title: Preliminary evidence that augmentation therapy diminishes degradation of cross-linked elastin in alpha-1-antitrypsin-deficient humans.
abstract: It is hypothesized that emphysema develops in some severely alpha 1-antitrypsin (AAT)-deficient persons because endogenous elastases are not adequately controlled by AAT, and accelerated elastin degradation occurs. It is not known whether augmentation therapy with AAT diminishes degradation of lung elastin in severely deficient persons with lung disease. Two severely deficient, PiZ patients were studied, a 63-year-old never-smoking woman with bronchiectasis and a 41-year-old smoking man with emphysema. Urinary desmosine (DES) was determined before and after augmentation therapy with AAT, 260 mg/kg/month. Mean +/- SEM pretreatment urinary DES was elevated in both patients, 19.7 +/- 0.9 (n = 2) and 10.8 +/- 0.2 (n = 2) micrograms/g creatinine, respectively, compared to normal values of 7.5 +/- 0.3 (n = 22) micrograms/g creatinine. Following augmentation therapy, urinary DES values decreased 40 and 36%, respectively, to 11.9 +/- 0.3 (n = 8) and 6.9 +/- 0.4 (n = 7) microgram/g creatinine (p < 0.05). We conclude that monthly AAT augmentation therapy decreased DES excretion in the urine of these PiZ patients. We speculate that since there was lung disease in both patients, a decrease in degradation of lung elastin is the most likely explanation for this observation.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, MA 02118, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Stone
authors.forename: T A
authors.initials: TA
authors.lastname: Morris
authors.forename: C
authors.initials: C
authors.lastname: Franzblau
authors.forename: G L
authors.initials: GL
authors.lastname: Snider
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000652:urine; D001987:Bronchiectasis / Q000378:metabolism* / Q000628:therapy*; D003895:Desmosine / Q000652:urine; D004549:Elastin / Q000378:metabolism*; D004646:Emphysema / Q000378:metabolism* / Q000628:therapy*; D005260:Female; D006801:Humans; D007524:Isodesmosine / Q000652:urine; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000009:adverse effects; D000515:alpha 1-Antitrypsin / Q000627:therapeutic use*; D019896:alpha 1-Antitrypsin Deficiency
chemical_list: D000596:Amino Acids; D000515:alpha 1-Antitrypsin; D003895:Desmosine; C015484:pyridinoline; D004549:Elastin; D007524:Isodesmosine