There are 2 million individuals in the U.S.A. with emphysema. Two percent develop the disease because of inheritance of a deficiency of alpha 1-antitrypsin (AAT), an antiprotease that protects the lower respiratory tract from destruction mediated by elastase released by neutrophils. Cloning, sequencing and oligionucleotides have been used to detect specific mutations in the AAT gene. The """"""""null"""""""" AAT state is associated with an intact gene but no detectable AAT mRNA. Alvelar macrophages produce AAT, thus providing the protein at the site of disease. Site directed mutagenesis has been used to produce a recombinant AAT molecules in E. coli that is oxidation resistant. Therapy of AAT deficiency with AAT purified from pooled plasma has demonstrated that the anti-neutrophil-elastase defenses of the lung can be reestablished with intermittent intravenous administration of 60 mg/kg AAT.
