Researchers from the US and the UK have identified plasma biomarkers that are unique to and shared between alpha-1 antitrypsin deficiency (AATD) and chronic obstructive pulmonary disease (COPD).

The researchers also generated a protein score that is strongly associated with emphysema in patients with these 2 conditions. Finally, they identified unique biomarkers associated with diffusion capacity and emphysema in AATD patients who have the PiZZ genotype.

These findings can help stratify AATD carriers and patients with early disease who might be at higher risk of developing emphysema. AATD is the most common genetic cause of emphysema but with great phenotypic heterogeneity between patients, the cause of which is not understood. 


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In the present study, researchers led by Russell P. Bowler, MD, PhD, aimed to identify plasma biomarkers in patients with AATD and COPD, which could explain this heterogeneity.

The team analyzed the plasma or serum of 5924 patients from 4 AATD and COPD cohorts and tested the association between 4720 individual proteins or combined in a protein score with emphysema.

They found 2 unique proteins associated with lung density and 98 proteins associated with diffusion capacity in people with AATD who have the PiZZ genotype. Of these 98 proteins, 68 were also associated with diffusion capacity in people with COPD and were enriched for insulin-like growth factor, lipid droplet, and myosin complex.

People with the PiMZ genotype had similar proteins associated with diffusion capacity as people with COPD.

“Our emphysema protein score . . . predicted emphysema in AATD and COPD subjects,” the researchers wrote. 

The study is published in the journal eBioMedicine, which is part of The Lancet.

AATD deficiency is caused by a mutation in the SERPINA1 gene, which used to be called the Pi gene. The gene has different alleles—the normal one being called the M allele and 2 mutant alleles called the Z and S alleles.  

Reference

Serban KA, Pratte KA, Strange C, et al. Unique and shared systemic biomarkers for emphysema in alpha-1 antitrypsin deficiency and chronic obstructive pulmonary disease. EBioMedicine. Published online September 22, 2022. doi:10.1016/j.ebiom.2022.104262