Antitrypsin

Antitrypsin, commonly called alpha-1 antitrypsin (AAT), is a glycoprotein in the serpin family that functions as a protease inhibitor. It primarily inhibits neutrophil elastase but can target other proteases. It is produced mainly by hepatocytes and released into the bloodstream, with important presence in the lungs where it protects tissue from proteolytic damage.

In the lungs, AAT protects elastin and other extracellular matrix components from degradation by activated neutrophils. Deficiency leads to insufficient inhibition of elastase, promoting inflammation and destruction of alveolar walls. This can result in early-onset panacinar emphysema, particularly in the lower lung zones. Severe deficiency variants may also cause liver disease due to accumulation of misfolded AAT within hepatocytes.

Genetics and forms: The SERPINA1 gene on chromosome 14 encodes AAT. Common alleles include M (normal), S, and Z. PiZZ and other defective or null alleles produce low circulating AAT levels and higher risk of lung disease; PiZ is associated with severe deficiency, while PiSZ and PiMZ confer intermediate risk. The condition is more prevalent among people of Northern European ancestry.

Diagnosis and management: Suspect AAT deficiency in adults with unusually early or unexplained emphysema or liver disease, especially without typical risk factors. Diagnosis uses serum AAT levels, followed by phenotype and/or genotype testing, along with lung function testing. Management emphasizes avoidance of lung irritants (notably smoking), vaccination, and standard COPD therapies. Augmentation therapy with pooled human AAT can slow progression in those with severe deficiency and established emphysema. In advanced cases, liver transplantation may be considered; research into gene therapy and other treatments is ongoing.