Western Society of Allergy, Asthma and Immunology (WSAAI), 2025
Annual scientific session uniting allergists, immunologists, nurses, and physician assistants aimed at maintaining the highest standard of practice in allergy care.
Pathophysiology
AATD is caused by a mutation in the SERPINA1 gene on chromosome 14 encoding for A1PI.6 Each person has two alleles (variants) of the gene, one inherited from each parent where the most common ones are:5
- M allele— results in normal levels of functional A1PI6,7
- S allele— expresses approximately 50 to 60% normal A1PI where the variant is unstable and easily degrades8,9
- Z allele— expresses approximately 10 to 20% of normal A1PI due to much of the A1PI accumulating in the liver8,9
A1PI is primarily synthesized in the liver and secreted into the bloodstream where it diffuses into the lungs and other tissues.2,8,10 The main role of A1PI is to inhibit neutrophil elastase (NE) and keep its activity in check.2,10 NE is a proteinase responsible for the breakdown of a variety of proteins involved in modulating inflammation and therefore plays a key role in tissue repair and protection from infections.11 Therefore, a deficiency in functional A1PI results in excessive NE activity and leads to the degradation of lung tissue and blood vessels.12
