons, we prepared acid hydrolysates of urine and used a radioimmunoassay for desmosine to measure urine concentrations of this elastin-specific cross-link in such persons and in control subjects. Excretion of desmosine in 17 homozygous AAT-deficient (PiZZ) patients with emphysema was compared with that in 27 patients with interstitial lung diseases (16 sarcoid, 5 idiopathic pulmonary fibrosis, 6 other interstitial lung diseases) and 26 healthy subjects. Both smokers and nonsmokers were present in all groups. Urinary desmosine concentration (.mu.g/100 mg creatinine) was 2.35 .+-. 0.93 in the PiZZ patients, 2.49 .+-. 1.01 in those with interstitial lung disease, and 2.05 .+-. 0.54 in the healthy control subjects (p > 0.1, all comparisons). Because abnormal pulmonary elastolysis may be largely completed before symptoms of emphysema develop in AAT-deficient persons, we also tested 6 asymptomatic adults with homozygous AAT deficiency (PiZZ) and 5 PiZZ children. Urine desmosine (.mu.g/100 mg creatine) was not significantly elevated in either group compared with that in the age-matched control subjects, although children (PiZZ and age-matched controls) showed higher excretions than did adults (6 asymptomatic PiZZ adults, 2.60 .+-. 0.91; 5 PiZZ children, 3.27 .+-. 0.62; 10 control children, 3.61 .+-. 0.62). These data suggest that pathologic lung elastolysis in the PiZZ subject may constitute too small a fraction of total-body elastin turnover to be detected by this method. Alternatively, it is possible that lung elastin degradation may occur episodically rather than continuously and thus not be detectable when these patients are clinically stable.