A new method of measuring the levels of alpha-1 antitrypsin (AAT) activity in a sensitive and specific manner was discovered, as published in the Journal of Pharmaceutical and Biomedical Analysis.

“The data obtained demonstrated the ECFISA [elastase complex formation immunosorbent assay] as an accurate, precise, selective, and very sensitive method for AAT activity measurement at low levels previously inaccessible for direct measurement,” the researchers said.

It is important to be able to measure even low levels of AAT to refine AAT augmentation therapy, a targeted AAT deficiency (AATD) treatment that aims to raise the serum concentration of AAT to protective levels. The current study aimed to develop a more sensitive method of measuring functional AAT levels than the ones currently available.

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ECFISA uses proteolytically active elastase, which is bound to a plate. This elastase attacks functionally active AAT by forming a stable complex. An antiAAT peroxidase conjugate is then used to detect and measure this complex.

Read more about AATD therapies

To confirm that the assay only detects functionally active AAT, the researchers used 3 different approaches to inactivate AAT: heating, oxidation, and complex formation with elastase.

“We confirmed beyond doubt that the ECFISA exclusively measures functionally active AAT and that these measurements are unimpaired by the presence of high concentrations of functionally inactive AAT,” the researchers wrote.

AATD is a rare genetic disease characterized by low levels of functional AAT in the body. The role of AAT is to inhibit the neutrophil elastase protease, which participates in the phagocytosis of frequently inhaled airborne particles that become trapped in the lungs, as part of the immune response.

However, in the absence of AAT, neutrophil elastase protease also attacks healthy lung tissue. AAT levels below 20 µM mean that the lungs are unprotected and prone to damage. AAT replacement therapy aims to increase the levels of AAT in the plasma to reach at least 11 µM, though this threshold is currently debated.


Engelmaier A, Weber A. Sensitive and specific measurement of alpha1-antitrypsin activity with an elastase complex formation immunosorbent assay (ECFISA). J Pharm Biomed Anal. 2022;209(5):114476. doi:10.1016/j.jpba.2021.114476