COMPARISON OF ALPHA-1-ANTITRYPSIN LEVELS AND ANTINEUTROPHIL ELASTASE CAPACITY OF BLOOD AND LUNG IN A PATIENT WITH THE ALPHA-1-ANTITRYPSIN PHENOTYPE NULL-NULL BEFORE AND DURING ALPHA-1-ANTITRYPSIN AUGMENTATION THERAPY

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Abstract
The null-null phenotype of .alpha.1-antitrypsin (.alpha.1AT), a phenotype characterized by no detectable .alpha.1AT in serum, presents a rare opportunity to examine the contribution of .alpha.1AT to the antineutrophil elastase protection of the lower respiratory tract. The subject, a 35-yr-old lifetime nonsmoker with moderate emphysema, has been characterized as having .alpha.1AT serum levels of zero resulting from the homozygous inheritance of .alpha.1AT genes that do not express detectable .alpha.1AT mRNA transcripts. Evaluation of the antineutrophil elastase capacity of the null-null serum showed it was < 5% of normal, whereas that of the epithelial lining fluid (ELF) of the lower respiratory tract was 13% of normal. However, after 60 mg/kg of intravenously administered .alpha.1AT augmentation therapy once weekly for 4 wk, the serum .alpha.1AT levels peaked at > 300 mg/dl, trough levels just prior to the next infusion were 81 .+-. 2 mg/dl, and the average serum level integrated for the month of infusions was 138 mg/dl. Consistent with this serum rise in .alpha.1AT, the serum antineutrophil elastase capacity increased in parallel (r = 0.98). Importantly, evaluation of the ELF 2 and 6 days after infusion demonstrated increases of .alpha.1AT levels (range 1.4 to 2.1 .mu.M) and antineutrophil elastase capacity (range, 1.6 to 2.5 .mu.M), values within the lower range of normal. Furthermore, the lung ELF .alpha.1AT levels rose in direct proportion to the serum .alpha.1AT levels, and the ELF antineutrophil elastase capacity rose in direct proportion to the ELF .alpha.1AT levels. Taken together, these findings demonstrate that .alpha.1AT provides > 85% of the antineutrophil elastase protection for the lower respiratory tract and that this protection can be modulated by the blood levels of .alpha.1AT.