Alpha1Antitrypsin

Alpha-1 antitrypsin (A1AT) is a serum protease inhibitor of the serpin family, mainly produced by the liver. Its principal function is to protect lung tissue from neutrophil elastase during inflammation, by circulating in the blood and diffusing into the airways to inhibit proteolysis.

Genetics: A1AT is encoded by the SERPINA1 gene on chromosome 14. Variants designated by letters such as M, S, and Z determine the amount and function of the protein. The Z variant causes misfolding and accumulation in hepatocytes, leading to low circulating levels. The ZZ genotype yields severe deficiency; MZ and SZ genotypes produce milder reductions. Inheritance is codominant, so both alleles influence risk.

Clinical significance: A deficiency increases the risk of early-onset emphysema, especially in smokers, and can be associated with liver disease due to hepatic retention of misfolded A1AT. Some infants and children may have liver involvement; adults may develop lung disease later in life.

Diagnosis: Suspected in individuals with COPD at a young age or a family history. Diagnosis relies on tests that measure serum A1AT levels and identify SERPINA1 variants (phenotype or genotype testing). Lung function tests and imaging assess respiratory disease; liver function tests evaluate hepatic involvement.

Management: There is no cure. Management emphasizes avoidance of lung irritants, smoking cessation, vaccination, bronchodilators, and pulmonary rehabilitation. Augmentation therapy, intravenous infusion of pooled human A1AT, is used in selected patients to raise serum levels and slow lung function decline. Severe liver disease follows standard hepatology care; liver transplantation is an option in extreme cases.