The membrane voltage-gated proton channel-1 (HVCN1) is underexpressed in the neutrophils of people with alpha-1 antitrypsin deficiency (AATD), according to a new study published in Medicina. Treating AATD patients with alpha-1 antitrypsin (AAT) augmentation therapy increased expression of HVCN1 in the plasma membrane of neutrophils, the study also found.

Padraig Hawkins, PhD, from the Irish Centre for Genetic Lung Disease, Department of Medicine, Royal College of Surgeons in Dublin, and the coauthors of the study wrote, “Our findings further support the use of intravenous augmentation therapy in individuals with severe AATD and established lung disease.” 

AATD deficiency is a rare genetic disease affecting the liver and lungs. People with the disease have a high risk of early-onset emphysema, partly due to neutrophil-mediated lung destruction.

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HVCN1 is integrally linked to neutrophil function. Here, researchers examined the expression of the HVCN1 protein in AATD neutrophils to assess whether it was altered. They also investigated the ability of serum AAT to control HVCN1 expression.

First, they purified circulating neutrophils from the blood of 20 patients with AATD, 3 AATD patients receiving AAT augmentation therapy, and 20 healthy controls. 

The results showed that HVCN1 was underexpressed in the neutrophils of patients with AATD. In patients treated with AAT augmentation therapy, the expression of HVCN1 was increased in neutrophil plasma membranes.

Using a technique called fluorescence resonance energy transfer, the researchers also measured neutrophil membrane-bound elastase and “demonstrated that HVCN1 undergoes significant proteolytic degradation in activated neutrophils.”

They concluded that the reduced levels of HVCN1 in peripheral blood neutrophils may influence the neutrophil-dominated immune response in the airways of patients with AATD. This, they said, “highlights the role of antiprotease treatment and specifically AAT augmentation therapy in protecting neutrophil membrane expression of HVCN1.”


Hawkins P, Sya J, Hup NK, Murphy MP, McElvaney NG, Reeves EP. Alpha-1 antitrypsin augmentation inhibits proteolysis of neutrophil membrane voltage-gated proton channel-1 in alpha-1 deficient individuals. Medicina (Kaunas). 2021;57(8):814. doi:10.3390/medicina57080814