1Antitrypsin

Alpha-1 antitrypsin (A1AT) is a liver-produced glycoprotein that functions as a serine protease inhibitor. It primarily inhibits neutrophil elastase in the lungs, protecting elastic tissue from proteolytic damage during inflammation. It belongs to the serpin superfamily and circulates in the bloodstream, reaching the lungs to limit tissue injury.

The SERPINA1 gene encodes A1AT. Most individuals have the normal PiMM genotype, but variants such as PiZ and PiS can reduce circulating A1AT levels or produce misfolded protein that accumulates in hepatocytes. Inheritance is codominant, meaning different alleles contribute to the phenotype. Severe deficiency results in markedly lower serum levels of A1AT.

Clinical significance of A1AT deficiency includes an increased risk of early-onset emphysema and chronic obstructive pulmonary disease, especially among smokers. Some genotypes may also lead to liver disease, including hepatitis and cirrhosis, due to accumulation of the abnormal protein in the liver.

Diagnosis typically involves measuring serum A1AT concentration and performing genetic testing to identify SERPINA1 variants. Lung function testing is used to assess respiratory impact, and imaging may be employed to evaluate emphysema.

Management focuses on reducing lung damage and preventing infections. This includes smoking cessation, vaccinations, and standard COPD therapies as indicated. In select adults with confirmed severe deficiency and established lung disease, augmentation therapy with intravenous purified human A1AT may slow the rate of lung function decline but is not curative. In rare cases of severe liver disease, liver transplantation may be considered.