Measuring the Concentration of Active Alpha-1 Antitrypsin in Serum

Active Alpha-1 antitrypsin (AAT) circulates in blood in two isoforms in dynamic equilibrium: 1) native AAT, which binds irreversibly to neutrophil elastase, and 2) thiol-modified AAT, which binds reversibly to neutrophil elastase, either of which can be inactivated by oxidation, cleavage, covalent binding, and bound antibodies. Anti-AAT antibodies used for detecting AAT in plasma bind to active and inactive protein, thereby overestimating the concentration of functional protein. Active AAT can be quantitated by measuring its inhibition of active-site titrated elastase. A method for measuring active AAT in the presence of competing proteinase inhibitors in plasma has been developed and is described herein.