Spanish researchers have found that circulating polymers (CP) of alpha-1 antitrypsin (AAT) may play a role in the mechanisms of alpha-1 antitrypsin deficiency (AATD). This could help physicians identify AATD patients who are at a higher risk of developing lung and liver disease, according to a study published in Respiratory Research. 

AATD is a rare disease characterized by a deficiency in the AAT protein, which is caused by its misfolding and polymerization within hepatocytes. The most prominent features of AATD are lung disease (ie, emphysema), followed by liver disease (ie, hepatitis and cirrhosis). 

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Researchers have known that CP of AAT are present in patients with AATD. However, little is known about the exact role they play in the pathogenesis of both lung and liver disease in AATD patients. Researchers therefore decided to investigate any possible association between CP and disease progression in AATD.

This was a cross-sectional study conducted at a Spanish reference center for AATD, the Vall d’Hebron Hospital Campus in Barcelona. A total of 70 AATD patients of various genotypes with moderate to severe AAT deficiency were included in the study.

Researchers first quantified the levels of AAT in each patient, then quantified the levels of CP in each patient by performing a sandwich enzyme-linked immunosorbent assay with plasma samples using the 2C1 monoclonal antibody against AAT polymers. Through this method, researchers were able to determine the proportion of polymers vs the total levels of AAT (%), as well as the total polymer concentrations (µg/mL).

The results showed that genotype Pi*ZZ patients had the highest concentrations of CP, while patients with genotypes Pi*SS and Pi*SI, as well as the control group, had the lowest.

The authors of the study described the rest of their findings: “Among patients with one or two Z alleles, two patients with lung and liver impairment showed the highest concentrations of CP (47.5 µg/mL), followed by those with only liver abnormality (n=6, CP=34 µg/mL), only lung (n=18, CP=26.5 µg/mL) and no abnormalities (n=23, CP=14.3 µg/mL).” This means that AATD patients with severe disease had higher levels of CP.

These findings demonstrated that CP concentrations are associated with the presence and severity of lung and liver disease in AATD patients. Therefore, CP can be used as a sort of prognostic indicator and may strengthen understanding of AATD pathophysiology through further research. 


Núñez A, Belmonte I, Miranda, E. et al. Association between circulating alpha-1 antitrypsin polymers and lung and liver diseaseRespir Res. Published online September 15, 2021. doi:10.1186/s12931-021-01842-5